Identification of QTLs for arsenic accumulation in maize (Zea mays L. using a RIL population.

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Dong Ding

Full Text Available The Arsenic (As concentration in different tissues of maize was analyzed using a set of RIL populations derived from an elite hybrid, Nongda108. The results showed that the trend of As concentration in the four measured tissues was leaves>stems>bracts>kernels. Eleven QTLs for As concentration were detected in the four tissues. Three QTLs for As concentration in leaves were mapped on chromosomes 1, 5, and 8, respectively. For As concentration in the bracts, two QTLs were identified, with 9.61% and 10.03% phenotypic variance. For As concentration in the stems, three QTLs were detected with 8.24%, 14.86%, and 15.23% phenotypic variance. Three QTLs were identified for kernels on chromosomes 3, 5, and 7, respectively, with 10.73%, 8.52%, and 9.10% phenotypic variance. Only one common chromosomal region between SSR marker bnlg1811 and umc1243 was detected for QTLs qLAV1 and qSAC1. The results implied that the As accumulation in different tissues in maize was controlled by different molecular mechanism. The study demonstrated that maize could be a useful plant for phytoremediation of As-contaminated paddy soil, and the QTLs will be useful for selecting inbred lines and hybrids with low As concentration in their kernels.

Learning and motivation in the human striatum.

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Shohamy, Daphna

2011-06-01

The past decade has seen a dramatic change in our understanding of the role of the striatum in behavior. Early perspectives emphasized a role for the striatum in habitual learning of stimulus-response associations and sequences of actions. Recent advances from human neuroimaging research suggest a broader role for the striatum in motivated learning. New findings demonstrate that the striatum represents multiple learning signals and highlight the contribution of the striatum across many cognitive domains and contexts. Recent findings also emphasize interactions between the striatum and other specialized brain systems for learning. Together, these findings suggest that the striatum contributes to a distributed network that learns to select actions based on their predicted value in order to optimize behavior. Copyright © 2011 Elsevier Ltd. All rights reserved.

Analysis of QTLs for yield-related traits in Yuanjiang common wild rice (Oryza rufipogon Griff.).

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Fu, Qiang; Zhang, Peijiang; Tan, Lubin; Zhu, Zuofeng; Ma, Dan; Fu, Yongcai; Zhan, Xinchun; Cai, Hongwei; Sun, Chuanqing

2010-02-01

Using an accession of common wild rice (Oryza rufipogon Griff.) collected from Yuanjiang County, Yunnan Province, China, as the donor and an elite cultivar 93-11, widely used in two-line indica hybrid rice production in China, as the recurrent parent, an advanced backcross populations were developed. Through genotyping of 187 SSR markers and investigation of six yield-related traits of two generations (BC(4)F(2) and BC(4)F(4)), a total of 26 QTLs were detected by employing single point analysis and interval mapping in both generations. Of the 26 QTLs, the alleles of 10 (38.5%) QTLs originating from O. rufipogon had shown a beneficial effect for yield-related traits in the 93-11 genetic background. In addition, five QTLs controlling yield and its components were newly identified, indicating that there are potentially novel alleles in Yuanjiang common wild rice. Three regions underling significant QTLs for several yield-related traits were detected on chromosome 1, 7 and 12. The QTL clusters were founded and corresponding agronomic traits of those QTLs showed highly significant correlation, suggesting the pleiotropism or tight linkage. Fine-mapping and cloning of these yield-related QTLs from wild rice would be helpful to elucidating molecular mechanism of rice domestication and rice breeding in the future. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Mapping QTLs Controlling Flowering Time and Important Agronomic Traits in Pearl Millet.

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Kumar, Sushil; Hash, C Tom; Nepolean, T; Satyavathi, C Tara; Singh, Govind; Mahendrakar, Mahesh D; Yadav, Rattan S; Srivastava, Rakesh K

2017-01-01

Pearl millet [ Pennisetum glaucum (L.) R. Br.] is a staple crop for the people of arid and semi-arid regions of the world. It is fast gaining importance as a climate resilient nutricereal. Exploiting the bold seeded, semi-dwarf, and early flowering genotypes in pearl millet is a key breeding strategy to enhance yield, adaptability, and for adequate food in resource-poor zones. Genetic variation for agronomic traits of pearl millet inbreds can be used to dissect complex traits through quantitative trait locus (QTL) mapping. This study was undertaken to map a set of agronomically important traits like flowering time (FT), plant height (PH), panicle length (PL), and grain weight (self and open-pollinated seeds) in the recombinant inbred line (RIL) population of ICMB 841-P3 × 863B-P2 cross. Excluding grain weight (open pollinated), heritabilities for FT, PH, PL, grain weight (selfed) were in high to medium range. A total of six QTLs for FT were detected on five chromosomes, 13 QTLs for PH on six chromosomes, 11 QTLs for PL on five chromosomes, and 14 QTLs for 1,000-grain weight (TGW) spanning five chromosomes. One major QTL on LG3 was common for FT and PH. Three major QTLs for PL, one each on LG1, LG2, and LG6B were detected. The large effect QTL for TGW (self) on LG6B had a phenotypic variance ( R 2 ) of 62.1%. The R 2 for FT, TGW (self), and PL ranged from 22.3 to 59.4%. A total of 21 digenic interactions were discovered for FT ( R 2 = 18-40%) and PL ( R 2 = 13-19%). The epistatic effects did not reveal any significant QTL × QTL × environment (QQE) interactions. The mapped QTLs for flowering time and other agronomic traits in present experiment can be used for marker-assisted selection (MAS) and genomic selection (GS) breeding programs.

Localization of QTLs for in vitro plant regeneration in tomato.

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Trujillo-Moya, Carlos; Gisbert, Carmina; Vilanova, Santiago; Nuez, Fernando

2011-10-20

Low regeneration ability limits biotechnological breeding approaches. The influence of genotype in the regeneration response is high in both tomato and other important crops. Despite the various studies that have been carried out on regeneration genetics, little is known about the key genes involved in this process. The aim of this study was to localize the genetic factors affecting regeneration in tomato. We developed two mapping populations (F2 and BC1) derived from a previously selected tomato cultivar (cv. Anl27) with low regeneration ability and a high regeneration accession of the wild species Solanum pennellii (PE-47). The phenotypic assay indicated dominance for bud induction and additive effects for both the percentage of explants with shoots and the number of regenerated shoots per explant. Two linkage maps were developed and six QTLs were identified on five chromosomes (1, 3, 4, 7 and 8) in the BC1 population by means of the Interval Mapping and restricted Multiple QTL Mapping methods. These QTLs came from S. pennellii, with the exception of the minor QTL located on chromosome 8, which was provided by cv. Anl27. The main QTLs correspond to those detected on chromosomes 1 and 7. In the F2 population, a QTL on chromosome 7 was identified on a similar region as that detected in the BC1 population. Marker segregation distortion was observed in this population in those areas where the QTLs of BC1 were detected. Furthermore, we located two tomato candidate genes using a marker linked to the high regeneration gene: Rg-2 (a putative allele of Rg-1) and LESK1, which encodes a serine/threonine kinase and was proposed as a marker for regeneration competence. As a result, we located a putative allele of Rg-2 in the QTL detected on chromosome 3 that we named Rg-3. LESK1, which is also situated on chromosome 3, is outside Rg-3. In a preliminary exploration of the detected QTL peaks, we found several genes that may be related to regeneration. In this study we have

Localization of QTLs for in vitro plant regeneration in tomato

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Nuez Fernando

2011-10-01

Full Text Available Abstract Background Low regeneration ability limits biotechnological breeding approaches. The influence of genotype in the regeneration response is high in both tomato and other important crops. Despite the various studies that have been carried out on regeneration genetics, little is known about the key genes involved in this process. The aim of this study was to localize the genetic factors affecting regeneration in tomato. Results We developed two mapping populations (F2 and BC1 derived from a previously selected tomato cultivar (cv. Anl27 with low regeneration ability and a high regeneration accession of the wild species Solanum pennellii (PE-47. The phenotypic assay indicated dominance for bud induction and additive effects for both the percentage of explants with shoots and the number of regenerated shoots per explant. Two linkage maps were developed and six QTLs were identified on five chromosomes (1, 3, 4, 7 and 8 in the BC1 population by means of the Interval Mapping and restricted Multiple QTL Mapping methods. These QTLs came from S. pennellii, with the exception of the minor QTL located on chromosome 8, which was provided by cv. Anl27. The main QTLs correspond to those detected on chromosomes 1 and 7. In the F2 population, a QTL on chromosome 7 was identified on a similar region as that detected in the BC1 population. Marker segregation distortion was observed in this population in those areas where the QTLs of BC1 were detected. Furthermore, we located two tomato candidate genes using a marker linked to the high regeneration gene: Rg-2 (a putative allele of Rg-1 and LESK1, which encodes a serine/threonine kinase and was proposed as a marker for regeneration competence. As a result, we located a putative allele of Rg-2 in the QTL detected on chromosome 3 that we named Rg-3. LESK1, which is also situated on chromosome 3, is outside Rg-3. In a preliminary exploration of the detected QTL peaks, we found several genes that may be related

Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

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Adam M Wentzell

2007-09-01

Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

QTLs for tolerance of drought and breeding for tolerance of abiotic and biotic stress: an integrated approach.

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Shalabh Dixit

Full Text Available BACKGROUND: The coupling of biotic and abiotic stresses leads to high yield losses in rainfed rice (Oryza sativa L. growing areas. While several studies target these stresses independently, breeding strategies to combat multiple stresses seldom exist. This study reports an integrated strategy that combines QTL mapping and phenotypic selection to develop rice lines with high grain yield (GY under drought stress and non-stress conditions, and tolerance of rice blast. METHODOLOGY: A blast-tolerant BC2F3-derived population was developed from the cross of tropical japonica cultivar Moroberekan (blast- and drought-tolerant and high-yielding indica variety Swarna (blast- and drought-susceptible through phenotypic selection for blast tolerance at the BC2F2 generation. The population was studied for segregation distortion patterns and QTLs for GY under drought were identified along with study of epistatic interactions for the trait. RESULTS: Segregation distortion, in favour of Moroberekan, was observed at 50 of the 59 loci. Majority of these marker loci co-localized with known QTLs for blast tolerance or NBS-LRR disease resistance genes. Despite the presence of segregation distortion, high variation for DTF, PH and GY was observed and several QTLs were identified under drought stress and non-stress conditions for the three traits. Epistatic interactions were also detected for GY which explained a large proportion of phenotypic variance observed in the population. CONCLUSIONS: This strategy allowed us to identify QTLs for GY along with rapid development of high-yielding purelines tolerant to blast and drought with considerably reduced efforts. Apart from this, it also allowed us to study the effects of the selection cycle for blast tolerance. The developed lines were screened at IRRI and in the target environment, and drought and blast tolerant lines with high yield were identified. With tolerance to two major stresses and high yield potential, these

LOD score exclusion analyses for candidate QTLs using random population samples.

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Deng, Hong-Wen

2003-11-01

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.

Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

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Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

2017-11-01

The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

QTLs for resistance to Phomopsis seed decay are associated with days to maturity in soybean (Glycine max).

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Sun, Suli; Kim, Moon Young; Van, Kyujung; Lee, Yin-Won; Li, Baodu; Lee, Suk-Ha

2013-08-01

Phomopsis seed decay (PSD), primarily caused by Phomopsis longicolla, is a major contributor to poor soybean seed quality and significant yield loss, particularly in early maturing soybean genotypes. However, it is not yet known whether PSD resistance is associated with early maturity. This study was conducted to identify quantitative trait loci (QTLs) for resistance to PSD and days to maturity using a recombinant inbred line (RIL) population derived from a cross between the PSD-resistant Taekwangkong and the PSD-susceptible SS2-2. Based on a genetic linkage map incorporating 117 simple sequence repeat markers, QTL analysis revealed two and three QTLs conferring PSD resistance and days to maturity, respectively, in the RIL population. Two QTLs (PSD-6-1 and PSD-10-2) for PSD resistance were identified in the intervals of Satt100-Satt460 and Sat_038-Satt243 on chromosomes 6 and 10, respectively. Two QTLs explained phenotypic variances in PSD resistance of 46.3 and 14.1 %, respectively. At the PSD-6-1 QTL, the PSD-resistant cultivar Taekwangkong contributed the allele with negative effect decreasing the infection rate of PSD and this QTL does not overlap with any previously reported loci for PSD resistance in other soybean genotypes. Among the three QTLs for days to maturity, two (Mat-6-2 and Mat-10-3) were located at positions similar to the PSD-resistance QTLs. The identification of the QTLs linked to both PSD resistance and days to maturity indicates a biological correlation between these two traits. The newly identified QTL for resistance to PSD associated with days to maturity in Taekwangkong will help improve soybean resistance to P. longicolla.

Three QTLs for Botrytis cinerea resistance in tomato

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Finkers, H.J.; Berg, van den P.M.M.M.; Berloo, van R.; Have, ten A.; Heusden, van A.W.; Kan, van J.A.L.; Lindhout, P.

2007-01-01

Tomato (Solanum lycopersicum) is susceptible to grey mold (Botrytis cinerea). Partial resistance to this fungus was identified in accessions of wild relatives of tomato such as S. habrochaites LYC4. In order to identify loci involved in quantitative resistance (QTLs) to B. cinerea, a population of

Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

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Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment Pmediator based on Sobel Pmediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530

Lung eQTLs to help reveal the molecular underpinnings of asthma.

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Ke Hao

Full Text Available Genome-wide association studies (GWAS have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151. The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases.

Both epistatic and additive effects of QTLs are involved in polygenic induced resistance to disease: a case study, the interaction pepper - Phytophthora capsici Leonian.

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Lefebvre, V; Palloix, A

1996-09-01

To study the resistance of pepper to Phytophthora capsici, we analyzed 94 doubled-haploid (DH) lines derived from the intraspecific F1 hybrid obtained from a cross between Perennial, an Indian pungent resistant line, and Yolo Wonder, an American bell-pepper susceptible line, with 119 DNA markers. Four different criteria were used to evaluate the resistance, corresponding to different steps or mechanisms of the host-pathogen interaction: root-rot index, receptivity, inducibility and stability. Three distinct ANOVA models between DNA marker genotypes and the four disease criteria identified 13 genomic regions, distributed across several linkage groups or unlinked markers, affecting the resistance of pepper to P. capsici. Some QTLs were criterion specific, whereas others affect several criteria, so that the four resistance criteria were controlled by different combinations of QTLs. The QTLs were very different in their quantitative effect (R(2) values), including major QTLs which explained 41-55% of the phenotypic variance, intermediate QTLs with additive or/and epistatic action (17-28% of the variance explained) and minor QTLs. Favourable alleles of some minor QTLs were carried in the susceptible parent. The total phenotypic variation accounted for by QTLs reached up to 90% for receptivity, with an important part due to epistasis effects between QTLs (with or without additive effects). The relative impact of resistance QTLs in disease response is discussed.

Meta-Analyses of QTLs Associated with Protein and Oil Contents and Compositions in Soybean [Glycine max (L.) Merr.] Seed.

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Van, Kyujung; McHale, Leah K

2017-06-01

Soybean [ Glycine max (L.) Merr.] is a valuable and nutritious crop in part due to the high protein meal and vegetable oil produced from its seed. Soybean producers desire cultivars with both elevated seed protein and oil concentrations as well as specific amino acid and fatty acid profiles. Numerous studies have identified quantitative trait loci (QTLs) associated with seed composition traits, but validation of these QTLs has rarely been carried out. In this study, we have collected information, including genetic location and additive effects, on each QTL for seed contents of protein and oil, as well as amino acid and fatty acid compositions from over 80 studies. Using BioMercator V. 4.2, a meta-QTL analysis was performed with genetic information comprised of 175 QTLs for protein, 205 QTLs for oil, 156 QTLs for amino acids, and 113 QTLs for fatty acids. A total of 55 meta-QTL for seed composition were detected on 6 out of 20 chromosomes. Meta-QTL possessed narrower confidence intervals than the original QTL and candidate genes were identified within each meta-QTL. These candidate genes elucidate potential natural genetic variation in genes contributing to protein and oil biosynthesis and accumulation, providing meaningful information to further soybean breeding programs.

Identification of QTLs Associated to Plant Architecture in Cassava (Manihot esculenta

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Camilo López

2016-01-01

Full Text Available La yuca (Manihot esculenta es el cuarto cultivo en importancia a nivel mundial como fuente de calorías para la población humana después del arroz, el azúcar y el maíz, posicionándose por esta razón como un cultivo primordial para la seguridad alimentaria. Su arquitectura ha sido considerada como un factor clave que subyace a la fisiología del rendimiento, relacionando características morfológicas con productividad. En este trabajo se evaluaron diferentes características de arquitectura vegetal en yuca. Los caracteres fueron evaluados en una población F1 compuesta por 133 hermanos completos (familia K sembrados en dos lugares biogeográficamente diferentes: La Vega (Cundinamarca y Arauca (Arauca en Colombia. Las características evaluadas relacionadas con la arquitectura vegetal fueron altura de la planta (AT, número de brotes (NB, longitud entrenudos (LE, número de raíces (NR, peso de raíces (PR, pigmentación del peciolo (PP, área de la hoja (AH y tipo de hoja (TH. A partir de los datos obtenidos y empleando un mapa genético de alta densidad basado en SNPs (Single Nucleotide Polymorphisms se llevó a cabo un análisis de QTLs (Quantitative Trait Loci. Se lograron identificar tres QTLs para La Vega asociados con los caracteres altura total, número de brotes y área de la hoja. Para Arauca se detectaron tres QTLs asociados con altura total, longitud de entrenudos y número de brotes. Los QTLs se distribuyeron en cuatro grupos de ligamiento y explicaron entre 18,93 y 41,92 % de la variación genética.

Molecular Mapping of QTLs for Yield and Yield-Related Traits in Oryza sativa cv Swarna × O. nivara (IRGC81848 Backcross Population

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B.P. MALLIKARJUNA SWAMY

2011-09-01

Full Text Available Advanced backcross QTL analysis was used to identify QTLs for seven yield and yield-related traits in a BC2F2 population from the cross between a popular Oryza sativa cv Swarna and O. nivara IRGC81848. Transgressive segregants with more than 15% increased effect over Swarna were observed for all the traits except days to heading and days to 50% flowering. Thirty QTLs were detected for seven yield and yield-related traits using interval and composite interval mapping. Enhancing alleles at 13 (45% of these QTLs were derived from O. nivara, and enhancing alleles at all the QTLs for stem diameter and rachis diameter were derived from O. nivara. Three stem diameter QTLs, two rachis diameter QTLs and one number of secondary branches QTL identified by both Interval and composite interval mapping contributed more than 15% of the total phenotypic variance. The QTL epistasis was significant for stem diameter and plot yield. The most significant QTLs qSD7.2, qSD8.1 and qSD9.1 for stem diameter, qRD9.1 for rachis diameter and qNSB1.1 for number of secondary branches are good targets to evaluate their use in marker-assisted selection. O. nivara is a good source of novel alleles for yield related traits and reveals major effect QTLs suitable for marker-assisted selection.

Discovery of Consistent QTLs of Wheat Spike-Related Traits under Nitrogen Treatment at Different Development Stages

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Zhiying Deng

2017-12-01

Full Text Available Spike-related traits such as spike length (Sl, fertile spikelet number (Fsn, sterile spikelet number (Ssn, grain number per spike (Gns, and thousand-kernel weight (Tkw are important factors influencing wheat yield. However, reliably stable markers that can be used for molecular breeding in different environments have not yet been identified. In this study, a double haploid (DH population was used for quantitative trait locus (QTL mapping of five spike-related traits under four different nitrogen (N supply dates in two locations and years. Seventy additive QTLs with phenotypic variation ranging from 4.12 to 34.74% and 10 major epistatic QTLs were identified. Eight important chromosomal regions on five chromosomes (1B, 2B, 2D, 5D, and 6A were found. Sixteen stable QTLs were detected for which N application had little effect. Among those stable QTLs, QSl.sdau-2D-1, and QSl.sdau-2D-2, with phenotypic variation explained (PVE of 10.4 and 24.2%, respectively, were flanked by markers Xwmc112 and Xcfd53 in the same order. The QTLs QSsn.sdau-2B-1, QFsn.sdau-2B-1, and QGns.sdau-2B, with PVE ranging from 4.37 to 28.43%, collocated in the Xwmc179-Xbarc373 marker interval. The consistent kernel wheat QTL (QTkw.sdau-6A on the long arm of chromosome 6A, flanked by SSR markers Xbarc1055 and Xwmc553, showed PVE of 5.87–15.18%. Among these stable QTLs, the two flanking markers Xwmc112 and Xcfd53 have been validated using different varieties and populations for selecting Sl. Therefore, these results will be of great value for marker-assisted selection (MAS in breeding programs and will accelerate the understanding of the genetic relationships among spike-related traits at the molecular level.

Discovery of Consistent QTLs of Wheat Spike-Related Traits under Nitrogen Treatment at Different Development Stages.

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Deng, Zhiying; Cui, Yong; Han, Qingdian; Fang, Wenqi; Li, Jifa; Tian, Jichun

2017-01-01

Spike-related traits such as spike length (Sl), fertile spikelet number (Fsn), sterile spikelet number (Ssn), grain number per spike (Gns), and thousand-kernel weight (Tkw) are important factors influencing wheat yield. However, reliably stable markers that can be used for molecular breeding in different environments have not yet been identified. In this study, a double haploid (DH) population was used for quantitative trait locus (QTL) mapping of five spike-related traits under four different nitrogen (N) supply dates in two locations and years. Seventy additive QTLs with phenotypic variation ranging from 4.12 to 34.74% and 10 major epistatic QTLs were identified. Eight important chromosomal regions on five chromosomes (1B, 2B, 2D, 5D, and 6A) were found. Sixteen stable QTLs were detected for which N application had little effect. Among those stable QTLs, QSl.sdau-2D-1 , and QSl.sdau-2D-2 , with phenotypic variation explained (PVE) of 10.4 and 24.2%, respectively, were flanked by markers Xwmc112 and Xcfd53 in the same order. The QTLs QSsn.sdau-2B-1, QFsn.sdau-2B-1 , and QGns.sdau-2B , with PVE ranging from 4.37 to 28.43%, collocated in the Xwmc179 - Xbarc373 marker interval. The consistent kernel wheat QTL ( QTkw.sdau-6A ) on the long arm of chromosome 6A, flanked by SSR markers Xbarc1055 and Xwmc553 , showed PVE of 5.87-15.18%. Among these stable QTLs, the two flanking markers Xwmc112 and Xcfd53 have been validated using different varieties and populations for selecting Sl. Therefore, these results will be of great value for marker-assisted selection (MAS) in breeding programs and will accelerate the understanding of the genetic relationships among spike-related traits at the molecular level.

Quantitative Imaging of Cholinergic Interneurons Reveals a Distinctive Spatial Organization and a Functional Gradient across the Mouse Striatum.

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Miriam Matamales

Full Text Available Information processing in the striatum requires the postsynaptic integration of glutamatergic and dopaminergic signals, which are then relayed to the output nuclei of the basal ganglia to influence behavior. Although cellularly homogeneous in appearance, the striatum contains several rare interneuron populations which tightly modulate striatal function. Of these, cholinergic interneurons (CINs have been recently shown to play a critical role in the control of reward-related learning; however how the striatal cholinergic network is functionally organized at the mesoscopic level and the way this organization influences striatal function remains poorly understood. Here, we systematically mapped and digitally reconstructed the entire ensemble of CINs in the mouse striatum and quantitatively assessed differences in densities, spatial arrangement and neuropil content across striatal functional territories. This approach demonstrated that the rostral portion of the striatum contained a higher concentration of CINs than the caudal striatum and that the cholinergic content in the core of the ventral striatum was significantly lower than in the rest of the regions. Additionally, statistical comparison of spatial point patterns in the striatal cholinergic ensemble revealed that only a minor portion of CINs (17% aggregated into cluster and that they were predominantly organized in a random fashion. Furthermore, we used a fluorescence reporter to estimate the activity of over two thousand CINs in naïve mice and found that there was a decreasing gradient of CIN overall function along the dorsomedial-to-ventrolateral axis, which appeared to be independent of their propensity to aggregate within the striatum. Altogether this work suggests that the regulation of striatal function by acetylcholine across the striatum is highly heterogeneous, and that signals originating in external afferent systems may be principally determining the function of CINs in the

Development of molecular map and identification of QTLs linked to ...

Indian Academy of Sciences (India)

2015-12-01

Dec 1, 2015 ... Five major quantitative trait loci (QTLs) were detected in both seasons for ... Journal of Genetics, Vol. ... QTL analysis was performed using QTL Cartographer ..... (DST), New Delhi, for the financial support (GrantPS-170/2010).

Detection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling

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Taylor, B.A.; Phillips, S.J. [Jackson Lab., Bar Harbor, ME (United States)

1996-06-15

The inheritance of obesity has been analyzed in an intercross between the lean 129/Sv mouse strain and the obesity-prone EL/Suz mouse strain. The weights of three major fat pads were determined on 4-month-old mice, and the sum of these weights, divided by body weight, was used as an adiposity index. The strategy of selective DNA pooling was used as a primary screen to identify putative quantitative trait loci (QTLs) affecting adiposity index. DNA pools representing the leanest 15% and fattest 15% of the F2 progeny were compared for differential allelic enrichment using widely dispersed microsatellite variants. To evaluate putative QTLs, individual genotyping and interval mapping were employed to estimate QTL effects and assess statistical significance. One QTL affecting adiposity index, which accounted for 12.3% of phenotypic variance in gender-merged data, was mapped to the central region of Chromosome (Chr) 7. The QTL allele inherited from EL conferred increased adiposity. A second QTL that accounts for 6.3% of phenotypic variance was identified on Chr 1 near D1Mitt211. At both QTLs, the data are consistent with dominant inheritance of the allele contributing to obesity. The possible relationships between these QTLs and previously described obesity QYLs, major obesity mutations, and candidate genes are discussed. 42 refs., 3 figs., 3 tabs.

Genetic mapping of quantitative trait loci (QTLs) with effects on ...

African Journals Online (AJOL)

SERVER

2008-02-05

Feb 5, 2008 ... This paper reports on the development of a genetic ... RILs along with the two parental lines were evaluated in the screen- .... A genetic linkage map of cowpea showing the QTLs (in green) that is associated with the resistance.

Detection of QTLs for seedling characteristics in barley (Hordeum vulgare L.) grown under hydroponic culture condition.

Science.gov (United States)

Wang, Qifei; Sun, Genlou; Ren, Xifeng; Wang, Jibin; Du, Binbin; Li, Chengdao; Sun, Dongfa

2017-11-07

Seedling characteristics play significant roles in the growth and development of barley (Hordeum vulgare L.), including stable stand establishment, water and nutrients uptake, biotic resistance and abiotic stresses, and can influence yield and quality. However, the genetic mechanisms underlying seedling characteristics in barley are largely unknown and little research has been done. In the present work, 21 seedling-related characteristics are assessed in a barley double haploid (DH) population, grown under hydroponic conditions. Of them, leaf age (LAG), shoot height (SH), maximum root length (MRL), main root number (MRN) and seedling fresh weight (SFW) were investigated at the 13th, 20th, 27th, and 34th day after germination. The objectives were to identify quantitative trait loci (QTLs) underlying these seedling characteristics using a high-density linkage map and to reveal the QTL expression pattern by comparing the QTLs among four different seedling growth stages. A total of 70 QTLs were distributed over all chromosomes except 4H, and, individually, accounted for 5.01%-77.78% of phenotypic variation. Out of the 70 detected QTLs, 23 showed a major effect on 14 seedling-related characteristics. Ten co-localized chromosomal regions on 2H (five regions), 3H (two regions) and 7H (three regions) involved 39 QTLs (55.71%), each simultaneously influenced more than one trait. Meanwhile, 9 co-localized genomic regions involving 22 QTLs for five seedling characteristics (LAG, SH, MRL, MRN and SFW) at the 13th, 20th, 27th and 34th day-old seedling were common for two or more growth stages of seedling. QTL in the vicinity of Vrs1 locus on chromosome 2H with the favorable alleles from Huadamai 6 was found to have the largest main effects on multiple seedling-related traits. Six QTL cluster regions associated with 16 seedling-related characteristics were observed on chromosome 2H, 3H and 7H. The majority of the 29 regions identified for five seedling characteristics were

Earliness per se QTLs and their interaction with the photoperiod insensitive allele Ppd-D1a in the Cutler × AC Barrie spring wheat population.

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Kamran, A; Iqbal, M; Navabi, A; Randhawa, H; Pozniak, C; Spaner, D

2013-08-01

Earliness per se regulates flowering time independent of environmental signals and helps to fine tune the time of flowering and maturity. In this study, we aimed to map earliness per se quantitative trait loci (QTLs) affecting days to flowering and maturity in a population developed by crossing two spring wheat cultivars, Cutler and AC Barrie. The population of 177 recombinant inbred lines (RILs) was genotyped for a total of 488 SSR and DArT polymorphic markers on all 21 chromosomes. Three QTLs of earliness per se affecting days to flowering and maturity were mapped on chromosomes 1B (QEps.dms-1B1 and QEps.dms-1B2) and 5B (QEps.dms-5B1), in individual environments and when all the environments were combined. A QTL affecting flowering time (QFlt.dms-4A1) was identified on chromosome 4A. Two grain yield QTLs were mapped on chromosome 5B, while one QTL was mapped on chromosome 1D. The population segregated for the photoperiod insensitive gene, Ppd-D1a, and it induced earlier flowering by 0.69 days and maturity by 1.28 days. The photoperiod insensitive allele Ppd-D1a interacted in an additive fashion with QTLs for flowering and maturity times. The earliness per se QTL QFlt.dms-5B.1 inducing earlier flowering could help to elongate grain filling duration for higher grain yield. Hence, chromosome 5B possesses promising genomic regions that may be introgressed for higher grain yield with earlier maturity through marker-assisted selection in bread wheat.

QTLs Analysis and Validation for Fiber Quality Traits Using Maternal Backcross Population in Upland Cotton

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Lingling Ma

2017-12-01

Full Text Available Cotton fiber is renewable natural fiber source for textile. Improving fiber quality is an essential goal for cotton breeding project. In present study, F14 recombinant inbred line (RIL population was backcrossed by the maternal parent to obtain a backcross (BC population, derived from one Upland cotton hybrid. Three repetitive field trials were performed by randomized complete block design with two replicates in three locations in 2015, together with the BC population, common male parent and the RIL population. Totally, 26 QTLs in BC population explained 5.00–14.17% of phenotype variation (PV and 37 quantitative trait loci (QTL were detected in RIL population explaining 5.13–34.00% of PV. Seven common QTLs detected simultaneously in two populations explained PV from 7.69 to 23.05%. A total of 20 QTLs in present study verified the previous results across three environments in 2012. Particularly, qFL-Chr5-2 controlling fiber length on chromosome 5 explained 34.00% of PV, while qFL-Chr5-3 only within a 0.8 cM interval explained 13.93% of PV on average in multiple environments. These stable QTLs explaining great variation offered essential information for marker-assisted selection (MAS to improve fiber quality traits. Lots of epistasis being detected in both populations acted as one of important genetic compositions of fiber quality traits.

QTLs Analysis and Validation for Fiber Quality Traits Using Maternal Backcross Population in Upland Cotton.

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Ma, Lingling; Zhao, Yanpeng; Wang, Yumei; Shang, Lianguang; Hua, Jinping

2017-01-01

Cotton fiber is renewable natural fiber source for textile. Improving fiber quality is an essential goal for cotton breeding project. In present study, F 14 recombinant inbred line (RIL) population was backcrossed by the maternal parent to obtain a backcross (BC) population, derived from one Upland cotton hybrid. Three repetitive field trials were performed by randomized complete block design with two replicates in three locations in 2015, together with the BC population, common male parent and the RIL population. Totally, 26 QTLs in BC population explained 5.00-14.17% of phenotype variation (PV) and 37 quantitative trait loci (QTL) were detected in RIL population explaining 5.13-34.00% of PV. Seven common QTLs detected simultaneously in two populations explained PV from 7.69 to 23.05%. A total of 20 QTLs in present study verified the previous results across three environments in 2012. Particularly, qFL-Chr5-2 controlling fiber length on chromosome 5 explained 34.00% of PV, while qFL-Chr5-3 only within a 0.8 cM interval explained 13.93% of PV on average in multiple environments. These stable QTLs explaining great variation offered essential information for marker-assisted selection (MAS) to improve fiber quality traits. Lots of epistasis being detected in both populations acted as one of important genetic compositions of fiber quality traits.

Contributions of Hippocampus and Striatum to Memory-Guided Behavior Depend on Past Experience

Science.gov (United States)

2016-01-01

The hippocampal and striatal memory systems are thought to operate independently and in parallel in supporting cognitive memory and habits, respectively. Much of the evidence for this principle comes from double dissociation data, in which damage to brain structure A causes deficits in Task 1 but not Task 2, whereas damage to structure B produces the reverse pattern of effects. Typically, animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals concurrently learn two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue–response task (sequential training), whereas a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM), or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the sequential training condition also acquired the novel “other” task. When rats learned one task, HPC and DSL selectively supported spatial navigation and cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. Thus, in certain conditions, the hippocampal and striatal memory systems can operate cooperatively and in synergism. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue–response task facilitated subsequent spatial learning, whereas experience with spatial navigation delayed both concurrent and subsequent response learning. These findings suggest that there are multiple operational principles that govern memory networks. SIGNIFICANCE STATEMENT Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate

The dorsal striatum and ventral striatum play different roles in the programming of social behaviour: a tribute to Lex Cools.

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van den Bos, Ruud

2015-02-01

Early work by Lex Cools suggested that the caudate nucleus (dorsal striatum) plays a role in programming social behaviour: enhanced activity in the caudate nucleus increased the extent to which ongoing behaviour is controlled by the individual's own behaviour (internal control) rather than by that of its partners (external control). Interestingly, later studies by others have indicated that the ventral striatum plays a role in external rather than internal control. Here, I discuss the role of these different striatal areas - and the emotional (ventral striatum) and cognitive control (dorsal striatum) system in which they are embedded - in the organization of social behaviour in the context of locus of control. Following on from this discussion, I will pay particular attention to individual differences in social behaviour (individuals with more internal or external control), focusing on the role of dopamine, serotonin and the effects of stress-related challenges in relation to their different position in a dominance hierarchy. I will subsequently allude to potential psychological and behavioural problems in the social domain following on from these differences in locus of control ['social obliviousness' (dorsal stratum) and 'social impulsivity' (ventral striatum)]. In doing so, I provide as a tribute a historical account of the early research by Lex Cools.

Mapping of genes for flower-related traits and QTLs for flowering ...

Indian Academy of Sciences (India)

Mapping of genes for flower-related traits and QTLs for flowering time ... which would greatly enhance the use of G. darwinii-specific desirable genes in ... used to determine all linkage groups, the order of groups on the same ... age groups.

Mapping QTLs controlling kernel dimensions in a wheat inter-varietal RIL mapping population.

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Cheng, Ruiru; Kong, Zhongxin; Zhang, Liwei; Xie, Quan; Jia, Haiyan; Yu, Dong; Huang, Yulong; Ma, Zhengqiang

2017-07-01

Seven kernel dimension QTLs were identified in wheat, and kernel thickness was found to be the most important dimension for grain weight improvement. Kernel morphology and weight of wheat (Triticum aestivum L.) affect both yield and quality; however, the genetic basis of these traits and their interactions has not been fully understood. In this study, to investigate the genetic factors affecting kernel morphology and the association of kernel morphology traits with kernel weight, kernel length (KL), width (KW) and thickness (KT) were evaluated, together with hundred-grain weight (HGW), in a recombinant inbred line population derived from Nanda2419 × Wangshuibai, with data from five trials (two different locations over 3 years). The results showed that HGW was more closely correlated with KT and KW than with KL. A whole genome scan revealed four QTLs for KL, one for KW and two for KT, distributed on five different chromosomes. Of them, QKl.nau-2D for KL, and QKt.nau-4B and QKt.nau-5A for KT were newly identified major QTLs for the respective traits, explaining up to 32.6 and 41.5% of the phenotypic variations, respectively. Increase of KW and KT and reduction of KL/KT and KW/KT ratios always resulted in significant higher grain weight. Lines combining the Nanda 2419 alleles of the 4B and 5A intervals had wider, thicker, rounder kernels and a 14% higher grain weight in the genotype-based analysis. A strong, negative linear relationship of the KW/KT ratio with grain weight was observed. It thus appears that kernel thickness is the most important kernel dimension factor in wheat improvement for higher yield. Mapping and marker identification of the kernel dimension-related QTLs definitely help realize the breeding goals.

Identification of SSR and RAPD markers associated with QTLs of ...

African Journals Online (AJOL)

SERVER

2008-04-03

Apr 3, 2008 ... Parents and. F3 families had significant differences in studied traits (p ≤. 0.01). In this study, SSR and RAPD markers were used together for constructing linkage groups and rescanning the genome of rapeseed to identify QTLs controlling winter survival and related traits. For this, the parental polymorphism ...

Mapping and validation of QTLs for cold tolerance at seedling stage in rice from an indica cultivar Habiganj Boro VI (Hbj.BVI).

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Biswas, Partha S; Khatun, Hasina; Das, Nomita; Sarker, Md Mahathir; Anisuzzaman, M

2017-12-01

Yellowing, stunting, and seedling death associated with cold stress is a common problem in many Asian countries for winter rice cultivation. Improvement of cultivars through marker-assisted selection of QTLs for cold tolerance at seedling stage from locally adapted germplasm/cultivar is the most effective and sustainable strategy to resolve this problem. A study was undertaken to map QTLs from 151 F 2:3 progenies of a cross between a cold susceptible variety, BR1 and a locally adapted traditional indica cultivar, Hbj.BVI. A total of six significant QTLs were identified for two cold tolerance indices-cold-induced leaf discoloration and survival rate after a recovery period of seven days on chromosomes 6, 8, 11, and 12. Among these QTLs, qCTSL - 8 - 1 and qCTSS - 8 - 1 being co-localized into RM7027-RM339 on chromosome 8 and qCTSL - 12 - 1 and qCTSS - 12 - 1 into RM247-RM2529 on chromosome 12 showed 12.78 and 14.96% contribution, respectively, to the total phenotypic variation for cold tolerance. Validation of QTL effect in BC 1 F 3 population derived a cross between a cold susceptible BRRI dhan28 and Hbj.BVI showed dominating effect of qCTSL - 12 - 1 on cold tolerance at seedling stage and it became stronger when one or more other QTLs were co-segregated with it. These results suggest that the QTLs identified in this study are stable and effective on other genetic background also, which warrant the use of these QTLs for further study aiming to cultivar development for seedling stage cold tolerance.

Identification of SSR and RAPD markers associated with QTLs of ...

African Journals Online (AJOL)

Because of importance of winter survival in winter type of Brassica napus, this study was performed to identify the QTLs controlling winter survival and related traits using SSR and RAPD markers. For this, an F2:3 population of 200 families derived from crossing between cv. 'SLMO46' (winter type and cold resistant) and cv.

Mapping of QTLs for Leaf Malondialdehyde Content Associated with Stress Tolerance in Rice

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Jing JIANG

2009-03-01

Full Text Available Malondialdehyde (MDA is the final product of lipid peroxidation, and MDA content can reflect the stress tolerance of plants. To map QTLs conditioning the MDA content in rice leaves, a recombinant inbred line (RIL population with 247 lines derived from an indica-indica cross Zhenshan 97B×Milyang 46, and a linkage map consisting of 207 DNA markers were used. The RIL population showed a transgressive segregation in the MDA content of rice leaves. Two QTLs for the MDA content in rice leaves were detected in the intervals RG532–RG811 and RG381–RG236 on chromosome 1, with the additive effects from maternal and paternal parents, accounting for 4.33% and 4.62% of phenotype variations, respectively.

Mapeamento de QTLs para reação ao oídio e mancha-angular do feijoeiro-comum em diferentes locais

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Melo Leonardo Cunha

2002-01-01

Full Text Available Os objetivos deste trabalho foram mapear, em diferentes locais, marcadores RAPD ligados a QTLs (Quantitative Trait Loci de reação do feijoeiro-comum ao oídio e à mancha-angular, avaliar a interação de QTLs por locais e comparar os métodos de mapeamento e regressão múltipla no processo de detecção de QTLs. Foram avaliadas 196 linhagens recombinantes, oriundas do cruzamento entre as cultivares Carioca e Flor de Mayo, em duas épocas de cultivo: época da seca, para mancha-angular, e inverno para oídio, nos anos de 1996, 1997 e 1998, em dois locais de Minas Gerais. Foram conduzidos sete experimentos de avaliação fenotípica utilizando o delineamento experimental em látice quadrado simples. Os resultados mostraram que a interação QTLs por locais foi significativa, mas foram identificados alguns QTLs com maior estabilidade. O método da regressão múltipla detectou maior número de marcadores ligados a QTLs do que o processo de mapeamento por intervalo composto; não houve concordância entre os resultados apresentados pelos dois métodos. Os marcadores que se mostraram mais estáveis e promissores para serem utilizados em programas de seleção assistida foram OPR02-832, OPD08-759 e OPN10-851 para reação a oídio; OPN02-436, e OPN07-1072 para reação à mancha-angular.

Functional connectivity of the dorsal striatum in female musicians

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Shoji eTanaka

2016-04-01

Full Text Available The dorsal striatum (caudate/putamen is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians.Resting state functional magnetic resonance imaging (fMRI data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to graph theoretical analysis and functional connectivity analysis. The graph theoretical analysis of the entire brain revealed that the degree, which represents the number of connections, of the bilateral putamen was significantly lower in musicians than in nonmusicians. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum and between the left caudate nucleus and cerebellum. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum, with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers. To the best of our knowledge, this is the first study suggesting that long-term musical training results in a less extensive or selective functional network of the dorsal striatum.

Neurochemical characterization of the tree shrew dorsal striatum

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MATTHEW W RICE

2011-08-01

Full Text Available The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington's, Tourette's syndrome, obsessive-compulsive disorders and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei, which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase and acetylcholinesterase immunohistochemistry, and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum.

Genetic mapping of QTLs associated with seed macronutrients accumulation in 'MD96-5722' by 'Spencer' recombinant inbred lines of soybean

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Research of genetic mapping of QTLs for macronutrient accumulation in soybean seed is limited. Therefore, the objective of this research was to identify QTLs related to macronutrients (N, C, S, P, K, Ca, and Mg) in seeds in 92 F5:7 recombinant inbred lines developed from a cross between MD 96-5722 (...

Separate populations of neurons in ventral striatum encode value and motivation.

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Bissonette, Gregory B; Burton, Amanda C; Gentry, Ronny N; Goldstein, Brandon L; Hearn, Taylor N; Barnett, Brian R; Kashtelyan, Vadim; Roesch, Matthew R

2013-01-01

Neurons in the ventral striatum (VS) fire to cues that predict differently valued rewards. It is unclear whether this activity represents the value associated with the expected reward or the level of motivation induced by reward anticipation. To distinguish between the two, we trained rats on a task in which we varied value independently from motivation by manipulating the size of the reward expected on correct trials and the threat of punishment expected upon errors. We found that separate populations of neurons in VS encode expected value and motivation.

Goal- and retrieval-dependent activity in the striatum during memory recognition.

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Clos, Mareike; Schwarze, Ulrike; Gluth, Sebastian; Bunzeck, Nico; Sommer, Tobias

2015-06-01

The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions. To examine whether striatal activity during memory recognition reflects subjective value indeed, we conducted an fMRI study using a recognition memory paradigm in which the participants rated not only the recognition confidence but also indicated the pleasantness associated with the previous memory retrieval. The results demonstrated a high positive correlation between confidence and pleasantness both on the behavioral and brain activation level particularly in the striatum. As almost all of variance in the striatal confidence signal could be explained by experienced pleasantness, this part of the striatal memory recognition response probably corresponds to greater subjective value of high confidence responses. While perceived oldness was also strongly correlated with striatal activity, this activation pattern was clearly distinct from that associated with confidence and pleasantness and thus could not be explained by higher subjective value to detect "old" items. Together, these results show that at least two independent processes contribute to striatal activation in recognition memory: a more flexible evaluation response dependent on context and goals captured by memory confidence and a potentially retrieval-related response captured by perceived oldness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detection of elevated CO2 responsive QTLs for yield and its ...

African Journals Online (AJOL)

STORAGESEVER

2008-06-03

Jun 3, 2008 ... ... of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China. Accepted 12 May, 2008. A mapping population of IR24 (indica) chromosome segment substitution lines (CSSLs.) in Asominori. (japonica) background was used to detect quantitative trait loci (QTLs) for response to elevated CO2 in.

Mapping of QTLs for frost tolerance and heading time using SSR ...

African Journals Online (AJOL)

Selection for complex genetic traits, such as frost tolerance, can be simplified in plant breeding programs when linked markers were detected. The use of microsatellite markers for tagging and mapping important genes or QTLs is a goal in wheat genetic projects. In this study, 200 microsatellite markers were studied and ...

Construction of a SSR-Based Genetic Map and Identification of QTLs for Catechins Content in Tea Plant (Camellia sinensis)

Science.gov (United States)

Ma, Chun-Lei; Wang, Xin-Chao; Jin, Ji-Qiang; Wang, Xue-Min; Chen, Liang

2014-01-01

Catechins are the most important bioactive compounds in tea, and have been demonstrated to possess a wide variety of pharmacological activities. To characterize quantitative trait loci (QTLs) for catechins content in the tender shoots of tea plant, we constructed a moderately saturated genetic map using 406 simple sequence repeat (SSR) markers, based on a pseudo-testcross population of 183 individuals derived from an intraspecific cross of two Camellia sinensis varieties with diverse catechins composition. The map consisted of fifteen linkage groups (LGs), corresponding to the haploid chromosome number of tea plant (2n = 2x = 30). The total map length was 1,143.5 cM, with an average locus spacing of 2.9 cM. A total of 25 QTLs associated with catechins content were identified over two measurement years. Of these, nine stable QTLs were validated across years, and clustered into four main chromosome regions on LG03, LG11, LG12 and LG15. The population variability explained by each QTL was predominantly at moderate-to-high levels and ranged from 2.4% to 71.0%, with an average of 17.7%. The total number of QTL for each trait varied from four to eight, while the total population variability explained by all QTLs for a trait ranged between 38.4% and 79.7%. This is the first report on the identification of QTL for catechins content in tea plant. The results of this study provide a foundation for further cloning and functional characterization of catechin QTLs for utilization in improvement of tea plant. PMID:24676054

Urethritis due to corynebacterium striatum: An emerging germ.

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Frikh, Mohammed; El Yaagoubi, Imad; Lemnouer, Abdelhay; Elouennass, Mostafa

2015-01-01

Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is part of mucous and skin flora. It has been considered as a causative agent of many infections in intensive care, neurology, traumatology and urology, but was never implicated in non-gonococcal urethritis. We report the case of a nosocomial urethritis due to Corynebacterium striatum following resection of an intrameatus condyloma.

Mapping of genes for flower-related traits and QTLs for flowering ...

Indian Academy of Sciences (India)

Mapping of genes for flower-related traits and QTLs for flowering time in an interspecific population of Gossypium hirsutum × G. darwinii. Shuwen Zhang, Qianqian Lan, Xiang Gao, Biao Yang, Caiping Cai, Tianzhen Zhang and Baoliang Zhou. J. Genet. 95, 197–201. Table 1. Loci composition and recombination distances of ...

Neuroimaging Studies Of Striatum In Cognition, Part I: Healthy Individuals

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Jean-Sebastien eProvost

2015-10-01

Full Text Available The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.

Cocaine exposure shifts the balance of associative encoding from ventral to dorsolateral striatum

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Yuji Takahashi

2007-12-01

Full Text Available Both dorsal and ventral striatum are implicated in the "habitization" of behavior that occurs in addiction. Here we examined the effect of cocaine exposure on associative encoding in these two regions. Neural activity was recorded during go/no-go discrimination learning and reversal. Activity in ventral striatum developed and reversed rapidly, tracking the valence of the predicted outcome, whereas activity in dorsolateral striatum developed and reversed more slowly, tracking discriminative responding. This difference is consistent with the putative roles of these two areas in promoting habit-like behavior. Dorsolateral striatum has been directly implicated in habit or stimulus response learning, whereas ventral striatum appears to be involved indirectly by allowing cues associated with reward to exert a general motivational influence on responding. Interestingly cocaine exposure did not uniformly enhance processing across both regions. Instead cocaine reduced the degree and flexibility of cue-evoked firing in ventral striatum while marginally enhanced cue-selective firing in dorsolateral striatum. Thus cocaine exposure causes regionally specific effects on neural processing in striatum; these effects may promote the habitization of behavior by shifting control from ventral to dorsolateral regions.

Identification of novel QTLs for isolate-specific partial resistance to Plasmodiophora brassicae in Brassica rapa.

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Jingjing Chen

Full Text Available Plasmodiophora brassicae, the causal agent of clubroot disease of the Brassica crops, is widespread in the world. Quantitative trait loci (QTLs for partial resistance to 4 different isolates of P. brassicae (Pb2, Pb4, Pb7, and Pb10 were investigated using a BC1F1 population from a cross between two subspecies of Brassica rapa, i.e. Chinese cabbage inbred line C59-1 as a susceptible recurrent parent and turnip inbred line ECD04 as a resistant donor parent. The BC1F2 families were assessed for resistance under controlled conditions. A linkage map constructed with simple sequence repeats (SSR, unigene-derived microsatellite (UGMS markers, and specific markers linked to published clubroot resistance (CR genes of B. rapa was used to perform QTL mapping. A total of 6 QTLs residing in 5 CR QTL regions of the B. rapa chromosomes A01, A03, and A08 were identified to account for 12.2 to 35.2% of the phenotypic variance. Two QTL regions were found to be novel except for 3 QTLs in the respective regions of previously identified Crr1, Crr2, and Crr3. QTL mapping results indicated that 1 QTL region was common for partial resistance to the 2 isolates of Pb2 and Pb7, whereas the others were specific for each isolate. Additionally, synteny analysis between B. rapa and Arabidopsis thaliana revealed that all CR QTL regions were aligned to a single conserved crucifer blocks (U, F, and R on 3 Arabidopsis chromosomes where 2 CR QTLs were detected in A. thaliana. These results suggest that some common ancestral genomic regions were involved in the evolution of CR genes in B. rapa.

Meta-analysis of cotton fiber quality QTLs across diverse environments in a Gossypium hirsutum x G. barbadense RIL population.

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Lacape, Jean-Marc; Llewellyn, Danny; Jacobs, John; Arioli, Tony; Becker, David; Calhoun, Steve; Al-Ghazi, Yves; Liu, Shiming; Palaï, Oumarou; Georges, Sophie; Giband, Marc; de Assunção, Henrique; Barroso, Paulo Augusto Vianna; Claverie, Michel; Gawryziak, Gérard; Jean, Janine; Vialle, Michèle; Viot, Christopher

2010-06-28

Cotton fibers (produced by Gossypium species) are the premier natural fibers for textile production. The two tetraploid species, G. barbadense (Gb) and G. hirsutum (Gh), differ significantly in their fiber properties, the former having much longer, finer and stronger fibers that are highly prized. A better understanding of the genetics and underlying biological causes of these differences will aid further improvement of cotton quality through breeding and biotechnology. We evaluated an inter-specific Gh x Gb recombinant inbred line (RIL) population for fiber characteristics in 11 independent experiments under field and glasshouse conditions. Sites were located on 4 continents and 5 countries and some locations were analyzed over multiple years. The RIL population displayed a large variability for all major fiber traits. QTL analyses were performed on a per-site basis by composite interval mapping. Among the 651 putative QTLs (LOD > 2), 167 had a LOD exceeding permutation based thresholds. Coincidence in QTL location across data sets was assessed for the fiber trait categories strength, elongation, length, length uniformity, fineness/maturity, and color. A meta-analysis of more than a thousand putative QTLs was conducted with MetaQTL software to integrate QTL data from the RIL and 3 backcross populations (from the same parents) and to compare them with the literature. Although the global level of congruence across experiments and populations was generally moderate, the QTL clustering was possible for 30 trait x chromosome combinations (5 traits in 19 different chromosomes) where an effective co-localization of unidirectional (similar sign of additivity) QTLs from at least 5 different data sets was observed. Most consistent meta-clusters were identified for fiber color on chromosomes c6, c8 and c25, fineness on c15, and fiber length on c3. Meta-analysis provided a reliable means of integrating phenotypic and genetic mapping data across multiple populations and

Altered structural covariance of the striatum in functional dyspepsia patients.

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Liu, P; Zeng, F; Yang, F; Wang, J; Liu, X; Wang, Q; Zhou, G; Zhang, D; Zhu, M; Zhao, R; Wang, A; Gong, Q; Liang, F

2014-08-01

Functional dyspepsia (FD) is thought to be involved in dysregulation within the brain-gut axis. Recently, altered striatum activation has been reported in patients with FD. However, the gray matter (GM) volumes in the striatum and structural covariance patterns of this area are rarely explored. The purpose of this study was to examine the GM volumes and structural covariance patterns of the striatum between FD patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 FD patients and 39 HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes in the two groups. The caudate- or putamen-related regions identified from VBM analysis were then used as seeds to map the whole brain voxel-wise structural covariance patterns. Finally, a correlation analysis was used to investigate the effects of FD symptoms on the striatum. The results showed increased GM volumes in the bilateral putamen and right caudate. Compared with the structural covariance patterns of the HCs, the FD-related differences were mainly located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus, lingual gyrus, and cerebellum. And significant positive correlations were found between the volumes in the striatum and the FD duration in the patients. These findings provided preliminary evidence for GM changes in the striatum and different structural covariance patterns in patients with FD. The current results might expand our understanding of the pathophysiology of FD. © 2014 John Wiley & Sons Ltd.

Dopamine release in ventral striatum of pathological gamblers losing money

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Linnet, J; Peterson, E; Doudet, D J

2010-01-01

Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...

Reward-modulated motor information in identified striatum neurons.

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Isomura, Yoshikazu; Takekawa, Takashi; Harukuni, Rie; Handa, Takashi; Aizawa, Hidenori; Takada, Masahiko; Fukai, Tomoki

2013-06-19

It is widely accepted that dorsal striatum neurons participate in either the direct pathway (expressing dopamine D1 receptors) or the indirect pathway (expressing D2 receptors), controlling voluntary movements in an antagonistically balancing manner. The D1- and D2-expressing neurons are activated and inactivated, respectively, by dopamine released from substantia nigra neurons encoding reward expectation. However, little is known about the functional representation of motor information and its reward modulation in individual striatal neurons constituting the two pathways. In this study, we juxtacellularly recorded the spike activity of single neurons in the dorsolateral striatum of rats performing voluntary forelimb movement in a reward-predictable condition. Some of these neurons were identified morphologically by a combination of juxtacellular visualization and in situ hybridization for D1 mRNA. We found that the striatal neurons exhibited distinct functional activations before and during the forelimb movement, regardless of the expression of D1 mRNA. They were often positively, but rarely negatively, modulated by expecting a reward for the correct motor response. The positive reward modulation was independent of behavioral differences in motor performance. In contrast, regular-spiking and fast-spiking neurons in any layers of the motor cortex displayed only minor and unbiased reward modulation of their functional activation in relation to the execution of forelimb movement. Our results suggest that the direct and indirect pathway neurons cooperatively rather than antagonistically contribute to spatiotemporal control of voluntary movements, and that motor information is subcortically integrated with reward information through dopaminergic and other signals in the skeletomotor loop of the basal ganglia.

Identification of metabolic QTLs and candidate genes for glucosinolate synthesis in Brassica oleracea leaves, seeds and flower buds.

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Tamara Sotelo

Full Text Available Glucosinolates are major secondary metabolites found in the Brassicaceae family. These compounds play an essential role in plant defense against biotic and abiotic stresses, but more interestingly they have beneficial effects on human health. We performed a genetic analysis in order to identify the genome regions regulating glucosinolates biosynthesis in a DH mapping population of Brassica oleracea. In order to obtain a general overview of regulation in the whole plant, analyses were performed in the three major organs where glucosinolates are synthesized (leaves, seeds and flower buds. Eighty two significant QTLs were detected, which explained a broad range of variability in terms of individual and total glucosinolate (GSL content. A meta-analysis rendered eighteen consensus QTLs. Thirteen of them regulated more than one glucosinolate and its content. In spite of the considerable variability of glucosinolate content and profiles across the organ, some of these consensus QTLs were identified in more than one tissue. Consensus QTLs control the GSL content by interacting epistatically in complex networks. Based on in silico analysis within the B. oleracea genome along with synteny with Arabidopsis, we propose seven major candidate loci that regulate GSL biosynthesis in the Brassicaceae family. Three of these loci control the content of aliphatic GSL and four of them control the content of indolic glucosinolates. GSL-ALK plays a central role in determining aliphatic GSL variation directly and by interacting epistatically with other loci, thus suggesting its regulatory effect.

Spike-timing dependent plasticity in the striatum

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Elodie Fino

2010-06-01

Full Text Available The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs, are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, the NO synthase and cholinergic interneurons also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway.

Neuroimaging studies of the striatum in cognition Part I: healthy individuals.

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Provost, Jean-Sebastien; Hanganu, Alexandru; Monchi, Oury

2015-01-01

The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.

Shape abnormalities of the striatum in Alzheimer's disease.

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de Jong, Laura W; Ferrarini, Luca; van der Grond, Jeroen; Milles, Julien R; Reiber, Johan H C; Westendorp, Rudi G J; Bollen, Edward L E M; Middelkoop, Huub A M; van Buchem, Mark A

2011-01-01

Postmortem studies show pathological changes in the striatum in Alzheimer's disease (AD). Here, we examine the surface of the striatum in AD and assess whether changes of the surface are associated with impaired cognitive functioning. The shape of the striatum (n. accumbens, caudate nucleus, and putamen) was compared between 35 AD patients and 35 individuals without cognitive impairment. The striatum was automatically segmented from 3D T1 magnetic resonance images and automatic shape modeling tools (Growing Adaptive Meshes) were applied for morphometrical analysis. Repeated permutation tests were used to identify locations of consistent shape deformities of the striatal surface in AD. Linear regression models, corrected for age, gender, educational level, head size, and total brain parenchymal volume were used to assess the relation between cognitive performance and local surface deformities. In AD patients, differences of shape were observed on the medial head of the caudate nucleus and on the ventral lateral putamen, but not on the accumbens. The head of the caudate nucleus and ventral lateral putamen are characterized by extensive connections with the orbitofrontal and medial temporal cortices. Severity of cognitive impairment was associated with the degree of deformity of the surfaces of the accumbens, rostral medial caudate nucleus, and ventral lateral putamen. These findings provide evidence for the hypothesis that in AD primarily associative and limbic cerebral networks are affected.

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Pyramids of QTLs enhance host-plant resistance and Bt-mediated resistance to leaf-chewing insects in soybean.

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Ortega, María A; All, John N; Boerma, H Roger; Parrott, Wayne A

2016-04-01

QTL-M and QTL-E enhance soybean resistance to insects. Pyramiding these QTLs with cry1Ac increases protection against Bt-tolerant pests, presenting an opportunity to effectively deploy Bt with host-plant resistance genes. Plant resistance to leaf-chewing insects minimizes the need for insecticide applications, reducing crop production costs and pesticide concerns. In soybean [Glycine max (L.) Merr.], resistance to a broad range of leaf-chewing insects is found in PI 229358 and PI 227687. PI 229358's resistance is conferred by three quantitative trait loci (QTLs): M, G, and H. PI 227687's resistance is conferred by QTL-E. The letters indicate the soybean Linkage groups (LGs) on which the QTLs are located. This study aimed to determine if pyramiding PI 229358 and PI 227687 QTLs would enhance soybean resistance to leaf-chewing insects, and if pyramiding these QTLs with Bt (cry1Ac) enhances resistance against Bt-tolerant pests. The near-isogenic lines (NILs): Benning(ME), Benning(MGHE), and Benning(ME+cry1Ac) were developed. Benning(ME) and Benning(MGHE) were evaluated in detached-leaf and greenhouse assays with soybean looper [SBL, Chrysodeixis includens (Walker)], corn earworm [CEW, Helicoverpa zea (Boddie)], fall armyworm [FAW, Spodoptera frugiperda (J.E. Smith)], and velvetbean caterpillar [VBC, Anticarsia gemmatalis (Hübner)]; and in field-cage assays with SBL. Benning(ME+cry1Ac) was tested in detached-leaf assays against SBL, VBC, and Southern armyworm [SAW, Spodoptera eridania (Cramer)]. In the detached-leaf assay, Benning(ME) showed the strongest antibiosis against CEW, FAW, and VBC. In field-cage conditions, Benning(ME) and Benning(MGHE) suffered 61 % less defoliation than Benning. Benning(ME+cry1Ac) was more resistant than Benning(ME) and Benning (cry1Ac) against SBL and SAW. Agriculturally relevant levels of resistance in soybean can be achieved with just two loci, QTL-M and QTL-E. ME+cry1Ac could present an opportunity to protect the durability of Bt

Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

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Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko

2015-01-01

Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384

Genetic mapping of QTLs controlling fatty acids provided insights into the genetic control of fatty acid synthesis pathway in peanut (Arachis hypogaea L..

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Ming Li Wang

Full Text Available Peanut, a high-oil crop with about 50% oil content, is either crushed for oil or used as edible products. Fatty acid composition determines the oil quality which has high relevance to consumer health, flavor, and shelf life of commercial products. In addition to the major fatty acids, oleic acid (C18:1 and linoleic acid (C18:2 accounting for about 80% of peanut oil, the six other fatty acids namely palmitic acid (C16:0, stearic acid (C18:0, arachidic acid (C20:0, gadoleic acid (C20:1, behenic acid (C22:0, and lignoceric acid (C24:0 are accounted for the rest 20%. To determine the genetic basis and to improve further understanding on effect of FAD2 genes on these fatty acids, two recombinant inbred line (RIL populations namely S-population (high oleic line 'SunOleic 97R' × low oleic line 'NC94022' and T-population (normal oleic line 'Tifrunner' × low oleic line 'GT-C20' were developed. Genetic maps with 206 and 378 marker loci for the S- and the T-population, respectively were used for quantitative trait locus (QTL analysis. As a result, a total of 164 main-effect (M-QTLs and 27 epistatic (E-QTLs QTLs associated with the minor fatty acids were identified with 0.16% to 40.56% phenotypic variation explained (PVE. Thirty four major QTLs (>10% of PVE mapped on five linkage groups and 28 clusters containing more than three QTLs were also identified. These results suggest that the major QTLs with large additive effects would play an important role in controlling composition of these minor fatty acids in addition to the oleic and linoleic acids in peanut oil. The interrelationship among these fatty acids should be considered while breeding for improved peanut genotypes with good oil quality and desired fatty acid composition.

The role of dopamine in the nucleus accumbens and striatum during sexual behavior in the female rat.

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Becker, J B; Rudick, C N; Jenkins, W J

2001-05-01

Dopamine in dialysate from the nucleus accumbens (NAcc) increases during sexual and feeding behavior and after administration of drugs of abuse, even those that do not directly activate dopaminergic systems (e.g., morphine or nicotine). These findings and others have led to hypotheses that propose that dopamine is rewarding, predicts that reinforcement will occur, or attributes incentive salience. Examining increases in dopamine in NAcc or striatum during sexual behavior in female rats provides a unique situation to study these relations. This is because, for the female rat, sexual behavior is associated with an increase in NAcc dopamine and conditioned place preference only under certain testing conditions. This experiment was conducted to determine what factors are important for the increase in dopamine in dialysate from NAcc and striatum during sexual behavior in female rats. The factors considered were the number of contacts by the male, the timing of contacts by the male, or the ability of the female to control contacts by the male. The results indicate that increased NAcc dopamine is dependent on the timing of copulatory stimuli, independent of whether the female rat is actively engaged in regulating this timing. For the striatum, the timing of copulatory behavior influences the magnitude of the increase in dopamine in dialysate, but other factors are also involved. We conclude that increased extracellular dopamine in the NAcc and striatum conveys qualitative or interpretive information about the rewarding value of stimuli. Sexual behavior in the female rat is proposed as a model to determine the role of dopamine in motivated behavior.

Ventral and Dorsal Striatum Networks in Obesity: Link to Food Craving and Weight Gain.

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Contreras-Rodríguez, Oren; Martín-Pérez, Cristina; Vilar-López, Raquel; Verdejo-Garcia, Antonio

2017-05-01

The food addiction model proposes that obesity overlaps with addiction in terms of neurobiological alterations in the striatum and related clinical manifestations (i.e., craving and persistence of unhealthy habits). Therefore, we aimed to examine the functional connectivity of the striatum in excess-weight versus normal-weight subjects and to determine the extent of the association between striatum connectivity and individual differences in food craving and changes in body mass index (BMI). Forty-two excess-weight participants (BMI > 25) and 39 normal-weight participants enrolled in the study. Functional connectivity in the ventral and dorsal striatum was indicated by seed-based analyses on resting-state data. Food craving was indicated with subjective ratings of visual cues of high-calorie food. Changes in BMI between baseline and 12 weeks follow-up were assessed in 28 excess-weight participants. Measures of connectivity in the ventral striatum and dorsal striatum were compared between groups and correlated with craving and BMI change. Participants with excess weight displayed increased functional connectivity between the ventral striatum and the medial prefrontal and parietal cortices and between the dorsal striatum and the somatosensory cortex. Dorsal striatum connectivity correlated with food craving and predicted BMI gains. Obesity is linked to alterations in the functional connectivity of dorsal striatal networks relevant to food craving and weight gain. These neural alterations are associated with habit learning and thus compatible with the food addiction model of obesity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Isolate dependency of Brassica rapa resistance QTLs to Botrytis cinerea.

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Wei eZhang

2016-02-01

Full Text Available Generalist necrotrophic pathogens including Botrytis cinerea cause significant yield and financial losses on Brassica crops. However, there is little knowledge about the mechanisms underlying the complex interactions encoded by both host and pathogen genomes in this interaction. This potentially includes multiple layers of plant defense and pathogen virulence mechanisms that could complicate in breeding broad spectrum resistance within Brassica species. Glucosinolates are a diverse group of defense metabolites that play a key role in interaction between Brassica and biotic attackers. In this study, we utilized a collection of diverse B. cinerea isolates to investigate resistance within the B. rapa R500 x IMB211 recombinant inbred line population. We tested variation on lesion development and glucosinolate accumulation in parental lines and all population lines. We then mapped quantitative trait loci (QTL for both resistances to B. cinerea and defense metabolites in this population. Phenotypic analysis and QTL mapping demonstrate that the genetic basis of resistance to B. cinerea in B. rapa is isolate specific and polygenic with transgressive segregation that both parents contribute resistance alleles. QTLs controlling defensive glucosinolates are highly dependent on pathogen infection. An overlap of two QTLs identified between resistance to B. cinerea and defense metabolites also showed isolate specific effects. This work suggests that directly searching for resistance loci may not be the best approach at improving resistance in B. rapa to necrotrophic pathogen.

Attention modulates the dorsal striatum response to love stimuli.

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Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

2014-02-01

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

QTLs for seedling traits under salinity stress in hexaploid wheat

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Ren, Yongzhe; Xu, Yanhua; Teng, Wan; Li, Bin; Lin, Tongbao

2018-01-01

ABSTRACT: Soil salinity limits agricultural production and is a major obstacle for increasing crop yield. Common wheat is one of the most important crops with allohexaploid characteristic and a highly complex genome. QTL mapping is a useful way to identify genes for quantitative traits such as salinity tolerance in hexaploid wheat. In the present study, a hydroponic trial was carried out to identify quantitative trait loci (QTLs) associated with salinity tolerance of wheat under 150mM NaCl co...

Pulvinar projections to the striatum and amygdala

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Jonathan D Day-Brown

2010-11-01

Full Text Available Visually-guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as blindsight. Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri, a species considered to be a protypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd and central (Pc pulvinar both receive topographic (specific projections from SC, and Pd receives an additional nontopographic (diffuse projection from SC (Chomsung et al., 2008; JCN 510:24-46. Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP and parvalbumin (PV to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvinostriatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: 1 topographic visual information from SC to striatum to aid in guiding precise movements, and 2 nontopographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

Meta-analysis of cotton fiber quality QTLs across diverse environments in a Gossypium hirsutum x G. barbadense RIL population

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Giband Marc

2010-06-01

Full Text Available Abstract Background Cotton fibers (produced by Gossypium species are the premier natural fibers for textile production. The two tetraploid species, G. barbadense (Gb and G. hirsutum (Gh, differ significantly in their fiber properties, the former having much longer, finer and stronger fibers that are highly prized. A better understanding of the genetics and underlying biological causes of these differences will aid further improvement of cotton quality through breeding and biotechnology. We evaluated an inter-specific Gh × Gb recombinant inbred line (RIL population for fiber characteristics in 11 independent experiments under field and glasshouse conditions. Sites were located on 4 continents and 5 countries and some locations were analyzed over multiple years. Results The RIL population displayed a large variability for all major fiber traits. QTL analyses were performed on a per-site basis by composite interval mapping. Among the 651 putative QTLs (LOD > 2, 167 had a LOD exceeding permutation based thresholds. Coincidence in QTL location across data sets was assessed for the fiber trait categories strength, elongation, length, length uniformity, fineness/maturity, and color. A meta-analysis of more than a thousand putative QTLs was conducted with MetaQTL software to integrate QTL data from the RIL and 3 backcross populations (from the same parents and to compare them with the literature. Although the global level of congruence across experiments and populations was generally moderate, the QTL clustering was possible for 30 trait x chromosome combinations (5 traits in 19 different chromosomes where an effective co-localization of unidirectional (similar sign of additivity QTLs from at least 5 different data sets was observed. Most consistent meta-clusters were identified for fiber color on chromosomes c6, c8 and c25, fineness on c15, and fiber length on c3. Conclusions Meta-analysis provided a reliable means of integrating phenotypic and

Identification of putative QTLs for seedling stage phosphorus starvation response in finger millet (Eleusine coracana L. Gaertn. by association mapping and cross species synteny analysis.

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M Ramakrishnan

Full Text Available A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P responses by growing them in P sufficient (Psuf and P deficient (Pdef treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants. The low P tolerant genotypes were characterised by increased shoot and root length and increased root hair induction with longer root hairs under Pdef, than under Psuf. Association mapping of P response traits using mixed linear models revealed four quantitative trait loci (QTLs. Two QTLs (qLRDW.1 and qLRDW.2 for low P response affecting root dry weight explained over 10% phenotypic variation. In silico synteny analysis across grass genomes for these QTLs identified putative candidate genes such as Ser-Thr kinase and transcription factors such as WRKY and basic helix-loop-helix (bHLH. The QTLs for response under Psuf were mapped for traits such as shoot dry weight (qHSDW.1 and root length (qHRL.1. Putative associations of these QTLs over the syntenous regions on the grass genomes revealed proximity to cytochrome P450, phosphate transporter and pectin methylesterase inhibitor (PMEI genes. This is the first report of the extent of phenotypic variability for P response in finger millet genotypes during seedling-stage, along with the QTLs and putative candidate genes associated with P starvation tolerance.

Identification of putative QTLs for seedling stage phosphorus starvation response in finger millet (Eleusine coracana L. Gaertn.) by association mapping and cross species synteny analysis.

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Ramakrishnan, M; Ceasar, S Antony; Vinod, K K; Duraipandiyan, V; Ajeesh Krishna, T P; Upadhyaya, Hari D; Al-Dhabi, N A; Ignacimuthu, S

2017-01-01

A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P) responses by growing them in P sufficient (Psuf) and P deficient (Pdef) treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants. The low P tolerant genotypes were characterised by increased shoot and root length and increased root hair induction with longer root hairs under Pdef, than under Psuf. Association mapping of P response traits using mixed linear models revealed four quantitative trait loci (QTLs). Two QTLs (qLRDW.1 and qLRDW.2) for low P response affecting root dry weight explained over 10% phenotypic variation. In silico synteny analysis across grass genomes for these QTLs identified putative candidate genes such as Ser-Thr kinase and transcription factors such as WRKY and basic helix-loop-helix (bHLH). The QTLs for response under Psuf were mapped for traits such as shoot dry weight (qHSDW.1) and root length (qHRL.1). Putative associations of these QTLs over the syntenous regions on the grass genomes revealed proximity to cytochrome P450, phosphate transporter and pectin methylesterase inhibitor (PMEI) genes. This is the first report of the extent of phenotypic variability for P response in finger millet genotypes during seedling-stage, along with the QTLs and putative candidate genes associated with P starvation tolerance.

Bilaterally Asymmetric Effects of Quantitative Trait Loci (QTLs): QTLs That Affect Laxity in the Right Versus Left Coxofemoral (Hip) Joints of the Dog (Canis familiaris)

OpenAIRE

Chase, Kevin; Lawler, Dennis F.; Adler, Fred R.; Ostrander, Elaine A.; Lark, Karl G.

2004-01-01

In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint.A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxit...

Art for reward's sake: visual art recruits the ventral striatum.

Science.gov (United States)

Lacey, Simon; Hagtvedt, Henrik; Patrick, Vanessa M; Anderson, Amy; Stilla, Randall; Deshpande, Gopikrishna; Hu, Xiaoping; Sato, João R; Reddy, Srinivas; Sathian, K

2011-03-01

A recent study showed that people evaluate products more positively when they are physically associated with art images than similar non-art images. Neuroimaging studies of visual art have investigated artistic style and esthetic preference but not brain responses attributable specifically to the artistic status of images. Here we tested the hypothesis that the artistic status of images engages reward circuitry, using event-related functional magnetic resonance imaging (fMRI) during viewing of art and non-art images matched for content. Subjects made animacy judgments in response to each image. Relative to non-art images, art images activated, on both subject- and item-wise analyses, reward-related regions: the ventral striatum, hypothalamus and orbitofrontal cortex. Neither response times nor ratings of familiarity or esthetic preference for art images correlated significantly with activity that was selective for art images, suggesting that these variables were not responsible for the art-selective activations. Investigation of effective connectivity, using time-varying, wavelet-based, correlation-purged Granger causality analyses, further showed that the ventral striatum was driven by visual cortical regions when viewing art images but not non-art images, and was not driven by regions that correlated with esthetic preference for either art or non-art images. These findings are consistent with our hypothesis, leading us to propose that the appeal of visual art involves activation of reward circuitry based on artistic status alone and independently of its hedonic value. Copyright © 2010 Elsevier Inc. All rights reserved.

Identification of QTLs for resistance to powdery mildew and SSR markers diagnostic for powdery mildew resistance genes in melon (Cucumis melo L.).

Science.gov (United States)

Fukino, Nobuko; Ohara, Takayoshi; Monforte, Antonio J; Sugiyama, Mitsuhiro; Sakata, Yoshiteru; Kunihisa, Miyuki; Matsumoto, Satoru

2008-12-01

Powdery mildew caused by Podosphaera xanthii is an important foliar disease in melon. To find molecular markers for marker-assisted selection, we constructed a genetic linkage map of melon based on a population of 93 recombinant inbred lines derived from crosses between highly resistant AR 5 and susceptible 'Earl's Favourite (Harukei 3)'. The map spans 877 cM and consists of 167 markers, comprising 157 simple sequence repeats (SSRs), 7 sequence characterized amplified region/cleavage amplified polymorphic sequence markers and 3 phenotypic markers segregating into 20 linkage groups. Among them, 37 SSRs and 6 other markers were common to previous maps. Quantitative trait locus (QTL) analysis identified two loci for resistance to powdery mildew. The effects of these QTLs varied depending on strain and plant stage. The percentage of phenotypic variance explained for resistance to the pxA strain was similar between QTLs (R (2) = 22-28%). For resistance to pxB strain, the QTL on linkage group (LG) XII was responsible for much more of the variance (41-46%) than that on LG IIA (12-13%). The QTL on LG IIA was located between two SSR markers. Using an independent population, we demonstrated the effectiveness of these markers. This is the first report of universal and effective markers linked to a gene for powdery mildew resistance in melon.

Ionomics: Genes and QTLs controlling heavy metal uptake in perennial grasses grown on phytoxic soil

Science.gov (United States)

Perennial grasses occupy diverse soils throughout the world, including many sites contaminated with heavy metals. Uncovering the genetic architecture of QTLs controlling mineral homoeostasis is critical for understanding the biochemical pathways that determine the elemental profiles of perennial pl...

A sibling method for identifying vQTLs.

Science.gov (United States)

Conley, Dalton; Johnson, Rebecca; Domingue, Ben; Dawes, Christopher; Boardman, Jason; Siegal, Mark

2018-01-01

The propensity of a trait to vary within a population may have evolutionary, ecological, or clinical significance. In the present study we deploy sibling models to offer a novel and unbiased way to ascertain loci associated with the extent to which phenotypes vary (variance-controlling quantitative trait loci, or vQTLs). Previous methods for vQTL-mapping either exclude genetically related individuals or treat genetic relatedness among individuals as a complicating factor addressed by adjusting estimates for non-independence in phenotypes. The present method uses genetic relatedness as a tool to obtain unbiased estimates of variance effects rather than as a nuisance. The family-based approach, which utilizes random variation between siblings in minor allele counts at a locus, also allows controls for parental genotype, mean effects, and non-linear (dominance) effects that may spuriously appear to generate variation. Simulations show that the approach performs equally well as two existing methods (squared Z-score and DGLM) in controlling type I error rates when there is no unobserved confounding, and performs significantly better than these methods in the presence of small degrees of confounding. Using height and BMI as empirical applications, we investigate SNPs that alter within-family variation in height and BMI, as well as pathways that appear to be enriched. One significant SNP for BMI variability, in the MAST4 gene, replicated. Pathway analysis revealed one gene set, encoding members of several signaling pathways related to gap junction function, which appears significantly enriched for associations with within-family height variation in both datasets (while not enriched in analysis of mean levels). We recommend approximating laboratory random assignment of genotype using family data and more careful attention to the possible conflation of mean and variance effects.

A sibling method for identifying vQTLs

Science.gov (United States)

Domingue, Ben; Dawes, Christopher; Boardman, Jason; Siegal, Mark

2018-01-01

The propensity of a trait to vary within a population may have evolutionary, ecological, or clinical significance. In the present study we deploy sibling models to offer a novel and unbiased way to ascertain loci associated with the extent to which phenotypes vary (variance-controlling quantitative trait loci, or vQTLs). Previous methods for vQTL-mapping either exclude genetically related individuals or treat genetic relatedness among individuals as a complicating factor addressed by adjusting estimates for non-independence in phenotypes. The present method uses genetic relatedness as a tool to obtain unbiased estimates of variance effects rather than as a nuisance. The family-based approach, which utilizes random variation between siblings in minor allele counts at a locus, also allows controls for parental genotype, mean effects, and non-linear (dominance) effects that may spuriously appear to generate variation. Simulations show that the approach performs equally well as two existing methods (squared Z-score and DGLM) in controlling type I error rates when there is no unobserved confounding, and performs significantly better than these methods in the presence of small degrees of confounding. Using height and BMI as empirical applications, we investigate SNPs that alter within-family variation in height and BMI, as well as pathways that appear to be enriched. One significant SNP for BMI variability, in the MAST4 gene, replicated. Pathway analysis revealed one gene set, encoding members of several signaling pathways related to gap junction function, which appears significantly enriched for associations with within-family height variation in both datasets (while not enriched in analysis of mean levels). We recommend approximating laboratory random assignment of genotype using family data and more careful attention to the possible conflation of mean and variance effects. PMID:29617452

Molecular mapping of QTLs for resistance to Gibberella ear rot, in corn, caused by Fusarium graminearum.

Science.gov (United States)

Ali, M Liakat; Taylor, Jeff H; Jie, Liu; Sun, Genlou; William, Manilal; Kasha, Ken J; Reid, Lana M; Pauls, K Peter

2005-06-01

Gibberella ear rot, caused by the fungus Fusarium graminearum Schwabe, is a serious disease of corn (Zea mays) grown in northern climates. Infected corn is lower yielding and contains toxins that are dangerous to livestock and humans. Resistance to ear rot in corn is quantitative, specific to the mode of fungal entry (silk channels or kernel wounds), and highly influenced by the environment. Evaluations of ear rot resistance are complex and subjective; and they need to be repeated over several years. All of these factors have hampered attempts to develop F. graminearum resistant corn varieties. The aim of this study was to identify molecular markers linked to the genes for resistance to Gibberella ear rot. A recombinant inbred (RI) population, produced from a cross between a Gibberella ear rot resistant line (CO387) and a susceptible line (CG62), was field-inoculated and scored for Gibberella ear rot symptoms in the F4, F6, and F7 generations. The distributions of disease scores were continuous, indicating that resistance is probably conditioned by multiple loci. A molecular linkage map, based on segregation in the F5 RI population, contained 162 markers distributed over 10 linkage groups and had a total length of 2237 cM with an average distance between markers of 13.8 cM. Composite interval mapping identified 11 quantitative trait loci (QTLs) for Gibberella ear rot resistance following silk inoculation and 18 QTLs following kernel inoculation in 4 environments that accounted for 6.7%-35% of the total phenotypic variation. Only 2 QTLs (on linkage group 7) were detected in more than 1 test for silk resistance, and only 1 QTL (on linkage group 5) was detected in more than 1 test for kernel resistance, confirming the strong influence of the environment on these traits. The majority of the favorable alleles were derived from the resistant parent (CO387). The germplasm and markers for QTLs with significant phenotypic effects may be useful for marker-assisted selection

QTLs for straw quality characteristics identified in recombinant inbred lines of a Hordeum vulgare x H spontaneum cross in a Mediterranean environment

DEFF Research Database (Denmark)

Grando, S.; Baum, M.; Ceccarelli, S.

2005-01-01

Barley straw is commonly used as animal feed in many developing countries. Even a small increase in its nutritive value can have a large impact on animal production, and hence, on rural livelihood and human nutrition. Straw quality is strongly affected by environmental factors and is, therefore...... neutral detergent fiber, acid detergent fiber, lignin, digestible organic matter in dry matter, voluntary intake, crude protein, and straw morphology (the percentage of blades, sheaths, and stems). Localization of QTLs was performed using Windows QTL Cartographer, version 2.0. Seventy-three QTLs were...... identified, the majority of which (17) in the driest of the four environments. Only six QTLs were identified. ed in two environments; in five cases, one of the two was the wettest environment. This is discussed in relation to the possibility of improving straw quality in favorable environments where yields...

A statistical model for estimating maternal-zygotic interactions and parent-of-origin effects of QTLs for seed development.

Directory of Open Access Journals (Sweden)

Yanchun Li

Full Text Available Proper development of a seed requires coordinated exchanges of signals among the three components that develop side by side in the seed. One of these is the maternal integument that encloses the other two zygotic components, i.e., the diploid embryo and its nurturing annex, the triploid endosperm. Although the formation of the embryo and endosperm contains the contributions of both maternal and paternal parents, maternally and paternally derived alleles may be expressed differently, leading to a so-called parent-of-origin or imprinting effect. Currently, the nature of how genes from the maternal and zygotic genomes interact to affect seed development remains largely unknown. Here, we present a novel statistical model for estimating the main and interaction effects of quantitative trait loci (QTLs that are derived from different genomes and further testing the imprinting effects of these QTLs on seed development. The experimental design used is based on reciprocal backcrosses toward both parents, so that the inheritance of parent-specific alleles could be traced. The computing model and algorithm were implemented with the maximum likelihood approach. The new strategy presented was applied to study the mode of inheritance for QTLs that control endoreduplication traits in maize endosperm. Monte Carlo simulation studies were performed to investigate the statistical properties of the new model with the data simulated under different imprinting degrees. The false positive rate of imprinting QTL discovery by the model was examined by analyzing the simulated data that contain no imprinting QTL. The reciprocal design and a series of analytical and testing strategies proposed provide a standard procedure for genomic mapping of QTLs involved in the genetic control of complex seed development traits in flowering plants.

Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

NARCIS (Netherlands)

Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

Habit formation coincides with shifts in reinforcement representations in the sensorimotor striatum.

Science.gov (United States)

Smith, Kyle S; Graybiel, Ann M

2016-03-01

Evaluating outcomes of behavior is a central function of the striatum. In circuits engaging the dorsomedial striatum, sensitivity to goal value is accentuated during learning, whereas outcome sensitivity is thought to be minimal in the dorsolateral striatum and its habit-related corticostriatal circuits. However, a distinct population of projection neurons in the dorsolateral striatum exhibits selective sensitivity to rewards. Here, we evaluated the outcome-related signaling in such neurons as rats performed an instructional T-maze task for two rewards. As the rats formed maze-running habits and then changed behavior after reward devaluation, we detected outcome-related spike activity in 116 units out of 1,479 recorded units. During initial training, nearly equal numbers of these units fired preferentially either after rewarded runs or after unrewarded runs, and the majority were responsive at only one of two reward locations. With overtraining, as habits formed, firing in nonrewarded trials almost disappeared, and reward-specific firing declined. Thus error-related signaling was lost, and reward signaling became generalized. Following reward devaluation, in an extinction test, postgoal activity was nearly undetectable, despite accurate running. Strikingly, when rewards were then returned, postgoal activity reappeared and recapitulated the original early response pattern, with nearly equal numbers responding to rewarded and unrewarded runs and to single rewards. These findings demonstrate that outcome evaluation in the dorsolateral striatum is highly plastic and tracks stages of behavioral exploration and exploitation. These signals could be a new target for understanding compulsive behaviors that involve changes to dorsal striatum function. Copyright © 2016 the American Physiological Society.

BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

Science.gov (United States)

Costumero, Víctor; Barrós-Loscertales, Alfonso; Fuentes, Paola; Rosell-Negre, Patricia; Bustamante, Juan Carlos; Ávila, César

2016-09-01

According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

Human dorsal striatum encodes prediction errors during observational learning of instrumental actions.

Science.gov (United States)

Cooper, Jeffrey C; Dunne, Simon; Furey, Teresa; O'Doherty, John P

2012-01-01

The dorsal striatum plays a key role in the learning and expression of instrumental reward associations that are acquired through direct experience. However, not all learning about instrumental actions require direct experience. Instead, humans and other animals are also capable of acquiring instrumental actions by observing the experiences of others. In this study, we investigated the extent to which human dorsal striatum is involved in observational as well as experiential instrumental reward learning. Human participants were scanned with fMRI while they observed a confederate over a live video performing an instrumental conditioning task to obtain liquid juice rewards. Participants also performed a similar instrumental task for their own rewards. Using a computational model-based analysis, we found reward prediction errors in the dorsal striatum not only during the experiential learning condition but also during observational learning. These results suggest a key role for the dorsal striatum in learning instrumental associations, even when those associations are acquired purely by observing others.

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

Directory of Open Access Journals (Sweden)

Victoria L M Herrera

Full Text Available The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01 and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37 and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28, all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

Science.gov (United States)

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

Science.gov (United States)

Chung, Chia-Min; Wang, Ruey-Yun; Fann, Cathy S. J.; Chen, Jaw-Wen; Jong, Yuh-Shiun; Jou, Yuh-Shan; Yang, Hsin-Chou; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Pan, Wen-Harn

2013-01-01

Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10–16 to ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. PMID:23469169

Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

Directory of Open Access Journals (Sweden)

Silvana Vargas Superti

2009-04-01

Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

Hemiballism due to the lesion in the striatum demonstrated by CT scan

Energy Technology Data Exchange (ETDEWEB)

Kojima, S; Ito, N; Hirayama, K [Chiba Univ. (Japan). School of Medicine; Tochigi, S

1981-09-01

Two cases of hemiballism due to vascular lesions in the striatum demonstrated by CT scan were reported. Case 1 was a 58-year-old man with hypertension and diabetes mellitus, who had cerebral hemorrhage in the right striatum. Hemiballistic movements, which were confined to his face, neck and trunk as well as limbs of the left side, appeared soon after CVA and improved on treatment with haloperidol up to 4 mg per day. Case 2 was a 63-year-old woman with hypertension, who had probable cerebral infarct in the right striatum. The hemiballistic movements, confined to her right side, appeared soon after CVA and improved on treatment with chlorpromazine up to 50 mg per day, and perphenazine up to 6 mg per day. Whereas case 1 had contralateral hemiballism, case 2 had homolateral hemiballism, both due to vascular lesions in the striatum. Although it has been generally accepted, from postmortem and experimental studies, that the lesion responsible for hemiballism was localized in the contralateral subthalamic nucleus, a few cases of hemiballism have been reported, in which the subthalamic nucleus (Luys' body) and its connections appeared to be intact at necropsy. The present cases of hemiballism with involvement of the striatum without involvement of the subthalamic nucleus by CT scan, seem to be the first reported cases. It is not clear in the CT scan whether the subthalamic nucleus is also involved in addition to the striatal lesion, however, it is unlikely due to different vascular supplies to these areas. From a clinical and an experimental point of view, we would like to propose that hemiballism can occur due to the lesion in the striatum, especially the caudate nucleus even when the subthalamic nucleus and its connections are intact.

Identification of QTLs for seed germination capability after various storage periods using two RIL populations in rice.

Science.gov (United States)

Jiang, Wenzhu; Lee, Joohyun; Jin, Yong-Mei; Qiao, Yongli; Piao, Rihua; Jang, Sun Mi; Woo, Mi-Ok; Kwon, Soon-Wook; Liu, Xianhu; Pan, Hong-Yu; Du, Xinglin; Koh, Hee-Jong

2011-04-01

Seed germination capability of rice is one of the important traits in the production and storage of seeds. Quantitative trait loci (QTL) associated with seed germination capability in various storage periods was identified using two sets of recombinant inbred lines (RILs) which derived from crosses between Milyang 23 and Tong 88-7 (MT-RILs) and between Dasanbyeo and TR22183 (DT-RILs). A total of five and three main additive effects (QTLs) associated with seed germination capability were identified in MT-RILs and DT-RILs, respectively. Among them, six QTLs were identified repeatedly in various seed storage periods designated as qMT-SGC5.1, qMT-SGC7.2, and qMT-SGC9.1 on chromosomes 5, 7, and 9 in MT-RILs, and qDT-SGC2.1, qDT-SGC3.1, and qDT-SGC9.1 on chromosomes 2, 3, and 9 in DT-RILs, respectively. The QTL on chromosome 9 was identified in both RIL populations under all three storage periods, explaining up to 40% of the phenotypic variation. Eight and eighteen pairs additive × additive epistatic effect (epistatic QTL) were identified in MT-RILs and DT-RILs, respectively. In addition, several near isogenic lines (NILs) were developed to confirm six repeatable QTL effects using controlled deterioration test (CDT). The identified QTLs will be further studied to elucidate the mechanisms controlling seed germination capability, which have important implications for long-term seed storage.

Regulator of G protein signaling-12 modulates the dopamine transporter in ventral striatum and locomotor responses to psychostimulants.

Science.gov (United States)

Gross, Joshua D; Kaski, Shane W; Schroer, Adam B; Wix, Kimberley A; Siderovski, David P; Setola, Vincent

2018-02-01

Regulators of G protein signaling are proteins that accelerate the termination of effector stimulation after G protein-coupled receptor activation. Many regulators of G protein signaling proteins are highly expressed in the brain and therefore considered potential drug discovery targets for central nervous system pathologies; for example, here we show that RGS12 is highly expressed in microdissected mouse ventral striatum. Given a role for the ventral striatum in psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss significantly decreased hyperlocomotion to lower doses of both amphetamine and cocaine; however, other outcomes of administration (sensitization and conditioned place preference) were unaffected, suggesting that RGS12 does not function in support of the rewarding properties of these psychostimulants. To test whether observed response changes upon RGS12 loss were caused by changes to dopamine transporter expression and/or function, we prepared crude membranes from the brains of wild-type and RGS12-null mice and measured dopamine transporter-selective [ 3 H]WIN 35428 binding, revealing an increase in dopamine transporter levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address dopamine transporter function, we prepared striatal synaptosomes and measured [ 3 H]dopamine uptake. Consistent with increased [ 3 H]WIN 35428 binding, dopamine transporter-specific [ 3 H]dopamine uptake in RGS12-null ventral striatal synaptosomes was found to be increased. Decreased amphetamine-induced locomotor activity and increased [ 3 H]WIN 35428 binding were recapitulated with an independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates dopamine transporter expression and function in the ventral striatum, affecting amphetamine- and cocaine-induced increases in dopamine levels that specifically elicit acute hyperlocomotor responses.

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

Science.gov (United States)

Alloway, Kevin D.; Smith, Jared B.; Mowery, Todd M.; Watson, Glenn D. R.

2017-01-01

The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD) and related neurological disorders. PMID:28790899

Tracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L. Gaertn. Genotypes through Association Mapping and in silico Comparative Genomics Analyses.

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M Ramakrishnan

Full Text Available Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-β-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX for tiller production, calmodulin (CaM binding protein for seed yield and pectin methylesterase inhibitor (PMEI for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of

Tracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L.) Gaertn.) Genotypes through Association Mapping and in silico Comparative Genomics Analyses.

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Ramakrishnan, M; Antony Ceasar, S; Duraipandiyan, V; Vinod, K K; Kalpana, Krishnan; Al-Dhabi, N A; Ignacimuthu, S

2016-01-01

Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs) for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-β-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX) for tiller production, calmodulin (CaM) binding protein for seed yield and pectin methylesterase inhibitor (PMEI) for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of fungal

Ventral striatum activity when watching preferred pornographic pictures is correlated with symptoms of Internet pornography addiction.

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Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan

2016-04-01

One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

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Pamphyle Abedi Mukutenga

2012-08-01

Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

PROJECTIONS OF DORSAL AND MEDIAN RAPHE NUCLEI TO DORSAL AND VENTRAL STRIATUM

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G. R. Hassanzadeh G. Behzadi

2007-08-01

Full Text Available The ascending serotonergic projections are derived mainly from mesencephalic raphe nuclei. Topographical projections from mesencephalic raphe nuclei to the striatum were examined in the rat by the retrograde transport technique of HRP (horseradish peroxidase. In 29 rats stereotaxically injection of HRP enzyme were performed in dorsal and ventral parts of striatum separately. The extent of the injection sites and distribution of retrogradely labeled neuronal cell bodies were drawed on representative sections using a projection microscope. Following ipsilateral injection of HRP into the dorsal striatum, numerous labeled neurons were seen in rostral portion of dorsal raphe (DR nucleus. In the same level the cluster of labeled neurons were hevier through caudal parts of DR. A few neurons were also located in lateral wing of DR. More caudally some labeled neurons were found in lateral, medial line of DR. In median raphe nucleus (MnR the labeled neurons were scattered only in median portion of this nucleus. The ipsilateral injection of HRP into the ventral region of striatum resulted on labeling of numerous neurons in rostral, caudal and lateral portions of DR. Through the caudal extension of DR on 4th ventricle level, a large number of labeled neurons were distributed along the ventrocaudal parts of DR. In MnR, labeled neurons were observed only in median part of this nucleus. These findings suggest the mesencephalic raphe nuclei projections to caudo-putamen are topographically organized. In addition dorsal and median raphe nuclei have a stronger projection to the ventral striatum.

Mapping quantitative trait loci (QTLs for fatty acid composition in an interspecific cross of oil palm

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Sharma Mukesh

2009-08-01

Full Text Available Abstract Background Marker Assisted Selection (MAS is well suited to a perennial crop like oil palm, in which the economic products are not produced until several years after planting. The use of DNA markers for selection in such crops can greatly reduce the number of breeding cycles needed. With the use of DNA markers, informed decisions can be made at the nursery stage, regarding which individuals should be retained as breeding stock, which are satisfactory for agricultural production, and which should be culled. The trait associated with oil quality, measured in terms of its fatty acid composition, is an important agronomic trait that can eventually be tracked using molecular markers. This will speed up the production of new and improved oil palm planting materials. Results A map was constructed using AFLP, RFLP and SSR markers for an interspecific cross involving a Colombian Elaeis oleifera (UP1026 and a Nigerian E. guinneensis (T128. A framework map was generated for the male parent, T128, using Joinmap ver. 4.0. In the paternal (E. guineensis map, 252 markers (199 AFLP, 38 RFLP and 15 SSR could be ordered in 21 linkage groups (1815 cM. Interval mapping and multiple-QTL model (MQM mapping (also known as composite interval mapping, CIM were used to detect quantitative trait loci (QTLs controlling oil quality (measured in terms of iodine value and fatty acid composition. At a 5% genome-wide significance threshold level, QTLs associated with iodine value (IV, myristic acid (C14:0, palmitic acid (C16:0, palmitoleic acid (C16:1, stearic acid (C18:0, oleic acid (C18:1 and linoleic acid (C18:2 content were detected. One genomic region on Group 1 appears to be influencing IV, C14:0, C16:0, C18:0 and C18:1 content. Significant QTL for C14:0, C16:1, C18:0 and C18:1 content was detected around the same locus on Group 15, thus revealing another major locus influencing fatty acid composition in oil palm. Additional QTL for C18:0 was detected on Group 3

Identifying Quantitative Trait Loci (QTLs) and Developing Diagnostic Markers Linked to Orange Rust Resistance in Sugarcane (Saccharum spp.).

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Yang, Xiping; Islam, Md S; Sood, Sushma; Maya, Stephanie; Hanson, Erik A; Comstock, Jack; Wang, Jianping

2018-01-01

Sugarcane ( Saccharum spp.) is an important economic crop, contributing up to 80% of table sugar used in the world and has become a promising feedstock for biofuel production. Sugarcane production has been threatened by many diseases, and fungicide applications for disease control have been opted out for sustainable agriculture. Orange rust is one of the major diseases impacting sugarcane production worldwide. Identifying quantitative trait loci (QTLs) and developing diagnostic markers are valuable for breeding programs to expedite release of superior sugarcane cultivars for disease control. In this study, an F 1 segregating population derived from a cross between two hybrid sugarcane clones, CP95-1039 and CP88-1762, was evaluated for orange rust resistance in replicated trails. Three QTLs controlling orange rust resistance in sugarcane (qORR109, qORR4 and qORR102) were identified for the first time ever, which can explain 58, 12 and 8% of the phenotypic variation, separately. We also characterized 1,574 sugarcane putative resistance ( R ) genes. These sugarcane putative R genes and simple sequence repeats in the QTL intervals were further used to develop diagnostic markers for marker-assisted selection of orange rust resistance. A PCR-based Resistance gene-derived maker, G1 was developed, which showed significant association with orange rust resistance. The putative QTLs and marker developed in this study can be effectively utilized in sugarcane breeding programs to facilitate the selection process, thus contributing to the sustainable agriculture for orange rust disease control.

Localising QTLs for leaf rust resistance and agronomic traits in barley (¤Hordeum vulgare¤ L.)

DEFF Research Database (Denmark)

Kicherer, S.; Backes, G.; Walther, U.

2000-01-01

to leaf rust by means of artificial infection, heading date, plant height and Kernel weight were assessed. For leaf rust resistance, 4 QTLs were localised, that explained 96.1% of the genetic variation. One QTL on chromosome 4H confirmed a position found in another genetic background and one mapped...

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

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Kevin D. Alloway

2017-07-01

Full Text Available The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD and related neurological disorders.

Meta-analysis to refine map position and reduce confidence intervals for delayed canopy wilting QTLs in soybean

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Slow canopy wilting in soybean has been identified as a potentially beneficial trait for ameliorating drought effects on yield. Previous research identified QTLs for slow wilting from two different bi-parental populations and this information was combined with data from three other populations to id...

Aversive counterconditioning attenuates reward signalling in the ventral striatum

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Anne Marije Kaag

2016-08-01

Full Text Available Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient rewards such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional Magnetic Resonance Imaging (fMRI. In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signalling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signalling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

Reward prediction error signal enhanced by striatum-amygdala interaction explains the acceleration of probabilistic reward learning by emotion.

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Watanabe, Noriya; Sakagami, Masamichi; Haruno, Masahiko

2013-03-06

Learning does not only depend on rationality, because real-life learning cannot be isolated from emotion or social factors. Therefore, it is intriguing to determine how emotion changes learning, and to identify which neural substrates underlie this interaction. Here, we show that the task-independent presentation of an emotional face before a reward-predicting cue increases the speed of cue-reward association learning in human subjects compared with trials in which a neutral face is presented. This phenomenon was attributable to an increase in the learning rate, which regulates reward prediction errors. Parallel to these behavioral findings, functional magnetic resonance imaging demonstrated that presentation of an emotional face enhanced reward prediction error (RPE) signal in the ventral striatum. In addition, we also found a functional link between this enhanced RPE signal and increased activity in the amygdala following presentation of an emotional face. Thus, this study revealed an acceleration of cue-reward association learning by emotion, and underscored a role of striatum-amygdala interactions in the modulation of the reward prediction errors by emotion.

The involvement of the striatum in decision making

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Goulet-Kennedy, Julie; Labbe, Sara; Fecteau, Shirley

2016-01-01

Decision making has been extensively studied in the context of economics and from a group perspective, but still little is known on individual decision making. Here we discuss the different cognitive processes involved in decision making and its associated neural substrates. The putative conductors in decision making appear to be the prefrontal cortex and the striatum. Impaired decision-making skills in various clinical populations have been associated with activity in the prefrontal cortex and in the striatum. We highlight the importance of strengthening the degree of integration of both cognitive and neural substrates in order to further our understanding of decision-making skills. In terms of cognitive paradigms, there is a need to improve the ecological value of experimental tasks that assess decision making in various contexts and with rewards; this would help translate laboratory learnings into real-life benefits. In terms of neural substrates, the use of neuroimaging techniques helps characterize the neural networks associated with decision making; more recently, ways to modulate brain activity, such as in the prefrontal cortex and connected regions (eg, striatum), with noninvasive brain stimulation have also shed light on the neural and cognitive substrates of decision making. Together, these cognitive and neural approaches might be useful for patients with impaired decision-making skills. The drive behind this line of work is that decision-making abilities underlie important aspects of wellness, health, security, and financial and social choices in our daily lives. PMID:27069380

Neuronal basis for evaluating selected action in the primate striatum.

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Yamada, Hiroshi; Inokawa, Hitoshi; Matsumoto, Naoyuki; Ueda, Yasumasa; Kimura, Minoru

2011-08-01

Humans and animals optimize their behavior by evaluating outcomes of individual actions and predicting how much reward the actions will yield. While the estimated values of actions guide choice behavior, the choices are also governed by other behavioral norms, such as rules and strategies. Values, rules and strategies are represented in neuronal activity, and the striatum is one of the best qualified brain loci where these signals meet. To understand the role of the striatum in value- and strategy-based decision-making, we recorded striatal neurons in macaque monkeys performing a behavioral task in which they searched for a reward target by trial-and-error among three alternatives, earned a reward for a target choice, and then earned additional rewards for choosing the same target. This task allowed us to examine whether and how values of targets and strategy, which were defined as negative-then-search and positive-then-repeat (or win-stay-lose-switch), are represented in the striatum. Large subsets of striatal neurons encoded positive and negative outcome feedbacks of individual decisions and actions. Once monkeys made a choice, signals related to chosen actions, their values and search- or repeat-type actions increased and persisted until the outcome feedback appeared. Subsets of neurons exhibited a tonic increase in activity after the search- and repeat-choices following negative and positive feedback in the last trials as the task strategy monkeys adapted. These activity profiles as a heterogeneous representation of decision variables may underlie a part of the process for reinforcement- and strategy-based evaluation of selected actions in the striatum. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.

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Ippolita Cantuti-Castelvetri

2010-11-01

Full Text Available Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.Quantitative real-time polymerase chain reaction (PCR was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.

Inhibiting PKM[zeta] Reveals Dorsal Lateral and Dorsal Medial Striatum Store the Different Memories Needed to Support Adaptive Behavior

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Pauli, Wolfgang M.; Clark, Alexandra D.; Guenther, Heidi J.; O'Reilly, Randall C.; Rudy, Jerry W.

2012-01-01

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or…

Novel QTLs affecting rice kernel fissure resistance discovered in the cultivar ‘Saber’ augment those from ‘Cybonnet’

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Kernel fissures in rice (Oryza sativa L.) caused by pre- or post-harvest stresses are the leading cause of breakage among milled rice. Such breakage causes economic losses for producers, millers, and marketers. Five QTLs for kernel fissure resistance (FR) were identified among a set of 275 RILs de...

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

International Nuclear Information System (INIS)

Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

2002-01-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

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Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

2002-04-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

QTLs associated with agronomic traits in the Attila × CDC Go spring wheat population evaluated under conventional management.

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Jun Zou

Full Text Available Recently, we investigated the effect of the wheat 90K single nucleotide polymorphic (SNP array and three gene-specific (Ppd-D1, Vrn-A1 and Rht-B1 markers on quantitative trait loci (QTL detection in a recombinant inbred lines (RILs population derived from a cross between two spring wheat (Triticum aestivum L. cultivars, 'Attila' and 'CDC Go', and evaluated for eight agronomic traits at three environments under organic management. The objectives of the present study were to investigate the effect of conventional management on QTL detection in the same mapping population using the same set of markers as the organic management and compare the results with organic management. Here, we evaluated 167 RILs for number of tillers (tillering, flowering time, maturity, plant height, test weight (grain volume weight, 1000 kernel weight, grain yield, and grain protein content at seven conventionally managed environments from 2008 to 2014. Using inclusive composite interval mapping (ICIM on phenotypic data averaged across seven environments and a subset of 1203 informative markers (1200 SNPs and 3 gene specific markers, we identified a total of 14 QTLs associated with flowering time (1, maturity (2, plant height (1, grain yield (1, test weight (2, kernel weight (4, tillering (1 and grain protein content (2. Each QTL individually explained from 6.1 to 18.4% of the phenotypic variance. Overall, the QTLs associated with each trait explained from 9.7 to 35.4% of the phenotypic and from 22.1 to 90.8% of the genetic variance. Three chromosomal regions on chromosomes 2D (61-66 cM, 4B (80-82 cM and 5A (296-297 cM harbored clusters of QTLs associated with two to three traits. The coincidental region on chromosome 5A harbored QTL clusters for both flowering and maturity time, and mapped about 2 cM proximal to the Vrn-A1 gene, which was in high linkage disequilibrium (0.70 ≤ r2 ≤ 0.75 with SNP markers that mapped within the QTL confidence interval. Six of the 14

Differences between Dorsal and Ventral Striatum in the Sensitivity of Tonically Active Neurons to Rewarding Events

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Kevin Marche

2017-07-01

Full Text Available Within the striatum, cholinergic interneurons, electrophysiologically identified as tonically active neurons (TANs, represent a relatively homogeneous group in terms of their functional properties. They display typical pause in tonic firing in response to rewarding events which are of crucial importance for reinforcement learning. These responses are uniformly distributed throughout the dorsal striatum (i.e., motor and associative striatum, but it is unknown, at least in monkeys, whether differences in the modulation of TAN activity exist in the ventral striatum (i.e., limbic striatum, a region specialized for processing of motivational information. To address this issue, we examined the activity of dorsal and ventral TANs in two monkeys trained on a Pavlovian conditioning task in which a visual stimulus preceded the delivery of liquid reward by a fixed time interval. We found that the proportion of TANs responding to the stimulus predictive of reward did not vary significantly across regions (58%–80%, whereas the fraction of TANs responding to reward was higher in the limbic striatum (100% compared to the motor (65% and associative striatum (52%. By examining TAN modulation at the level of both the population and the individual neurons, we showed that the duration of pause responses to the stimulus and reward was longer in the ventral than in the dorsal striatal regions. Also, the magnitude of the pause was greater in ventral than dorsal striatum for the stimulus predictive of reward but not for the reward itself. We found similar region-specific differences in pause response duration to the stimulus when the timing of reward was less predictable (fixed replaced by variable time interval. Regional variations in the duration and magnitude of the pause response were transferred from the stimulus to reward when reward was delivered in the absence of any predictive stimulus. It therefore appears that ventral TANs exhibit stronger responses to

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

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Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

2016-08-01

Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

METHAMPHETAMINE-INDUCED CELL DEATH: SELECTIVE VULNERABILITY IN NEURONAL SUBPOPULATIONS OF THE STRIATUM IN MICE

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ZHU, J. P. Q.; XU, W.; ANGULO, J. A.

2010-01-01

Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an indirect dopamine agonist. In the striatum, METH has been shown to cause long lasting neurotoxic damage to dopaminergic nerve terminals and recently, the degeneration and death of striatal cells. The present study was undertaken to identify the type of striatal neurons that undergo apoptosis after METH. Male mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h later. To demonstrate that METH induces apoptosis in neurons, we combined terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining with immunohistofluorescence for the neuronal marker neuron-specific nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout the striatum. METH induces apoptosis in approximately 25% of striatal neurons. Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, dorsolateral and ventrolateral quadrants of the striatum did not reveal anatomical preference. The type of striatal neuron undergoing cell death was determined by combining TUNEL with immunohistofluorescence for selective markers of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45% of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of cholinergic neurons in the dorsal–medial striatum. In contrast, the SST-positive interneurons were refractory to METH-induced apoptosis. Finally, the amount of cell loss determined with Nissl staining correlated with the amount of TUNEL staining in the striatum of METH-treated animals. In conclusion, some of the striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH. This

Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET

International Nuclear Information System (INIS)

Iyo, Masaomi; Yamasaki, Toshiro; Fukuda, Hiroshi

1989-01-01

The effect of aging on 11 C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The ll normal volunteers (22 to 72 years old) participated in this study. The uptake of 11 C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11 C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant 'k 3 ' was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k 3 value with aging was observed. The k 3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum. (author)

Construction of 2 intraspecific linkage maps and identification of resistance QTLs for Phytophthora capsici root-rot and foliar-blight diseases of pepper (Capsicum annuum L.).

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Ogundiwin, Ebenezer A; Berke, Terry F; Massoudi, Mark; Black, Lowell L; Huestis, Gordon; Choi, Doil; Lee, Sanghyeob; Prince, James P

2005-08-01

Two linkage maps of pepper were constructed and used to identify quantitative trait loci (QTLs) conferring resistance to Phytophthora capsici. Inoculations were done with 7 isolates: 3 from Taiwan, 3 from California, and 1 from New Mexico. The first map was constructed from a set of recombinant inbred lines (RILs) of the PSP-11 (susceptible) x PI201234 (resistant) cross; and the second map was from a set of F(2) lines of the Joe E. Parker' (susceptible) x 'Criollo de Morelos 334' (resistant) cross. The RIL map covered 1466.1 cM of the pepper genome, and it consisted of 144 markers -- 91 amplified fragment length polymorphisms (AFLPs), 34 random amplified polymorphic DNA (RAPDs), 15 simple sequence repeats (SSRs), 1 sequence characterized amplified region (SCAR), and 3 morphological markers -- distributed over 17 linkage groups. The morphological markers mapped on this population were erect fruit habit (up), elongated fruit shape (fs(e)), and fasciculate fruit clusters (fa). The F(2) map consisted of 113 markers (51 AFLPs, 45 RAPDs, 14 SSRs, and 3 SCARs) distributed in 16 linkage groups, covering a total of 1089.2 cM of the pepper genome. Resistance to both root rot and foliar blight were evaluated in the RIL population using the 3 Taiwan isolates; the remaining isolates were used for the root-rot test only. Sixteen chromosomal regions of the RIL map contained single QTLs or clusters of resistance QTLs that had an effect on root rot and (or) foliar blight, revealing a complex set of genetics involved in resistance to P. capsici. Five QTLs were detected in the F(2) map that had an effect on resistance to root rot.

Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes Autistic-Like Behaviors.

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Lee, Yunjin; Kim, Hannah; Kim, Ji-Eun; Park, Jin-Young; Choi, Juli; Lee, Jung-Eun; Lee, Eun-Hwa; Han, Pyung-Lim

2018-07-01

The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

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Kim, Sang Eun; Shim, In Sop; Chung, June Key; Lee, Myung Chul

2002-01-01

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants

Effect of ginseng saponina on nicotine-induced dopamine release in the rat nucleus accumbens and striatum

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Eun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Shim, In Sop [Kyunghee University, Seoul (Korea, Republic of); Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2002-10-01

We investigated the effect of ginseng total saponin (GTS) on nicotine-induced dopamine (DA) release in the striatum and nucleus accumbens of freely moving rats using in vivo microdialysis technique. Systemic pretreatment with GTS decreased striatal DA release induced by local infusion of nicotine into the striatum. However, GTS had no effect on the resting levels of extracellular DA in the striatum. GTS also blocked nicotine-induced DA release in the nucleus accumbens. The results of the present study suggest that GTS acts on the DA terminals to prevent DA release induced by nicotine. This may reflect the blocking effect of GTS on behavioral hyperactivity induced by psychostimulants.

Mapping of QTLs for Seed Phorbol Esters, a Toxic Chemical in Jatropha curcas (L.).

Science.gov (United States)

Amkul, Kitiya; Laosatit, Kularb; Somta, Prakit; Shim, Sangrea; Lee, Suk-Ha; Tanya, Patcharin; Srinives, Peerasak

2017-08-18

Jatropha ( Jatropha curcas L.) is an oil-bearing plant that has potential to be cultivated as a biodiesel crop. The seed cake after oil extraction has 40-50% protein that can be used in animal feeds. A major limitation in utilizing the cake is the presence of phorbol esters (PE), a heat-tolerant toxic chemical. To identify the quantitative trait loci (QTLs) for PE, we constructed a genetic linkage map from an F₂ population of 95 individuals from a cross "Chai Nat" × "M10" using 143 simple sequence repeat (SSR) markers. M10 is low in seed PE while Chai Nat is high. Seeds from each F₂ individual were quantified for PE content by high performance liquid chromatography. A single marker analysis revealed five markers from linkage group 3 (LG3) and nine markers from LG8 associated with seed PE. Inclusive composite interval mapping identified two QTLs, each on LG3 ( qPE3.1 ) and LG8 ( qPE8.1 ) responsible for the PE. qPE3.1 and qPE8.1 accounted for 14.10%, and 15.49% of total variation in seed PE, respectively. Alelle(s) from M10 at qPE3.1 increased seed PE, while at qPE8.1 decreased seed PE. qPE3.1 is a new loci for PE, while qPE8.1 is the same locus with that reported recently for PE.

Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages.

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Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

2016-01-01

Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding.

Sunflower resistance to broomrape (Orobanche cumana is controlled by specific QTLs for different parasitism stages

Directory of Open Access Journals (Sweden)

Johann eLouarn

2016-05-01

Full Text Available Orobanche cumana (sunflower broomrape is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation.In our study, we used a population of 101 recombinant inbred lines (RILs, derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with H. debilis. Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i early attachment of the parasite to the sunflower roots, (ii young tubercle and (iii shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey and for the three stages of broomrape development.The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding.

Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages

Science.gov (United States)

Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

2016-01-01

Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding. PMID:27242810

Extensive training and hippocampus or striatum lesions: effect on place and response strategies.

Science.gov (United States)

Jacobson, Tara K; Gruenbaum, Benjamin F; Markus, Etan J

2012-02-01

The hippocampus has been linked to spatial navigation and the striatum to response learning. The current study focuses on how these brain regions continue to interact when an animal is very familiar with the task and the environment and must continuously switch between navigation strategies. Rats were trained to solve a plus maze using a place or a response strategy on different trials within a testing session. A room cue (illumination) was used to indicate which strategy should be used on a given trial. After extensive training, animals underwent dorsal hippocampus, dorsal lateral striatum or sham lesions. As expected hippocampal lesions predominantly caused impairment on place but not response trials. Striatal lesions increased errors on both place and response trials. Competition between systems was assessed by determining error type. Pre-lesion and sham animals primarily made errors to arms associated with the wrong (alternative) strategy, this was not found after lesions. The data suggest a qualitative change in the relationship between hippocampal and striatal systems as a task is well learned. During acquisition the two systems work in parallel, competing with each other. After task acquisition, the two systems become more integrated and interdependent. The fact that with extensive training (as something becomes a "habit"), behaviors become dependent upon the dorsal lateral striatum has been previously shown. The current findings indicate that dorsal lateral striatum involvement occurs even when the behavior is spatial and continues to require hippocampal processing. Published by Elsevier Inc.

Regional specialization within the human striatum for diverse psychological functions.

Science.gov (United States)

Pauli, Wolfgang M; O'Reilly, Randall C; Yarkoni, Tal; Wager, Tor D

2016-02-16

Decades of animal and human neuroimaging research have identified distinct, but overlapping, striatal zones, which are interconnected with separable corticostriatal circuits, and are crucial for the organization of functional systems. Despite continuous efforts to subdivide the human striatum based on anatomical and resting-state functional connectivity, characterizing the different psychological processes related to each zone remains a work in progress. Using an unbiased, data-driven approach, we analyzed large-scale coactivation data from 5,809 human imaging studies. We (i) identified five distinct striatal zones that exhibited discrete patterns of coactivation with cortical brain regions across distinct psychological processes and (ii) identified the different psychological processes associated with each zone. We found that the reported pattern of cortical activation reliably predicted which striatal zone was most strongly activated. Critically, activation in each functional zone could be associated with distinct psychological processes directly, rather than inferred indirectly from psychological functions attributed to associated cortices. Consistent with well-established findings, we found an association of the ventral striatum (VS) with reward processing. Confirming less well-established findings, the VS and adjacent anterior caudate were associated with evaluating the value of rewards and actions, respectively. Furthermore, our results confirmed a sometimes overlooked specialization of the posterior caudate nucleus for executive functions, often considered the exclusive domain of frontoparietal cortical circuits. Our findings provide a precise functional map of regional specialization within the human striatum, both in terms of the differential cortical regions and psychological functions associated with each striatal zone.

Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

Science.gov (United States)

Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

2011-05-01

Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Bipartite Community Structure of eQTLs.

Science.gov (United States)

Platig, John; Castaldi, Peter J; DeMeo, Dawn; Quackenbush, John

2016-09-01

Genome Wide Association Studies (GWAS) and expression quantitative trait locus (eQTL) analyses have identified genetic associations with a wide range of human phenotypes. However, many of these variants have weak effects and understanding their combined effect remains a challenge. One hypothesis is that multiple SNPs interact in complex networks to influence functional processes that ultimately lead to complex phenotypes, including disease states. Here we present CONDOR, a method that represents both cis- and trans-acting SNPs and the genes with which they are associated as a bipartite graph and then uses the modular structure of that graph to place SNPs into a functional context. In applying CONDOR to eQTLs in chronic obstructive pulmonary disease (COPD), we found the global network "hub" SNPs were devoid of disease associations through GWAS. However, the network was organized into 52 communities of SNPs and genes, many of which were enriched for genes in specific functional classes. We identified local hubs within each community ("core SNPs") and these were enriched for GWAS SNPs for COPD and many other diseases. These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions. These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits.

The role of the dorsoanterior striatum in implicit motivation: The case of the need for power

Directory of Open Access Journals (Sweden)

Oliver C Schultheiss

2013-04-01

Full Text Available Implicit motives like the need for power (nPower scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions in behavioral studies and (b activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2, 217-222 model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.

Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

Science.gov (United States)

Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

2011-01-01

Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum.

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Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan

2016-12-14

Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.

Control of Huntington’s Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2

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Lea J. Hachigian

2017-12-01

Full Text Available Summary: Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington’s disease (HD. The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT. Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes that present additional targets for normalization of corticostriatal dysfunction in HD. : Hachigian et al. demonstrate that manipulating levels of the striatum-enriched transcription factor Foxp2 can either rescue or mimic HD-associated behaviors in vivo. They link Foxp2 to the post-developmental regulation of the structure and function of the corticostriatal synapse. Keywords: Huntington’s disease, Foxp2, striatum, corticostriatal synapse

Coupling of MIC-3 overexpression with the chromosomes 11 and 14 root-knot nematode (RKN) (Meloidogyne incognita) resistance QTLs provides insights into the regulation of the RKN resistance response in Upland cotton (Gossypium hirsutum).

Science.gov (United States)

Wubben, Martin J; Callahan, Franklin E; Jenkins, Johnie N; Deng, Dewayne D

2016-09-01

Genetic analysis of MIC-3 transgene with RKN resistance QTLs provides insight into the resistance regulatory mechanism and provides a framework for testing additional hypotheses. Resistance to root-knot nematode (RKN) (Meloidogyne incognita) in Upland cotton (Gossypium hirsutum) is mediated by two major quantitative trait loci (QTL) located on chromosomes 11 and 14. The MIC-3 (Meloidogyne Induced Cotton3) protein accumulates specifically within the immature galls of RKN-resistant plants that possess these QTLs. Recently, we showed that MIC-3 overexpression in an RKN-susceptible cotton genotype suppressed RKN egg production but not RKN-induced root galling. In this study, the MIC-3 overexpression construct T-DNA in the single-copy transgenic line '14-7-1' was converted into a codominant molecular marker that allowed the marker assisted selection of F2:3 cotton lines, derived from a cross between 14-7-1 and M-240 RNR, having all possible combinations of the chromosomes 11 and 14 QTLs with and without the MIC-3 overexpression construct. Root-knot nematode reproduction (eggs g(-1) root) and severity of RKN-induced root galling were assessed in these lines. We discovered that the addition of MIC-3 overexpression suppressed RKN reproduction in lines lacking both resistance QTLs and in lines having only the chromosome 14 QTL, suggesting an additive effect of the MIC-3 construct with this QTL. In contrast, MIC-3 overexpression did not improve resistance in lines having the single chromosome 11 QTL or in lines having both resistance QTLs, suggesting an epistatic interaction between the chromosome 11 QTL and the MIC-3 construct. Overexpression of MIC-3 did not affect the severity of RKN-induced root galling regardless of QTL genotype. These data provide new insights into the relative order of action of the chromosomes 11 and 14 QTLs and their potential roles in regulating MIC-3 expression as part of the RKN resistance response.

A fundamental study on accumulation of [125I]IBZM in the rat striatum and on effect of non-labeled ligand

International Nuclear Information System (INIS)

Ishikawa, Nobuyoshi; Nakamura, Toshihiko; Satou, Motohiro; Takeda, Tohoru; Wu, Jin; Motoji, Naomi; Shigematsu, Akiyo.

1995-01-01

Iodo-125-labeled iodobenzamide ([ 125 I]IBZM) is used as a specific binding radioligand to dopamine D 2 receptors with high affinity and selectivity. The radioligand was homogeneously distributed in the whole brain initially after anministration, and rapidly washed out from the dopamine receptor-poor area followed by persistent retention in the striatum. Regression curve generated from striatum/cortex PSL ratio indicated the constant washout rate from striatum and cortex respectively. In the pretreated rat by cold benzamide (2 mg/kg), the accumulation of the radioligand was significantly suppressed in the striatum (48.8%). Iodine-125-labeled iodo-benzamide has the promise for investigation of dopamine D 2 receptors in the living brain. (author)

The construction of a Solanum habrochaites LYC4 introgression line population and the identification of QTLs for resistance to Botrytis cinerea

NARCIS (Netherlands)

Finkers, H.J.; Heusden, van A.W.; Meijer-Dekens, R.G.; Kan, van J.A.L.; Maris, P.C.; Lindhout, P.

2007-01-01

Tomato (Solanum lycopersicum) is susceptible to grey mold (Botrytis cinerea). Partial resistance to this fungus has been identified in accessions of wild relatives of tomato such as Solanum habrochaites LYC4. In a previous F-2 mapping study, three QTLs conferring resistance to B. cinerea (Rbcq1,

Dissection of QTLs for Hull Silicon Content on the Short Arm of Rice Chromosome 6

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Ji-rong WU

2010-06-01

Full Text Available The QTL qHUS6 for hull silicon content in rice was previously located on the short arm of rice chromosome 6. By using an F2:3 population segregating in the RM587–RM19784 region harboring qHUS6 in an isogenic background, two QTLs for hull silicon content were detected, of which qHUS6-1 was located in the distal region and qHUS6-2 in the region proximal to the centromere. Three rice plants carrying small heterozygous segments in the target region were selected, of which two covered the qHUS6-1 region and the other covered the qHUS6-2 region. Three F2:3 populations were derived from the selfed seeds of the three plants, respectively. QTL mapping was performed using the two populations segregating in the qHUS6-1 region, and qHUS6-1 was delimited to a 147.0-kb region flanked by the markers RM510 and RM19417. Five groups of F3 lines with different genotypic compositions in the qHUS6-2 region were selected from the other F2:3 population. Two QTLs were separated with two-way ANOVA, of which qHUS6-2a was located in the interval defined by RM19706–RM19795 and qHUS6-2b in the interval RM314–RM19665.

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

International Nuclear Information System (INIS)

Kienast, Thorsten; Rapp, Michael; Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias; Wrase, Jana; Heinz, Andreas; Braus, Dieter F.; Smolka, Michael N.; Mann, Karl; Roesch, Frank; Cumming, Paul; Gruender, Gerhard; Bartenstein, Peter

2008-01-01

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [ 18 F]DOPA for measurements of dopamine synthesis capacity and [ 18 F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [ 18 F]DOPA net influx constant K in app /[ 18 F]DMFP-binding potential (BP N D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Characterization of opaque2 modifier QTLs and candidate genes in recombinant inbred lines derived from the K0326Y quality protein maize inbred

KAUST Repository

Holding, David R.

2010-11-13

Quality protein maize (QPM) is a high lysine-containing corn that is based on genetic modification of the opaque2 (o2) mutant. In QPM, modifier genes convert the starchy endosperm of o2 to the vitreous phenotype of wild type maize. There are multiple, unlinked o2 modifier loci (Opm) in QPM and their nature and mode of action are unknown. We previously identified seven Opm QTLs and characterized 16 genes that are differentially up-regulated at a significant level in K0326Y QPM, compared to the starchy endosperm mutant W64Ao2. In order to further characterize these Opm QTLs and the genes up-regulated in K0326Y QPM, we created a population of 314 recombinant inbred lines (RILs) from a cross between K0326Y QPM and W64Ao2. The RILs were characterized for three traits associated with endosperm texture: vitreousness, density and hardness. Genetic linkage analysis of the RIL population confirmed three of the previously identified QTLs associated with o2 endosperm modification in K0326Y QPM. Many of the genes up-regulated in K0326Y QPM showed substantially higher levels of expression in vitreous compared with opaque RILs. These included genes associated with the upstream regulation of the ethylene response pathway, and a gene encoding a regulatory subunit of pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase, an adaptive enzyme of the glycolytic pathway. © 2010 Springer-Verlag.

The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum's Olfactory Tubercle

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Gadziola, Marie A.

2016-01-01

The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we

Amygdala and ventral striatum make distinct contributions to reinforcement learning

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Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

2016-01-01

Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

The influence of cannabinoids on learning and memory processes of the dorsal striatum.

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Goodman, Jarid; Packard, Mark G

2015-11-01

Extensive evidence indicates that the mammalian endocannabinoid system plays an integral role in learning and memory. Our understanding of how cannabinoids influence memory comes predominantly from studies examining cognitive and emotional memory systems mediated by the hippocampus and amygdala, respectively. However, recent evidence suggests that cannabinoids also affect habit or stimulus-response (S-R) memory mediated by the dorsal striatum. Studies implementing a variety of maze tasks in rats indicate that systemic or intra-dorsolateral striatum infusions of cannabinoid receptor agonists or antagonists impair habit memory. In mice, cannabinoid 1 (CB1) receptor knockdown can enhance or impair habit formation, whereas Δ(9)THC tolerance enhances habit formation. Studies in human cannabis users also suggest an enhancement of S-R/habit memory. A tentative conclusion based on the available data is that acute disruption of the endocannabinoid system with either agonists or antagonists impairs, whereas chronic cannabinoid exposure enhances, dorsal striatum-dependent S-R/habit memory. CB1 receptors are required for multiple forms of striatal synaptic plasticity implicated in memory, including short-term and long-term depression. Interactions with the hippocampus-dependent memory system may also have a role in some of the observed effects of cannabinoids on habit memory. The impairing effect often observed with acute cannabinoid administration argues for cannabinoid-based treatments for human psychopathologies associated with a dysfunctional habit memory system (e.g. post-traumatic stress disorder and drug addiction/relapse). In addition, the enhancing effect of repeated cannabinoid exposure on habit memory suggests a novel neurobehavioral mechanism for marijuana addiction involving the dorsal striatum-dependent memory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Vomeronasal inputs to the rodent ventral striatum.

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Ubeda-Bañon, I; Novejarque, A; Mohedano-Moriano, A; Pro-Sistiaga, P; Insausti, R; Martinez-Garcia, F; Lanuza, E; Martinez-Marcos, A

2008-03-18

Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.

Ratio of dopamine synthesis capacity to D2 receptor availability in ventral striatum correlates with central processing of affective stimuli

Energy Technology Data Exchange (ETDEWEB)

Kienast, Thorsten; Rapp, Michael [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Siessmeier, Thomas; Buchholz, Hans G.; Schreckenberger, Mathias [University of Mainz, Department of Nuclear Medicine, Mainz (Germany); Wrase, Jana; Heinz, Andreas [Charite Campus Mitte, Department of Psychiatry and Psychotherapy of the Charite University Medical Center, Berlin (Germany); Central Institute of Mental Health, Mannheim (Germany); Braus, Dieter F. [University of Hamburg, Neuroimage Nord, Department of Psychiatry, Hamburg (Germany); Smolka, Michael N.; Mann, Karl [Central Institute of Mental Health, Mannheim (Germany); Roesch, Frank [University of Mainz, Institute of Nuclear Chemistry, Mainz (Germany); Cumming, Paul [PET Center and Center for Functionally Integrative Neuroscience, Aarhus (Denmark); Gruender, Gerhard [Aachen University Medical Center, Department of Psychiatry of the RWTH, Mainz (Germany); Bartenstein, Peter [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

2008-06-15

Dopaminergic neurotransmission in the ventral striatum may interact with limbic processing of affective stimuli, whereas dorsal striatal dopaminergic neurotransmission can affect habitual processing of emotionally salient stimuli in the pre-frontal cortex. We investigated the dopaminergic neurotransmission in the ventral and dorsal striatum with respect to central processing of affective stimuli in healthy subjects. Subjects were investigated with positron emission tomography and [{sup 18}F]DOPA for measurements of dopamine synthesis capacity and [{sup 18}F]DMFP for estimation of dopamine D2 receptor binding potential. Functional magnetic resonance imaging was used to assess the blood-oxygen-level-dependent (BOLD) response to affective pictures, which was correlated with the ratio of [{sup 18}F]DOPA net influx constant K{sub in}{sup app} /[{sup 18}F]DMFP-binding potential (BP{sub N}D) in the ventral and dorsal striatum. The magnitude of the ratio in the ventral striatum was positively correlated with BOLD signal increases elicited by negative versus neutral pictures in the right medial frontal gyrus (BA10), right inferior parietal lobe and left post-central gyrus. In the dorsal striatum, the ratio was positively correlated with BOLD signal activation elicited by negative versus neutral stimuli in the left post-central gyrus. The BOLD signal elicited by positive versus neutral stimuli in the superior parietal gyrus was positively correlated with the dorsal and ventral striatal ratio. The correlations of the ratio in the ventral and dorsal striatum with processing of affective stimuli in the named cortical regions support the hypothesis that dopamine transmission in functional divisions of the striatum modulates processing of affective stimuli in specific cortical areas. (orig.)

Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation : A Genome-Wide Analysis among 1,800 South Asians

NARCIS (Netherlands)

Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes

Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model

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Yi Lu

2018-02-01

Full Text Available Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD, while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo1H nuclear magnetic resonance (NMR spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI and taurine (Tau were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

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Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

Existence and control of Go/No-Go decision transition threshold in the striatum.

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Jyotika Bahuguna

2015-04-01

Full Text Available A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Existence and control of Go/No-Go decision transition threshold in the striatum.

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Bahuguna, Jyotika; Aertsen, Ad; Kumar, Arvind

2015-04-01

A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.

Detection of QTLs for traits associated with pre-harvest sprouting resistance in bread wheat (Triticum aestivum L.).

Science.gov (United States)

Cao, Liangzi; Hayashi, Kazuki; Tokui, Mayumi; Mori, Masahiko; Miura, Hideho; Onishi, Kazumitsu

2016-03-01

Pre-harvest sprouting (PHS) is one of the serious problems for wheat production, especially in rainy regions. Although seed dormancy is the most critical trait for PHS resistance, the control of heading time should also be considered to prevent seed maturation during unfavorable conditions. In addition, awning is known to enhance water absorption by the spike, causing PHS. In this study, we conducted QTL analysis for three PHS resistant related traits, seed dormancy, heading time and awn length, by using recombinant inbred lines from 'Zenkouji-komugi' (high PHS resistance) × 'Chinese Spring' (weak PHS resistance). QTLs for seed dormancy were detected on chromosomes 1B (QDor-1B) and 4A (QDor-4A), in addition to a QTL on chromosome 3A, which was recently cloned as TaMFT-3A. In addition, the accumulation of the QTLs and their epistatic interactions contributed significantly to a higher level of dormancy. QDor-4A is co-located with the Hooded locus for awn development. Furthermore, an effective QTL, which confers early heading by the Zenkouji-komugi allele, was detected on the short arm of chromosome 7B, where the Vrn-B3 locus is located. Understanding the genetic architecture of traits associated with PHS resistance will facilitate the marker assisted selection to breed new varieties with higher PHS resistance.

Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

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Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

2015-12-01

Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

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Julie eBoulanger Bertolus

2014-05-01

Full Text Available Interval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days post-natal during odor-fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed.

Antioxidant responses and photosynthetic behaviors of Kappaphycus alvarezii and Kappaphycus striatum (Rhodophyta, Solieriaceae) during low temperature stress.

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Li, Hu; Liu, Jianguo; Zhang, Litao; Pang, Tong

2016-12-01

Kappaphycus are farmed in tropical countries as raw material for carrageenan, which is widely used in food industry. The sea area available for farming is one limiting factor in the production of seaweeds. Though cultivation is spreading into subtropical regions, the lower seawater temperature is an important problem encountered in subtropical regions for the farming of Kappaphycus. This research of physiological response to low temperature stress will be helpful for screening Kappaphycus strains for growth in a lower temperature environment. Responses of antioxidant systems and photosystem II (PSII) behaviors in Kappaphycus alvarezii and Kappaphycus striatum were evaluated during low temperature treatments (23, 20, 17 °C). Compared with the controls at 26 °C, the H 2 O 2 concentrations increased in both species when the thalli were exposed to low temperatures (23, 20, 17 °C), but these increases were much greater in K. striatum than in K. alvarezii thalli, suggesting that K. striatum suffered more oxidative stress. The activities of some important antioxidant enzymes (e.g. superoxide dismutase and ascorbate peroxidase) and the hydroxyl free radical scavenging capacity were substantially higher at 23, 20 and 17 °C than at the control 26 °C in K. alvarezii, indicating that the antioxidant system of K. alvarezii enhanced its resistance to low temperature. However, no significant increases of antioxidant enzymes activities were observed at 20 and 17 °C in K. striatum. In addition, both the maximal efficiency of PSII photochemistry (F V /F m ) and the performance index (PI ABS ) decreased significantly in K. striatum at 23 °C, indicating that the photosynthetic apparatus was damaged at 23 °C. In contrast, no significant decreases of either F V /F m or PI ABS were observed in K. alvarezii at 23 °C. It is concluded that K. alvarezii has greater tolerance to low temperature than K. striatum.

Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum

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Haiyan Jiang

2018-05-01

Full Text Available The caudal region of the rodent striatum, called the tail of the striatum (TS, is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

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Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

2010-08-01

Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

A common currency for the computation of motivational values in the human striatum

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Li, Yansong; Dreher, Jean-Claude

2015-01-01

Reward comparison in the brain is thought to be achieved through the use of a ‘common currency’, implying that reward value representations are computed on a unique scale in the same brain regions regardless of the reward type. Although such a mechanism has been identified in the ventro-medial prefrontal cortex and ventral striatum in the context of decision-making, it is less clear whether it similarly applies to non-choice situations. To answer this question, we scanned 38 participants with fMRI while they were presented with single cues predicting either monetary or erotic rewards, without the need to make a decision. The ventral striatum was the main brain structure to respond to both cues while showing increasing activity with increasing expected reward intensity. Most importantly, the relative response of the striatum to monetary vs erotic cues was correlated with the relative motivational value of these rewards as inferred from reaction times. Similar correlations were observed in a fronto-parietal network known to be involved in attentional focus and motor readiness. Together, our results suggest that striatal reward value signals not only obey to a common currency mechanism in the absence of choice but may also serve as an input to adjust motivated behaviour accordingly. PMID:24837478

High Density Linkage Map Construction and Mapping of Yield Trait QTLs in Maize (Zea mays) Using the Genotyping-by-Sequencing (GBS) Technology

Science.gov (United States)

Su, Chengfu; Wang, Wei; Gong, Shunliang; Zuo, Jinghui; Li, Shujiang; Xu, Shizhong

2017-01-01

Increasing grain yield is the ultimate goal for maize breeding. High resolution quantitative trait loci (QTL) mapping can help us understand the molecular basis of phenotypic variation of yield and thus facilitate marker assisted breeding. The aim of this study is to use genotyping-by-sequencing (GBS) for large-scale SNP discovery and simultaneous genotyping of all F2 individuals from a cross between two varieties of maize that are in clear contrast in yield and related traits. A set of 199 F2 progeny derived from the cross of varieties SG-5 and SG-7 were generated and genotyped by GBS. A total of 1,046,524,604 reads with an average of 5,258,918 reads per F2 individual were generated. This number of reads represents an approximately 0.36-fold coverage of the maize reference genome Zea_mays.AGPv3.29 for each F2 individual. A total of 68,882 raw SNPs were discovered in the F2 population, which, after stringent filtering, led to a total of 29,927 high quality SNPs. Comparative analysis using these physically mapped marker loci revealed a higher degree of synteny with the reference genome. The SNP genotype data were utilized to construct an intra-specific genetic linkage map of maize consisting of 3,305 bins on 10 linkage groups spanning 2,236.66 cM at an average distance of 0.68 cM between consecutive markers. From this map, we identified 28 QTLs associated with yield traits (100-kernel weight, ear length, ear diameter, cob diameter, kernel row number, corn grains per row, ear weight, and grain weight per plant) using the composite interval mapping (CIM) method and 29 QTLs using the least absolute shrinkage selection operator (LASSO) method. QTLs identified by the CIM method account for 6.4% to 19.7% of the phenotypic variation. Small intervals of three QTLs (qCGR-1, qKW-2, and qGWP-4) contain several genes, including one gene (GRMZM2G139872) encoding the F-box protein, three genes (GRMZM2G180811, GRMZM5G828139, and GRMZM5G873194) encoding the WD40-repeat protein, and

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

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Mathew Jobin

2009-04-01

Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

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Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

2013-01-01

In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

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Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

[Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora].

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Liu, Ping; He, Xinrong; Guo, Mei

2010-04-01

To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P Calculus Bovis group was higher than combination group (P Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy.

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

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Mattfeld, Aaron T.; Stark, Craig E. L.

2015-01-01

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

Isolation and characterization of neural stem cells from human fetal striatum

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Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

2005-01-01

This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

Manganese-Disrupted Interaction of Dopamine D1 and NMDAR in the Striatum to Injury Learning and Memory Ability of Mice.

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Song, Qifan; Deng, Yu; Yang, Xinxin; Bai, Ying; Xu, Bin; Liu, Wei; Zheng, Wenxue; Wang, Can; Zhang, Meng; Xu, Zhaofa

2016-12-01

Manganese (Mn) is widely regarded as a neurotoxic heavy metal that causes learning and memory deficits. Recently, it has been proved that the striatum is related to memory and learning ability. However, no previous study focused on the effect of Mn-induced learning and memory deficits on the striatum. This study aims to investigate the probable interaction of dopamine D1 receptor (DR1) and N-methyl-D-aspartate receptor (NMDAR), two cognition-related receptors in the striatum during Mn exposure. Mice are randomly divided into four groups, including control group, 12.5 mg/kg MnCl 2 group, 25 mg/kg MnCl 2 group, and 50 mg/kg MnCl 2 group. The mice receive intraperitoneal injections of 0, 12.5, 25, and 50 mg/kg MnCl 2 once daily for 2 weeks. Then, learning and memory ability, pathological changes, expression, and interaction of DR1 and NMDAR are determined. It has been found that Mn disrupted spatial learning and memory ability of mice by Morris water maze test and the passive avoidance test. Pathological and ultrastructure were injured. Mn decreased the immunohistochemical activities, protein levels, and messenger RNA (mRNA) expression of DR1, NR1, and NR2A. Mn exposure inhibited interaction between DR1 and NMDAR in striatum by double immunofluorescent staining and co-immunoprecipitation. In conclusion, our study illustrated that Mn caused learning and memory dysfunction via injury of striatum and inhibition of interaction between DR1 and NMDAR in striatum.

Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

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Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

2009-02-11

Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

The role of the striatum in effort-based decision-making in the absence of reward.

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Schouppe, Nathalie; Demanet, Jelle; Boehler, Carsten N; Ridderinkhof, K Richard; Notebaert, Wim

2014-02-05

Decision-making involves weighing costs against benefits, for instance, in terms of the effort it takes to obtain a reward of a given magnitude. This evaluation process has been linked to the dorsal anterior cingulate cortex (dACC) and the striatum, with activation in these brain structures reflecting the discounting effect of effort on reward. Here, we investigate how cognitive effort influences neural choice processes in the absence of an extrinsic reward. Using functional magnetic resonance imaging in humans, we used an effort-based decision-making task in which participants were required to choose between two options for a subsequent flanker task that differed in the amount of cognitive effort. Cognitive effort was manipulated by varying the proportion of incongruent trials associated with each choice option. Choice-locked activation in the striatum was higher when participants chose voluntarily for the more effortful alternative but displayed the opposite trend on forced-choice trials. The dACC revealed a similar, yet only trend-level significant, activation pattern. Our results imply that activation levels in the striatum reflect a cost-benefit analysis, in which a balance is made between effort discounting and the intrinsic motivation to choose a cognitively challenging task. Moreover, our findings indicate that it matters whether this challenge is voluntarily chosen or externally imposed. As such, the present findings contrast with classical findings on effort discounting that found reductions in striatum activation for higher effort by finding enhancements of the same neural circuits when a cognitively challenging task is voluntarily selected and does not entail the danger of losing reward.

In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

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Heimfarth, Luana; Loureiro, Samanta Oliveira; Dutra, Márcio Ferreira; Andrade, Cláudia; Pettenuzzo, Letícia; Guma, Fátima T. Costa Rodrigues; Gonçalves, Carlos Alberto Saraiva [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil); Batista Teixeira da Rocha, João [Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS Brazil (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS (Brazil)

2012-10-15

In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe){sub 2}/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe){sub 2} significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe){sub 2} provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe){sub 2} treated striatal slices suggested apoptotic cell death. (PhTe){sub 2} exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe){sub 2}-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. -- Highlights: ► Diphenyl ditelluride causes apoptotic neuronal death in the striatum of young rats. ► Diphenyl ditelluride causes reactive astrogliosis in the striatum of rats. ► Diphenyl ditelluride disrupts the homeostasis of the cytoskeleton of the striatum. ► The actions of diphenyl ditelluride are mediated by MAPK and Akt

Gene expression in rat striatum following carbon monoxide poisoning

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Shuichi Hara

2017-06-01

Full Text Available Carbon monoxide (CO poisoning causes brain damage, which is attenuated by treatment with hydrogen [1,2], a scavenger selective to hydroxyl radical (·≡OH [3]. This suggests a role of ·≡OH in brain damage due to CO poisoning. Studies have shown strong enhancement of ·≡OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb level >70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with ·≡OH production [5] might contribute to ·≡OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO database under accession number GSE94780.

Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior

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van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.

2014-01-01

Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and

The Role of the Neuropeptide Somatostatin on Methamphetamine and Glutamate-Induced Neurotoxicity in the Striatum of Mice

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Afanador, Lauriaselle; Mexhitaj, Ina; Diaz, Carolyn; Ordonez, Dalila; Baker, Lisa; Angulo, Jesus A.

2014-01-01

A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30 mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms. PMID:23524190

Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

International Nuclear Information System (INIS)

Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2004-01-01

Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2→3.9%, CA: 57.4→14.1%, ST: 17.7→0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction

Effects of head motion correction on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

2004-07-01

Neuroreceptor PET studies require 60-90 minutes to complete. Head motion of the subject increases the uncertainty in measured activity. In this study, the effects of the data-driven head motion correction on the evaluation of endogenous dopamine (DA) release in the striatum were investigated. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a monetary reward for 40 min. Dynamic frames acquired during the equilibrium condition (rest: 30-50 min, game: 70-90 min) were realigned to the first frame at resting condition. Intra-condition registration between the frames during both the rest and game condition were performed, and average image for each condition was created and registered with each other again (inter-condition registration). Resting PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the other one. Volumes of interest (VOl) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DA release was calculated as the percent change of BP after the video game. Changes in position and orientation of the striatum during the PET scan were observed before the head motion correction. BP values at resting condition were not changed significantly after the intra-condition registration. However, the BP values during the video game and DA release (PU: 29.2{yields}3.9%, CA: 57.4{yields}14.1%, ST: 17.7{yields}0.6%) were significantly changed after the correction. The results suggest that overestimation of the DA release caused by the head motion during PET scan and misalignment of MRI-based VOl and the striatum in PET image was remedied by the data-driven head motion correction.

Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

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Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

2016-02-01

We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

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Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

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Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita; Pope, Carey

2006-01-01

This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted in any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat.

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Brodnik, Zachary D; Double, Manda; España, Rodrigo A; Jaskiw, George E

2017-09-01

We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250-1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500-1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125-250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5-50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and/or disordered L-TYR transport have been implicated. Published by Elsevier Ltd.

Dopamine dynamics and cocaine sensitivity differ between striosome and matrix compartments of the striatum

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Salinas, Armando G.; Davis, Margaret I.; Lovinger, David M.; Mateo, Yolanda

2016-01-01

The striatum is typically classified according to its major output pathways, which consist of dopamine D1 and D2 receptor-expressing neurons. The striatum is also divided into striosome and matrix compartments, based on the differential expression of a number of proteins, including the mu opioid receptor, dopamine transporter (DAT), and Nr4a1 (nuclear receptor subfamily 4, group A, member 1). Numerous functional differences between the striosome and matrix compartments are implicated in dopamine-related neurological disorders including Parkinson’s disease and addiction. Using Nr4a1-eGFP mice, we provide evidence that electrically evoked dopamine release differs between the striosome and matrix compartments in a regionally-distinct manner. We further demonstrate that this difference is not due to differences in inhibition of dopamine release by dopamine autoreceptors or nicotinic acetylcholine receptors. Furthermore, cocaine enhanced extracellular dopamine in striosomes to a greater degree than in the matrix and concomitantly inhibited dopamine uptake in the matrix to a greater degree than in striosomes. Importantly, these compartment differences in cocaine sensitivity were limited to the dorsal striatum. These findings demonstrate a level of exquisite microanatomical regulation of dopamine by the DAT in striosomes relative to the matrix. PMID:27036891

Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

Science.gov (United States)

Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

2009-01-01

Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

Amphetamine-enhanced accumulation of [3H]-spiperone in mouse corpus striatum in vivo: Modification by other drugs

International Nuclear Information System (INIS)

Dorris, R.L.

1989-01-01

Other investigators have reported that amphetamine administered to rodents results in an increase in the in vivo accumulation of either the tritiated dopamine receptor ligand, spiperone or pimozide in the dopaminergic corpus striatum, (specific binding) while not altering that in the sparsely dopaminergically innervated cerebellum (non-specific binding). Experiments were undertaken to determine if the results could be replicated and if some other drugs would modify the effect. Male mice were injected with [ 3 H]-spiperone (20 μCi/Kg, 0.0003 mg/kg) s.c. and killed 2 hrs later for determination of radioactivity in corpus striatum and cerebellum. Amphetamine (20 mg/kg, i.p.) given 15 min before [ 3 H]-spiperone, increased accumulation in striatum but not cerebellum. The increase was inhibited by α - methyltyrosine (α-MT), haloperidol, reserpine or amantadine. It is suggested that the amphetamine-induced increase in accumulation of [ 3 H]-spiperone in corpus striatum (specific binding) depends on release of large amounts of dopamine, which then must be able to interact with the dopamine receptor. The antagonism of the effect by α-MT or reserpine can be explained by dopamine depletion, that of haloperidol by antagonism for binding at the receptor site. It is suggested that amantadine acts by a dual mechanism: (1) as a low efficacy agonist, it competes for binding to the receptor and (2) it has some ability to block dopamine release

Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

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Hiroaki Kawamichi

2016-11-01

Full Text Available Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that romantic relationship is associated with structural differences in the striatum related to the positive subjective experience of being in a romantic relationship. Because intimate romantic relationships contribute to perceived subjective happiness, this subjective enhancement of happiness might be accompanied by the experience of positive events related to being in a romantic relationship. To test this hypothesis and elucidate the structure involved, we compared subjective happiness, an indirect measure of the existence of positive experiences caused by being in a romantic relationship, of participants with or without romantic partners (N = 68. Furthermore, we also conducted a voxel-based morphometry (VBM study of the effects of being in a romantic relationship (N = 113. Being in a romantic relationship was associated with greater subjective happiness and reduced gray matter density within the right dorsal striatum. These results suggest that being in a romantic relationship enhances perceived subjective happiness via positive experiences. Furthermore, the observed reduction in gray matter density in the right dorsal striatum may reflect an increase in saliency of social reward within a romantic relationship. Thus, being in a romantic relationship is associated with positive experiences and a reduction of gray matter density in the right dorsal striatum, representing a modulation of social reward.

More consistently altered connectivity patterns for cerebellum and medial temporal lobes than for amygdala and striatum in schizophrenia

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Henning ePeters

2016-02-01

Full Text Available Background: Brain architecture can be divided into a cortico-thalamic system and modulatory ‘subcortical-cerebellar’ systems containing key structures such as striatum, medial temporal lobes (MTLs, amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems’ connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems’ connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI. Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems’ activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs (i.e., striatum, MTL, amygdala, cerebellum. Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices (i.e. connectivity between NW and ROIs (allROIs-NW, separateROI-NW, only NWs (NWs-NWs, and only ROIs (allROIs-allROIs as main outcome measures, which were classified by support-vector-machine-based leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56% and 74%, respectively. Considering separate

Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

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Makoto Ito

2015-11-01

Full Text Available Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS, the dorsomedial striatum (DMS, and the ventral striatum (VS identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

Parallel Representation of Value-Based and Finite State-Based Strategies in the Ventral and Dorsal Striatum.

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Ito, Makoto; Doya, Kenji

2015-11-01

Previous theoretical studies of animal and human behavioral learning have focused on the dichotomy of the value-based strategy using action value functions to predict rewards and the model-based strategy using internal models to predict environmental states. However, animals and humans often take simple procedural behaviors, such as the "win-stay, lose-switch" strategy without explicit prediction of rewards or states. Here we consider another strategy, the finite state-based strategy, in which a subject selects an action depending on its discrete internal state and updates the state depending on the action chosen and the reward outcome. By analyzing choice behavior of rats in a free-choice task, we found that the finite state-based strategy fitted their behavioral choices more accurately than value-based and model-based strategies did. When fitted models were run autonomously with the same task, only the finite state-based strategy could reproduce the key feature of choice sequences. Analyses of neural activity recorded from the dorsolateral striatum (DLS), the dorsomedial striatum (DMS), and the ventral striatum (VS) identified significant fractions of neurons in all three subareas for which activities were correlated with individual states of the finite state-based strategy. The signal of internal states at the time of choice was found in DMS, and for clusters of states was found in VS. In addition, action values and state values of the value-based strategy were encoded in DMS and VS, respectively. These results suggest that both the value-based strategy and the finite state-based strategy are implemented in the striatum.

Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

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Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting

2016-10-05

An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

Identification of QTLs for grain yield and grain-related traits of maize (Zea mays L.) using an AFLP-map, different testers, and cofactor analysis

NARCIS (Netherlands)

Ajimone Marsan, P.; Gorni, C.; Chitto, A.; Redaelli, R.; Vijk, van R.; Stam, P.; Motto, M.

2001-01-01

Abstract We exploited the AFLP?1(AFLP? is a registered trademark of Keygene, N.V.) technique to map and characterise quantitative trait loci (QTLs) for grain yield and two grain-related traits of a maize segregating population. Two maize elite inbred lines were crossed to produce 229 F2 individuals

Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts

DEFF Research Database (Denmark)

Cumming, P; Danielsen, E H; Vafaee, M

2001-01-01

, both pre-synaptic markers of dopamine fibres were normal in striatum. Dopamine depletion or grafting were without effect on the cerebral perfusion rate, measured with [15O]-water, did not alter the rate of oxygen metabolism (CMRO2) in brain, and did not alter the binding potential of tracers...... for dopamine D1 or D2 receptors in pig striatum. However, the grafting was associated with a local increase in the binding of [11C]PK 11195, a tracer for reactive gliosis, suggesting that an immunological reaction occurs at the site of graft, which might potentially have reduced the graft patency. However...

Topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus).

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Ashwell, K W S

2008-09-01

The topography and chemoarchitecture of the striatum and pallidum in a monotreme, the short-beaked echidna (Tachyglossus aculeatus) have been studied using Nissl staining in conjunction with myelin staining, enzyme reactivity to acetylcholinesterase and NADPH diaphorase, and immunoreactivity to parvalbumin, calbindin, calretinin, tyrosine hydroxylase, neuropeptide Y, and neurofilament protein (SMI-32 antibody). All those components of the striatum and pallidum found in eutherian mammals could also be identified in the echidna's brain, with broad chemoarchitectural similarities to those regions in eutherian brains also apparent. There was a clear chemoarchitectural gradient visible with parvalbumin immunoreactivity of neurons and fibers, suggesting a subdivision of the echidna caudatoputamen into weakly reactive rostrodorsomedial and strongly reactive caudoventrolateral components. This may, in turn, relate to subdivision into associative versus sensorimotor CPu and reflect homology to the caudate and putamen of primates. Moreover, the chemoarchitecture of the echidna striatum suggested the presence of striosome-matrix architecture. The morphology of identified neuronal groups (i.e., parvalbumin, calbindin, and neuropeptide Y immunoreactive) in the echidna striatum and pallidum showed many similarities to those seen in eutherians, although the pattern of distribution of calbindin immunoreactive neurons was more uniform in the caudatoputamen of the echidna than in therians. These observations indicate that the same broad features of striatal and pallidal organization apply across all mammals and suggest that these common features may have arisen before the divergence of the monotreme and therian lineages.

A RAD-Based Genetic Map for Anchoring Scaffold Sequences and Identifying QTLs in Bitter Gourd (Momordica charantia)

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Cui, Junjie; Luo, Shaobo; Niu, Yu; Huang, Rukui; Wen, Qingfang; Su, Jianwen; Miao, Nansheng; He, Weiming; Dong, Zhensheng; Cheng, Jiaowen; Hu, Kailin

2018-01-01

Genetic mapping is a basic tool necessary for anchoring assembled scaffold sequences and for identifying QTLs controlling important traits. Though bitter gourd (Momordica charantia) is both consumed and used as a medicinal, research on its genomics and genetic mapping is severely limited. Here, we report the construction of a restriction site associated DNA (RAD)-based genetic map for bitter gourd using an F2 mapping population comprising 423 individuals derived from two cultivated inbred lines, the gynoecious line ‘K44’ and the monoecious line ‘Dali-11.’ This map comprised 1,009 SNP markers and spanned a total genetic distance of 2,203.95 cM across the 11 linkage groups. It anchored a total of 113 assembled scaffolds that covered about 251.32 Mb (85.48%) of the 294.01 Mb assembled genome. In addition, three horticulturally important traits including sex expression, fruit epidermal structure, and immature fruit color were evaluated using a combination of qualitative and quantitative data. As a result, we identified three QTL/gene loci responsible for these traits in three environments. The QTL/gene gy/fffn/ffn, controlling sex expression involved in gynoecy, first female flower node, and female flower number was detected in the reported region. Particularly, two QTLs/genes, Fwa/Wr and w, were found to be responsible for fruit epidermal structure and white immature fruit color, respectively. This RAD-based genetic map promotes the assembly of the bitter gourd genome and the identified genetic loci will accelerate the cloning of relevant genes in the future. PMID:29706980

A RAD-Based Genetic Map for Anchoring Scaffold Sequences and Identifying QTLs in Bitter Gourd (Momordica charantia

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Junjie Cui

2018-04-01

Full Text Available Genetic mapping is a basic tool necessary for anchoring assembled scaffold sequences and for identifying QTLs controlling important traits. Though bitter gourd (Momordica charantia is both consumed and used as a medicinal, research on its genomics and genetic mapping is severely limited. Here, we report the construction of a restriction site associated DNA (RAD-based genetic map for bitter gourd using an F2 mapping population comprising 423 individuals derived from two cultivated inbred lines, the gynoecious line ‘K44’ and the monoecious line ‘Dali-11.’ This map comprised 1,009 SNP markers and spanned a total genetic distance of 2,203.95 cM across the 11 linkage groups. It anchored a total of 113 assembled scaffolds that covered about 251.32 Mb (85.48% of the 294.01 Mb assembled genome. In addition, three horticulturally important traits including sex expression, fruit epidermal structure, and immature fruit color were evaluated using a combination of qualitative and quantitative data. As a result, we identified three QTL/gene loci responsible for these traits in three environments. The QTL/gene gy/fffn/ffn, controlling sex expression involved in gynoecy, first female flower node, and female flower number was detected in the reported region. Particularly, two QTLs/genes, Fwa/Wr and w, were found to be responsible for fruit epidermal structure and white immature fruit color, respectively. This RAD-based genetic map promotes the assembly of the bitter gourd genome and the identified genetic loci will accelerate the cloning of relevant genes in the future.

Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

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Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

2014-01-01

Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

5HT2A receptor blockade in dorsomedial striatum reduces repetitive behaviors in BTBR mice.

Science.gov (United States)

Amodeo, D A; Rivera, E; Cook, E H; Sweeney, J A; Ragozzino, M E

2017-03-01

Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT 2A receptor activity is altered in autism, while recent work indicates that systemic 5HT 2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT 2A receptors are expressed in the orbitofrontal cortex and striatum. These two regions have been shown to be altered in autism. The present study investigated whether 5HT 2A receptor blockade in the dorsomedial striatum or orbitofrontal cortex in the BTBR mouse strain, an idiopathic model of autism, affects the phenotype related to restricted and repetitive behaviors. Microinfusion of the 5HT 2A receptor antagonist, M100907 into the dorsomedial striatum alleviated a reversal learning impairment and attenuated grooming behavior. M100907 infusion into the orbitofrontal cortex increased perseveration during reversal learning and potentiated grooming. These findings suggest that increased 5HT 2A receptor activity in the dorsomedial striatum may contribute to behavioral inflexibility and stereotyped behaviors in the BTBR mouse. 5HT 2A receptor signaling in the orbitofrontal cortex may be critical for inhibiting a previously learned response during reversal learning and expression of stereotyped behavior. The present results suggest which brain areas exhibit abnormalities underlying repetitive behaviors in an idiopathic mouse model of autism, as well as which brain areas systemic treatment with M100907 may principally act on in BTBR mice to attenuate repetitive behaviors. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

Science.gov (United States)

Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

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Christina Coughlan

2015-01-01

Full Text Available Epidemiological studies indicate exposures to the herbicide paraquat (PQ and fungicide maneb (MB are associated with increased risk of Parkinson’s disease (PD. Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg, MB (30 mg/kg, or the combination of PQ and MB (PQMB. Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.

Change of striatum dopaminergic transporter and content of dopamine in rats with experimental hyperthyroidism

International Nuclear Information System (INIS)

Lin Yansong; Wang Huicheng; Zhao Zhiying; Zhu Li; Zhang Yingqiang; Chen Zhengping

2009-01-01

Objective: The central dopamine system plays an important role in regulating movement and mood. In our routine clinical practice,we found that patients with hyperthyroidism often show tremor of their hands or legs. Meanwhile they also experienced emotional problems such as anxiety and depression. These reminded us that there might be close relationship between thyroid hormone and dopamine system. Based on our previous works, in this study we evaluated the change of striatum dopamine transporter (DAT) by using 99 Tc m -2β- [N, N'-bis (2-merecaptoethyl) ethylenediamino]methyl, 3β- (4-chlorophenyl) tropane (TRODAT-1) brain biodistribution, and the content of striatum dopamine and its metabolites 3.4-di-hydroxyphenylacetic (DOPAC) by high performace liquid chromatograph-electrochemical detection (HPLC-ECD) in rats with experimental hyperthyroidism. Methods: All 24 rats were randomly divided into two groups, thyroxin group were induced by daily thyroxin infusion for 14 d to be experimental hyperthyroidism, the others were control group which received saline infusion. The blood samples were randomly taken from thyroxine group and control group, and the concentration of TT 3 and TT 4 were detected by radioimmunoassay. After 14 d,both experimental (thyroxine group) and control group were further divided into 2 sub-groups. One was for evaluation of the function of striatum DAT by 99 Tc m -TRODAT-1 biodistribution study and the other was for HPIJC-ECD measurement of the concentration of dopamine and its metabolites DOPAC. Results: Significantly hyperactivity and weight loss [(223.90 ± 8.40) VS (261.60 ± 14.20)g, t=6.98. P 3 and TT 4 after thyroxin infusion was significantly elevated than that of before thyroxin infusion [(2.72 ± 0.29) V8(1.46 ± 0.17) nmol/L, t=10.51, P 3 , and TT 4 after saline infusion showed no statistical significance as compared with before saline infusion [(1.71 ± 0.20) vs (1.54 ± O.09) nmol/L, t=1.68. P>0.05 and (88.38 ± 6.76) vs (98.38 ± 9

Functional Specialization within the Striatum along Both the Dorsal/Ventral and Anterior/Posterior Axes during Associative Learning via Reward and Punishment

Science.gov (United States)

Mattfeld, Aaron T.; Gluck, Mark A.; Stark, Craig E. L.

2011-01-01

The goal of the present study was to elucidate the role of the human striatum in learning via reward and punishment during an associative learning task. Previous studies have identified the striatum as a critical component in the neural circuitry of reward-related learning. It remains unclear, however, under what task conditions, and to what…

SELEKSI RUMPUT LAUT Kappaphycus striatum DALAM UPAYA PENINGKATAN LAJU PERTUMBUHAN BIBIT UNTUK BUDIDAYA

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Andi Parenrengi

2017-01-01

Full Text Available Budidaya rumput laut di Indonesia semakin berkembang seiring dengan peningkatan permintaan bahan baku industri untuk pasar domestik dan eksport. Rumput laut Kappaphycus striatum, salah satu spesies rumput laut komersil, telah intensif dibudidayakan di perairan pantai. Saat ini, masalah utama yang dihadapi pembudidaya adalah rendahnya kualitas bibit yang berasal dari hasil budidaya. Seleksi varietas merupakan salah satu metode yang diharapkan dapat meningkatkan laju pertumbuhan rumput laut. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh seleksi varietas terhadap pertumbuhan rumput laut sehingga dapat dilakukan produksi bibit unggul untuk keperluan budidaya. Budidaya rumput laut K. striatum telah dilakukan di Teluk Laikang, Kabupaten Takalar, Provinsi Sulawesi Selatan dengan menggunakan metode long line. Seleksi varietas dilakukan berdasarkan parameter laju pertumbuhan harian (LPH dan metode seleksi mengacu pada protokol seleksi yang telah dikembangkan pada rumput laut K. alvarezii. Hasil penelitian menunjukkan bahwa LPH bibit hasil seleksi lebih tinggi (P

Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

Science.gov (United States)

Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

2008-04-01

Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

Haloperidol-induced changes in neuronal activity in the striatum of the freely moving rat

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Dorin eYael

2013-12-01

Full Text Available The striatum is the main input structure of the basal ganglia, integrating input from the cerebral cortex and the thalamus, which is modulated by midbrain dopaminergic input. Dopamine modulators, including agonists and antagonists, are widely used to relieve motor and psychiatric symptoms in a variety of pathological conditions. Haloperidol, a dopamine D2 antagonist, is commonly used in multiple psychiatric conditions and motor abnormalities. This article reports the effects of haloperidol on the activity of three major striatal subpopulations: medium spiny projection neurons (MSNs, fast spiking interneurons (FSIs and tonically active neurons (TANs. We implanted multi-wire electrode arrays in the rat dorsal striatum and recorded the activity of multiple single units in freely moving animals before and after systemic haloperidol injection. Haloperidol decreased the firing rate of FSIs and MSNs while increasing their tendency to fire in an oscillatory manner in the high voltage spindle (HVS frequency range of 7-9 Hz. Haloperidol led to an increased firing rate of TANs but did not affect their non-oscillatory firing pattern and their typical correlated firing activity. Our results suggest that dopamine plays a key role in tuning both single unit activity and the interactions within and between different subpopulations in the striatum in a differential manner. These findings highlight the heterogeneous striatal effects of tonic dopamine regulation via D2 receptors which potentially enable the treatment of diverse pathological states associated with basal ganglia dysfunction.

Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum.

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Mattsson, Anna; Olson, Lars; Svensson, Torgny H; Schilström, Björn

2007-11-01

Cholinergic dysfunction has been implicated as a putative contributing factor in the pathogenesis of schizophrenia. Recently, we showed that cholinergic denervation of the neocortex in adult rats leads to a marked increase in the behavioral response to amphetamine. The main objective of this study was to investigate if the enhanced locomotor response to amphetamine seen after cortical cholinergic denervation was paralleled by an increased amphetamine-induced release of dopamine in the nucleus accumbens and/or striatum. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of adult rats. Amphetamine-induced dopamine release in the nucleus accumbens or striatum was monitored by in vivo microdialysis 2 to 3 weeks after lesioning. We found that cholinergic denervation of the rat neocortex leads to a significantly increased amphetamine-induced dopamine release in the nucleus accumbens. Interestingly, the cholinergic lesion did not affect amphetamine-induced release of dopamine in the striatum. The enhanced amphetamine-induced dopamine release in the nucleus accumbens in the cholinergically denervated rats could be reversed by administration of the muscarinic agonist oxotremorine, but not nicotine, prior to the amphetamine challenge, suggesting that loss of muscarinic receptor stimulation is likely to have caused the observed effect. The results suggest that abnormal responsiveness of dopamine neurons can be secondary to cortical cholinergic deficiency. This, in turn, might be of relevance for the pathophysiology of schizophrenia and provides a possible link between cholinergic disturbances and alteration of dopamine transmission.

Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

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Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

2018-04-15

Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum.

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Taylor, S B; Anglin, J M; Paode, P R; Riggert, A G; Olive, M F; Conrad, C D

2014-11-07

Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after 2 weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Ventral striatum activation to prosocial rewards predicts longitudinal declines in adolescent risk taking.

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Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Galván, Adriana

2013-01-01

Adolescence is a period of intensified emotions and an increase in motivated behaviors and passions. Evidence from developmental neuroscience suggests that this heightened emotionality occurs, in part, due to a peak in functional reactivity to rewarding stimuli, which renders adolescents more oriented toward reward-seeking behaviors. Most prior work has focused on how reward sensitivity may create vulnerabilities, leading to increases in risk taking. Here, we test whether heightened reward sensitivity may potentially be an asset for adolescents when engaged in prosocial activities. Thirty-two adolescents were followed over a one-year period to examine whether ventral striatum activation to prosocial rewards predicts decreases in risk taking over a year. Results show that heightened ventral striatum activation to prosocial stimuli relates to longitudinal declines in risk taking. Therefore, the very same neural region that has conferred vulnerability for adolescent risk taking may also be protective against risk taking. Copyright © 2012 Elsevier Ltd. All rights reserved.

Natural variation in partial resistance to Pseudomonas syringae is controlled by two major QTLs in Arabidopsis thaliana.

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Laure Perchepied

Full Text Available BACKGROUND: Low-level, partial resistance is pre-eminent in natural populations, however, the mechanisms underlying this form of resistance are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used the model pathosystem Pseudomonas syringae pv. tomato DC3000 (Pst - Arabidopsis thaliana to study the genetic basis of this form of resistance. Phenotypic analysis of a set of Arabidopsis accessions, based on evaluation of in planta pathogen growth revealed extensive quantitative variation for partial resistance to Pst. It allowed choosing a recombinant inbred line (RIL population derived from a cross between the accessions Bayreuth and Shahdara for quantitative genetic analysis. Experiments performed under two different environmental conditions led to the detection of two major and two minor quantitative trait loci (QTLs governing partial resistance to Pst and called PRP-Ps1 to PRP-Ps4. The two major QTLs, PRP-Ps1 and PRP-Ps2, were confirmed in near isogenic lines (NILs, following the heterogeneous inbred families (HIFs strategy. Analysis of marker gene expression using these HIFs indicated a negative correlation between the induced amount of transcripts of SA-dependent genes PR1, ICS and PR5, and the in planta bacterial growth in the HIF segregating at PRP-Ps2 locus, suggesting an implication of PRP-Ps2 in the activation of SA dependent responses. CONCLUSIONS/SIGNIFICANCE: These results show that variation in partial resistance to Pst in Arabidopsis is governed by relatively few loci, and the validation of two major loci opens the way for their fine mapping and their cloning, which will improve our understanding of the molecular mechanisms underlying partial resistance.

Prior Cocaine Self-Administration Increases Response-Outcome Encoding That Is Divorced from Actions Selected in Dorsal Lateral Striatum.

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Burton, Amanda C; Bissonette, Gregory B; Zhao, Adam C; Patel, Pooja K; Roesch, Matthew R

2017-08-09

Dorsal lateral striatum (DLS) is a highly associative structure that encodes relationships among environmental stimuli, behavioral responses, and predicted outcomes. DLS is known to be disrupted after chronic drug abuse; however, it remains unclear what neural signals in DLS are altered. Current theory suggests that drug use enhances stimulus-response processing at the expense of response-outcome encoding, but this has mostly been tested in simple behavioral tasks. Here, we investigated what neural correlates in DLS are affected by previous cocaine exposure as rats performed a complex reward-guided decision-making task in which predicted reward value was independently manipulated by changing the delay to or size of reward associated with a response direction across a series of trial blocks. After cocaine self-administration, rats exhibited stronger biases toward higher-value reward and firing in DLS more strongly represented action-outcome contingencies independent from actions subsequently taken rather than outcomes predicted by selected actions (chosen-outcome contingencies) and associations between stimuli and actions (stimulus-response contingencies). These results suggest that cocaine self-administration strengthens action-outcome encoding in rats (as opposed to chosen-outcome or stimulus-response encoding), which abnormally biases behavior toward valued reward when there is a choice between two options during reward-guided decision-making. SIGNIFICANCE STATEMENT Current theories suggest that the impaired decision-making observed in individuals who chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome (R-O) and stimulus-response associations, respectively. We examined the impact that prior cocaine self-administration had on firing in dorsal lateral striatum (DLS), a brain area known to be involved in habit formation and affected by drugs of abuse

Deficits in water maze performance and oxidative stress in the hippocampus and striatum induced by extremely low frequency magnetic field exposure.

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Yonghua Cui

Full Text Available The exposures to extremely low frequency magnetic field (ELF-MF in our environment have dramatically increased. Epidemiological studies suggest that there is a possible association between ELF-MF exposure and increased risks of cardiovascular disease, cancers and neurodegenerative disorders. Animal studies show that ELF-MF exposure may interfere with the activity of brain cells, generate behavioral and cognitive disturbances, and produce deficits in attention, perception and spatial learning. Although, many research efforts have been focused on the interaction between ELF-MF exposure and the central nervous system, the mechanism of interaction is still unknown. In this study, we examined the effects of ELF-MF exposure on learning in mice using two water maze tasks and on some parameters indicative of oxidative stress in the hippocampus and striatum. We found that ELF-MF exposure (1 mT, 50 Hz induced serious oxidative stress in the hippocampus and striatum and impaired hippocampal-dependent spatial learning and striatum-dependent habit learning. This study provides evidence for the association between the impairment of learning and the oxidative stress in hippocampus and striatum induced by ELF-MF exposure.

A high-density genetic map for anchoring genome sequences and identifying QTLs associated with dwarf vine in pumpkin (Cucurbita maxima Duch.).

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Zhang, Guoyu; Ren, Yi; Sun, Honghe; Guo, Shaogui; Zhang, Fan; Zhang, Jie; Zhang, Haiying; Jia, Zhangcai; Fei, Zhangjun; Xu, Yong; Li, Haizhen

2015-12-24

Pumpkin (Cucurbita maxima Duch.) is an economically important crop belonging to the Cucurbitaceae family. However, very few genomic and genetic resources are available for this species. As part of our ongoing efforts to sequence the pumpkin genome, high-density genetic map is essential for anchoring and orienting the assembled scaffolds. In addition, a saturated genetic map can facilitate quantitative trait locus (QTL) mapping. A set of 186 F2 plants derived from the cross of pumpkin inbred lines Rimu and SQ026 were genotyped using the genotyping-by-sequencing approach. Using the SNPs we identified, a high-density genetic map containing 458 bin-markers was constructed, spanning a total genetic distance of 2,566.8 cM across the 20 linkage groups of C. maxima with a mean marker density of 5.60 cM. Using this map we were able to anchor 58 assembled scaffolds that covered about 194.5 Mb (71.7%) of the 271.4 Mb assembled pumpkin genome, of which 44 (183.0 Mb; 67.4%) were oriented. Furthermore, the high-density genetic map was used to identify genomic regions highly associated with an important agronomic trait, dwarf vine. Three QTLs on linkage groups (LGs) 1, 3 and 4, respectively, were recovered. One QTL, qCmB2, which was located in an interval of 0.42 Mb on LG 3, explained 21.4% phenotypic variations. Within qCmB2, one gene, Cma_004516, encoding the gibberellin (GA) 20-oxidase in the GA biosynthesis pathway, had a 1249-bp deletion in its promoter in bush type lines, and its expression level was significantly increased during the vine growth and higher in vine type lines than bush type lines, supporting Cma_004516 as a possible candidate gene controlling vine growth in pumpkin. A high-density pumpkin genetic map was constructed, which was used to successfully anchor and orient the assembled genome scaffolds, and to identify QTLs highly associated with pumpkin vine length. The map provided a valuable resource for gene cloning and marker assisted breeding in pumpkin and

The First Genetic and Comparative Map of White Lupin (Lupinus albus L.): Identification of QTLs for Anthracnose Resistance and Flowering Time, and a Locus for Alkaloid Content

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Phan, Huyen T. T.; Ellwood, Simon R.; Adhikari, Kedar; Nelson, Matthew N.; Oliver, Richard P.

2007-01-01

Abstract We report the first genetic linkage map of white lupin (Lupinus albus L.). An F8 recombinant inbred line population developed from Kiev mutant × P27174 was mapped with 220 amplified fragment length polymorphism and 105 gene-based markers. The genetic map consists of 28 main linkage groups (LGs) that varied in length from 22.7 cM to 246.5 cM and spanned a total length of 2951 cM. There were seven additional pairs and 15 unlinked markers, and 12.8% of markers showed segregation distortion at P anthracnose resistance, flowering time, and alkaloid content allowed loci governing these traits to be defined. Two quantitative trait loci (QTLs) with significant effects were identified for anthracnose resistance on LG4 and LG17, and two QTLs were detected for flowering time on the top of LG1 and LG3. Alkaloid content was mapped as a Mendelian trait to LG11. PMID:17526914

Identification of Functional Clusters in the Striatum Using Infinite Relational Modeling

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Andersen, Kasper Winther; Madsen, Kristoffer Hougaard; Siebner, Hartwig

2011-01-01

In this paper we investigate how the Infinite Relational Model can be used to infer functional groupings of the human striatum using resting state fMRI data from 30 healthy subjects. The Infinite Relational Model is a non-parametric Bayesian method for infering community structure in complex netw...... and non-links in the graphs as missing. We find that the model is performing well above chance for all subjects....

Efferent projections of the dorsal ventricular ridge and the striatum in the Tegu lizard. Tupinambis nigropunctatus.

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Voneida, T J; Sligar, C M

1979-07-01

A H3 proline-leucine mixture was injected into the dorsal ventricular ridge (DVR) and striatum of the Tegu lizard in order to determine their efferent projections. The brains were processed according to standard radioautographic technique, and counterstained with cresyl violet. DVR projections were generally restricted to the telencephalon, while striatal projections were limited to diencephalic and mesencephalic structures. Thus the anterior DVR projects ipsilaterally to nuclei sphericus and lateralis amygdalae, striatum (ipsilateral and contralateral) ventromedial nucleus of the hypothalamus, nucleus accumbens, anterior olfactory nucleus, nucleus of the lateral olfactory tract and lateral pallium. Posterior DVR projections enter ipsilateral anterior olfactory nucleus, lateral and interstitial amygdalar nuclei, olfactory tubercle and bulb, nucleus of the lateral olfactory tract and a zone surrounding the ventromedial hypothalamic nucleus. Labeled axons from striatal injections pass caudally in the lateral forebrain bundle to enter (via dorsal peduncle) nuclei dorsomedialis, medialis posterior, entopeduncularis anterior, and a zone surrounding nucleus rotundus. Others join the ventral peduncle of LFB and enter ventromedial nucleus (thalami), while the remaining fibers continue caudally in the ventral peduncle to the mesencephalic prerubral field, central gray, substantia nigra, nucleus intercollicularis, reticular formation and pretectal nucleus posterodorsalis. These results are discussed in relation to the changing notions regarding terminology, classification and functions of dorsl ventricular ridge and striatum.

Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

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Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

2014-12-01

Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

Glucose Injections into the Dorsal Hippocampus or Dorsolateral Striatum of Rats Prior to T-Maze Training: Modulation of Learning Rates and Strategy Selection

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Canal, Clinton E.; Stutz, Sonja J.; Gold, Paul E.

2005-01-01

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial…

Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.

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Xue, Bing; Chen, Elton C; He, Nan; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

2017-01-01

Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs. In addition, D1R and D2R coactivation recruited GluA1 and PKA preferentially to extrasynaptic sites. In sum, our in vivo data support an existence of a dynamic DA-ACh balance in the striatum which actively modulates GluA1 AMPAR phosphorylation and trafficking. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional inactivation of dorsal medial striatum alters behavioral flexibility and recognition process in mice.

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Qiao, Yanhua; Wang, Xingyue; Ma, Lian; Li, Shengguang; Liang, Jing

2017-10-01

Deficits in behavioral flexibility and recognition memory are commonly observed in mental illnesses and neurodegenerative diseases. Abnormality of the striatum has been implicated in an association with the pathology of these diseases. However, the exact roles of striatal heterogeneous structures in these cognitive functions are still unknown. In the present study, we investigated the effects of suppressing neuronal activity in the dorsomedial striatum (DMStr) and nucleus accumbens core (NAcC) on reversal learning and novelty recognition in mice. In addition, the locomotor activity, anxiety-like behavior and social interaction were analyzed. Neuronal inactivation was performed by expressing lentivirus-mediated tetanus toxin (TeNT) in the target regions. The results showed that reversal learning was facilitated by neuronal inactivation in the DMStr but not the NAcC, which was attributable to accelerated extinction of acquired strategy but not to impaired memory retention. Furthermore, mice with NAcC inactivation spent more time exploring a novel object than a familiar one, comparable to control mice. In contrast, mice with DMStr inactivation exhibited no preference to a novel environment during the novel object or place recognition test. The DMStr mice also exhibited decreased anxiety level. No phenotypic effect was observed in the locomotion or social interaction in mice with either DMStr or NAcC inactivation. Altogether, these findings suggest that the DMStr but not the ventral area of the striatum plays a crucial role in learning and memory by coordinating spatial exploration as well as mediating information updating. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala and ventral striatum

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Fletcher, PC; Napolitano, A; Skeggs, A; Miller, SR; Delafont, B; Cambridge, VC; de Wit, S; Nathan, PJ; Brooke, A; O’Rahilly, S; Farooqi, IS; Bullmore, ET

2012-01-01

We used fMRI to explore brain responses to food images in overweight humans, examining independently the impact of a pre-scan meal (“satiety”) and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus and ventral striatum. Each region was specifically responsive to high calorie compared to low calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine) while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behaviour and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug’s impact on both weight and subsequently-measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad lib eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally-specific effect on brain function through which sibutramine exerts its clinical effect. PMID:20980590

A common neural code for social and monetary rewards in the human striatum.

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Wake, Stephanie J; Izuma, Keise

2017-10-01

Although managing social information and decision making on the basis of reward is critical for survival, it remains uncertain whether differing reward type is processed in a uniform manner. Previously, we demonstrated that monetary reward and the social reward of good reputation activated the same striatal regions including the caudate nucleus and putamen. However, it remains unclear whether overlapping activations reflect activities of identical neuronal populations or two overlapping but functionally independent neuronal populations. Here, we re-analyzed the original data and addressed this question using multivariate-pattern-analysis and found evidence that in the left caudate nucleus and bilateral nucleus accumbens, social vs monetary reward were represented similarly. The findings suggest that social and monetary rewards are processed by the same population of neurons within these regions of the striatum. Additional findings demonstrated similar neural patterns when participants experience high social reward compared to viewing others receiving low social reward (potentially inducing schadenfreude). This is possibly an early indication that the same population of neurons may be responsible for processing two different types of social reward (good reputation and schadenfreude). These findings provide a supplementary perspective to previous research, helping to further elucidate the mechanisms behind social vs non-social reward processing. © The Author (2017). Published by Oxford University Press.

Different involvement of medial prefrontal cortex and dorso-lateral striatum in automatic and controlled processing of a future conditioned stimulus.

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Pérez-Díaz, Francisco; Díaz, Estrella; Sánchez, Natividad; Vargas, Juan Pedro; Pearce, John M; López, Juan Carlos

2017-01-01

Recent studies support the idea that stimulus processing in latent inhibition can vary during the course of preexposure. Controlled attentional mechanisms are said to be important in the early stages of preexposure, while in later stages animals adopt automatic processing of the stimulus to be used for conditioning. Given this distinction, it is possible that both types of processing are governed by different neural systems, affecting differentially the retrieval of information about the stimulus. In the present study we tested if a lesion to the dorso-lateral striatum or to the medial prefrontal cortex has a selective effect on exposure to the future conditioned stimulus (CS). With this aim, animals received different amounts of exposure to the future CS. The results showed that a lesion to the medial prefrontal cortex enhanced latent inhibition in animals receiving limited preexposure to the CS, but had no effect in animals receiving extended preexposure to the CS. The lesion of the dorso-lateral striatum produced a decrease in latent inhibition, but only in animals with an extended exposure to the future conditioned stimulus. These results suggest that the dorsal striatum and medial prefrontal cortex play essential roles in controlled and automatic processes. Automatic attentional processes appear to be impaired by a lesion to the dorso-lateral striatum and facilitated by a lesion to the prefrontal cortex.

Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

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Kishida, Kenneth T.; Saez, Ignacio; Lohrenz, Terry; Witcher, Mark R.; Laxton, Adrian W.; Tatter, Stephen B.; White, Jason P.; Ellis, Thomas L.; Phillips, Paul E. M.; Montague, P. Read

2016-01-01

In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons. PMID:26598677

Genome-Wide Association Mapping Reveals Multiple QTLs Governing Tolerance Response for Seedling Stage Chilling Stress in Indica Rice

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Sharat K. Pradhan

2017-04-01

Full Text Available Rice crop is sensitive to cold stress at seedling stage. A panel of population representing 304 shortlisted germplasm lines was studied for seedling stage chilling tolerance in indica rice. Six phenotypic classes were exposed to six low temperature stress regimes under control phenotyping facility to investigate response pattern. A panel of 66 genotypes representing all phenotypic classes was used for ensuring genetic diversity, population structure and association mapping for the trait using 58 simple sequence repeat (SSR and 2 direct trait linked markers. A moderate level of genetic diversity was detected in the panel population for the trait. Deviation of Hardy-Weinberg's expectation was detected in the studied population using Wright's F statistic. The panel showed 30% variation among population and 70% among individuals. The entire population was categorized into three sub-populations through STRUCTURE analysis. This revealed tolerance for the trait had a common primary ancestor for each sub-population with few admix individuals. The panel population showed the presence of many QTLs for cold stress tolerance in the individuals representing like genome-wide expression of the trait. Nineteen SSR markers were significantly associated at chilling stress of 8°C to 4°C for 7–21 days duration. Thus, the primers linked to the seedling stage cold tolerance QTLs namely qCTS9, qCTS-2, qCTS6.1, qSCT2, qSCT11, qSCT1a, qCTS-3.1, qCTS11.1, qCTS12.1, qCTS-1b, and CTB2 need to be pyramided for development of strongly chilling tolerant variety.

A multivariate surface-based analysis of the putamen in premature newborns: regional differences within the ventral striatum.

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Jie Shi

Full Text Available Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

NARCIS (Netherlands)

Holz, N.E.; Boecker-Schlier, R.; Buchmann, A.F.; Blomeyer, D.; Jennen-Steinmetz, C.; Baumeister, S.; Plichta, M.M.; Cattrell, A.; Schumann, G.; Esser, G.; Schmidt, M.; Buitelaar, J.K.; Meyer-Lindenberg, A.; Banaschewski, T.; Brandeis, D.; Laucht, M.

2017-01-01

Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

NARCIS (Netherlands)

Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernández, G.

2017-01-01

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

Stress induces a shift towards striatum-dependent stimulus-response learning via the mineralocorticoid receptor

NARCIS (Netherlands)

Vogel, S.; Klumpers, F.; Navarro Schröder, T.; Oplaat, K.T.; Krugers, H.J.; Oitzl, M.S.; Joëls, M.; Doeller, C.F.; Fernandez, G.

2017-01-01

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

NARCIS (Netherlands)

Vogel, Susanne; Klumpers, Floris; Schroeder, Tobias Navarro; Oplaat, Krista T.; Krugers, Harm J.; Oitzl, Melly S.; Joels, Marian; Doeller, Christian F.; Fernandez, Guillen

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this

Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex.

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Dere, E; Zheng-Fischhöfer, Q; Viggiano, D; Gironi Carnevale, U A; Ruocco, L A; Zlomuzica, A; Schnichels, M; Willecke, K; Huston, J P; Sadile, A G

2008-05-02

Neuronal gap junctions in the brain, providing intercellular electrotonic signal transfer, have been implicated in physiological and behavioral correlates of learning and memory. In connexin31.1 (Cx31.1) knockout (KO) mice the coding region of the Cx31.1 gene was replaced by a LacZ reporter gene. We investigated the impact of Cx31.1 deficiency on open-field exploration, the behavioral response to an odor, non-selective attention, learning and memory performance, and the levels of memory-related proteins in the hippocampus, striatum and the piriform cortex. In terms of behavior, the deletion of the Cx31.1 coding DNA in the mouse led to increased exploratory behaviors in a novel environment, and impaired one-trial object recognition at all delays tested. Despite strong Cx31.1 expression in the peripheral and central olfactory system, Cx31.1 KO mice exhibited normal behavioral responses to an odor. We found increased levels of acetylcholine esterase (AChE) and cAMP response element-binding protein (CREB) in the striatum of Cx31.1 KO mice. In the piriform cortex the Cx31.1 KO mice had an increased heterogeneity of CREB expression among neurons. In conclusion, gap-junctions featuring the Cx31.1 protein might be involved in open-field exploration as well as object memory and modulate levels of AChE and CREB in the striatum and piriform cortex.

Cocaine self-administration differentially affects allosteric A2A-D2 receptor-receptor interactions in the striatum. Relevance for cocaine use disorder.

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Pintsuk, Julia; Borroto-Escuela, Dasiel O; Pomierny, Bartosz; Wydra, Karolina; Zaniewska, Magdalena; Filip, Malgorzata; Fuxe, Kjell

2016-05-01

In the current study behavioral and biochemical experiments were performed to study changes in the allosteric A2AR-D2R interactions in the ventral and dorsal striatum after cocaine self-administration versus corresponding yoked saline control. By using ex vivo [(3)H]-raclopride/quinpirole competition experiments, the effects of the A2AR agonist CGS 21680 (100 nM) on the KiH and KiL values of the D2-like receptor (D2-likeR) were determined. One major result was a significant reduction in the D2-likeR agonist high affinity state observed with CGS 21680 after cocaine self-administration in the ventral striatum compared with the yoked saline group. The results therefore support the hypothesis that A2AR agonists can at least in part counteract the motivational actions of cocaine. This action is mediated via the D2-likeR by targeting the A2AR protomer of A2AR-D2-like R heteroreceptor complexes in the ventral striatum, which leads to the reduction of D2-likeR protomer recognition through the allosteric receptor-receptor interaction. In contrast, in the dorsal striatum the CGS 21680-induced antagonistic modulation in the D2-likeR agonist high affinity state was abolished after cocaine self-administration versus the yoked saline group probably due to a local dysfunction/disruption of the A2AR-D2-like R heteroreceptor complexes. Such a change in the dorsal striatum in cocaine self-administration can contribute to the development of either locomotor sensitization, habit-forming learning and/or the compulsive drug seeking by enhanced D2-likeR protomer signaling. Potential differences in the composition and stoichiometry of the A2AR-D2R heteroreceptor complexes, including differential recruitment of sigma 1 receptor, in the ventral and dorsal striatum may explain the differential regional changes observed in the A2A-D2-likeR interactions after cocaine self-administration. Copyright © 2016 Elsevier Inc. All rights reserved.

Reward Anticipation in Ventral Striatum and Individual Sensitivity to Reward: A Pilot Study of a Child-Friendly fMRI Task.

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van Hulst, Branko M; de Zeeuw, Patrick; Lupas, Kellina; Bos, Dienke J; Neggers, Sebastiaan F W; Durston, Sarah

2015-01-01

Reward processing has been implicated in developmental disorders. However, the classic task to probe reward anticipation, the monetary incentive delay task, has an abstract coding of reward and no storyline and may therefore be less appropriate for use with developmental populations. We modified the task to create a version appropriate for use with children. We investigated whether this child-friendly version could elicit ventral striatal activation during reward anticipation in typically developing children and young adolescents (aged 9.5-14.5). In addition, we tested whether our performance-based measure of reward sensitivity was associated with anticipatory activity in ventral striatum. Reward anticipation was related to activity in bilateral ventral striatum. Moreover, we found an association between individual reward sensitivity and activity in ventral striatum. We conclude that this task assesses ventral striatal activity in a child-friendly paradigm. The combination with a performance-based measure of reward sensitivity potentially makes the task a powerful tool for developmental imaging studies of reward processing.

Vasogenic edema in striatum following ingestion of glufosinate-containing herbicide.

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Lee, Hui-Young; Song, Seo-Young; Lee, Seung-Hwan; Lee, Seo-Young; Kim, Sung-Hun; Ryu, Sook-Won

2009-10-01

Glufosinate-ammonium (GLA) is a broad-spectrum herbicide used worldwide. We report a patient who attempted suicide by ingesting a liquid herbicide containing GLA. A diffusion-weighted MRI showed cytotoxic edema in the hippocampus as well as vasogenic edema in the striata. To our knowledge, vasogenic edema caused by GLA-containing herbicide involving the striatum has not been reported in association with cytotoxic edema in the hippocampus. We assume that this herbicide affected the central nervous system via different mechanisms to produce both cytotoxic and vasogenic edema in the same patient.

Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

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Tobón-Velasco, J C; Palafox-Sánchez, Victoria; Mendieta, Liliana; García, E; Santamaría, A; Chamorro-Cevallos, G; Limón, I Daniel

2013-08-01

There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 μg/2 μL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.

Electrical high frequency stimulation in the dorsal striatum: Effects on response learning and on GABA levels in rats.

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Schumacher, Anett; de Vasconcelos, Anne Pereira; Lecourtier, Lucas; Moser, Andreas; Cassel, Jean-Christophe

2011-09-23

Electrical high frequency stimulation (HFS) has been used to treat various neurological and psychiatric diseases. The striatal area contributes to response learning and procedural memory. Therefore, we investigated the effect of striatal HFS application on procedural/declarative-like memory in rats. All rats were trained in a flooded Double-H maze for three days (4 trials/day) to swim to an escape platform hidden at a constant location. The starting place was the same for all trials. After each training session, HFS of the left dorsal striatum was performed over 4h in alternating 20 min periods (during rest time, 10a.m. to 3p.m.). Nineteen hours after the last HFS and right after a probe trial assessing the rats' strategy (procedural vs. declarative-like memory-based choice), animals were sacrificed and the dorsal striatum was quickly removed. Neurotransmitter levels were measured by HPLC. Stimulated rats did not differ from sham-operated and control rats in acquisition performance, but exhibited altered behavior during the probe trial (procedural memory responses being less frequent than in controls). In stimulated rats, GABA levels were significantly increased in the dorsal striatum on both sides. We suggest that HFS of the dorsal striatum does not alter learning behavior in rats but influences the strategy by which the rats solve the task. Given that the HFS-induced increase of GABA levels was found 19 h after stimulation, it can be assumed that HFS has consequences lasting for several hours and which are functionally significant at a behavioral level, at least under our stimulation (frequency, timing, location, side and strength of stimulation) and testing conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

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Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W

2012-06-20

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

Paralimbic system and striatum are involved in motivational behavior.

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Nishimura, Masahiko; Yoshii, Yoshihiko; Watanabe, Jobu; Ishiuchi, Shogo

2009-10-28

Goal-directed rewarded behavior and goal-directed non-rewarded behavior are concerned with motivation. However, the neural substrates involved in goal-directed non-rewarded behaviors are unknown. Using functional magnetic resonance imaging, we investigated the brain activities of healthy individuals during a novel tool use (turning a screwdriver) to elucidate the relationship between the brain mechanism relevant to goal-directed non-rewarded behavior and motivation. We found that our designed behavioral task evoked activities in the orbitofrontal cortex, striatum, anterior insula, lateral prefrontal cortex, and anterior cingulate cortex compared with a meaningless task. These results suggest that activation in these cerebral regions play important roles in motivational behavior without tangible rewards.

Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat.

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Zhou, Ligang; Furuta, Takahiro; Kaneko, Takeshi

2004-12-06

Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. 2004 Wiley-Liss, Inc.

Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

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Aisa N. Chepkova

2015-01-01

Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.

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Pfabigan, Daniela M; Seidel, Eva-Maria; Sladky, Ronald; Hahn, Andreas; Paul, Katharina; Grahl, Arvina; Küblböck, Martin; Kraus, Christoph; Hummer, Allan; Kranz, Georg S; Windischberger, Christian; Lanzenberger, Rupert; Lamm, Claus

2014-08-01

The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. Copyright © 2014. Published by Elsevier Inc.

Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

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Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

2001-05-01

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

International Nuclear Information System (INIS)

Esquifino, A.I.; Seara, R.; Fernandez-Rey, E.; Lafuente, A.

2001-01-01

This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

Exploration of D2 receptors and content of DA of striatum in hemi-parkinsonism model rats before and after madopar treatment

International Nuclear Information System (INIS)

Lin Yansong; Lin Xiangtong

1998-01-01

125 I-IBZM autoradiographic analysis, HPLC-ECD were used to study the relationship between D 2 receptors and the content of DA, HVA, DOPAC in striatum of hemi-parkinsonism model rats before and after Madopar treatment. After Madopar treatment, the striatum/cerebellum 125 I-IBZM uptake ratio of lesioned side was 7.23 +- 0.67, showed 17.22 +- 3.94% increasing as compared to the contralateral side, the increasing were significantly declined compared with the pretreatment group and control group (P 2 receptors

Genetic and biochemical analysis reveals linked QTLs determining natural variation for fruit post-harvest water loss in pepper (Capsicum).

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Popovsky-Sarid, Sigal; Borovsky, Yelena; Faigenboim, Adi; Parsons, Eugene P; Lohrey, Gregory T; Alkalai-Tuvia, Sharon; Fallik, Elazar; Jenks, Matthew A; Paran, Ilan

2017-02-01

Molecular markers linked to QTLs controlling post-harvest fruit water loss in pepper may be utilized to accelerate breeding for improved shelf life and inhibit over-ripening before harvest. Bell pepper (Capsicum annuum L.) is an important vegetable crop world-wide. However, marketing is limited by the relatively short shelf life of the fruit due to water loss and decay that occur during prolonged storage. Towards breeding pepper with reduced fruit post-harvest water loss (PWL), we studied the genetic, physiological and biochemical basis for natural variation of PWL. We performed quantitative trait locus (QTL) mapping of fruit PWL in multiple generations of an interspecific cross of pepper, which resulted in the identification of two linked QTLs on chromosome 10 that control the trait. We further developed near-isogenic lines (NILs) for characterization of the QTL effects. Transcriptome analysis of the NILs allowed the identification of candidate genes associated with fruit PWL-associated traits such as cuticle biosynthesis, cell wall metabolism and fruit ripening. Significant differences in PWL between the NILs in the immature fruit stage, differentially expressed cuticle-associated genes and differences in the content of specific chemical constituents of the fruit cuticle, indicated a likely influence of cuticle composition on the trait. Reduced PWL in the NILs was associated with delayed over-ripening before harvest, low total soluble solids before storage, and reduced fruit softening after storage. Our study enabled a better understanding of the genetic and biological processes controlling natural variation in fruit PWL in pepper. Furthermore, the genetic materials and molecular markers developed in this study may be utilized to breed peppers with improved shelf life and inhibited over-ripening before harvest.

Motor Planning under Unpredictable Reward: Modulations of Movement Vigor and Primate Striatum Activity

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Ioan eOpris

2011-05-01

Full Text Available Although reward probability is an important factor that shapes animal behavior, it is not well understood however, how the primate brain translates reward expectation into the vigor of movement (reaction time and speed. To address this question, we trained two monkeys in a reaction time task that required wrist movements in response to vibrotactile and visual stimuli, with a variable reward schedule. Correct performance was rewarded in 75 % of the trials. Monkeys were certain that they would be rewarded only in the trials immediately following withheld rewards. In these trials, the animals responded sooner and moved faster. Single-unit recordings from the dorsal striatum revealed that modulations in striatal neurons reflected such modulations of movement vigor. First, in the trials with certain rewards, striatal neurons modulated their firing rates earlier. Second, magnitudes of changes in neuronal firing rates depended on whether or not monkeys were certain about the reward. Third, these modulations depended on the sensory modality of the cue (visual vs. vibratory and/or movement direction (flexions vs. extensions. We conclude that dorsal striatum may be a part of the mechanism responsible for the modulation of movement vigor in response to changes of reward predictability.

Altered dopaminergic regulation of the dorsal striatum is able to induce tic-like movements in juvenile rats

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Rizzo, Francesca; Boeckers, Tobias; Schulze, Ulrike

2018-01-01

Motor tics are sudden, repetitive, involuntary movements representing the hallmark behaviors of the neurodevelopmental disease Tourette’s syndrome (TS). The primary cause of TS remains unclear. The initial observation that dopaminergic antagonists alleviate tics led to the development of a dopaminergic theory of TS etiology which is supported by post mortem and in vivo studies indicating that non-physiological activation of the striatum could generate tics. The striatum controls movement execution through the balanced activity of dopamine receptor D1 and D2-expressing medium spiny neurons of the direct and indirect pathway, respectively. Different neurotransmitters can activate or repress striatal activity and among them, dopamine plays a major role. In this study we introduced a chronic dopaminergic alteration in juvenile rats, in order to modify the delicate balance between direct and indirect pathway. This manipulation was done in the dorsal striatum, that had been associated with tic-like movements generation in animal models. The results were movements resembling tics, which were categorized and scored according to a newly developed rating scale and were reduced by clonidine and riluzole treatment. Finally, post mortem analyses revealed altered RNA expression of dopaminergic receptors D1 and D2, suggesting an imbalanced dopaminergic regulation of medium spiny neuron activity as being causally related to the observed phenotype. PMID:29698507

Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

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Snyder-Keller, A; Costantini, L C; Graber, D J

2001-01-01

Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

Genetic architecture of palm oil fatty acid composition in cultivated oil palm (Elaeis guineensis Jacq.) compared to its wild relative E. oleifera (H.B.K) Cortés.

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Montoya, Carmenza; Cochard, Benoit; Flori, Albert; Cros, David; Lopes, Ricardo; Cuellar, Teresa; Espeout, Sandra; Syaputra, Indra; Villeneuve, Pierre; Pina, Michel; Ritter, Enrique; Leroy, Thierry; Billotte, Norbert

2014-01-01

We searched for quantitative trait loci (QTL) associated with the palm oil fatty acid composition of mature fruits of the oil palm E. guineensis Jacq. in comparison with its wild relative E. oleifera (H.B.K) Cortés. The oil palm cross LM2T x DA10D between two heterozygous parents was considered in our experiment as an intraspecific representative of E. guineensis. Its QTLs were compared to QTLs published for the same traits in an interspecific Elaeis pseudo-backcross used as an indirect representative of E. oleifera. Few correlations were found in E. guineensis between pulp fatty acid proportions and yield traits, allowing for the rather independent selection of both types of traits. Sixteen QTLs affecting palm oil fatty acid proportions and iodine value were identified in oil palm. The phenotypic variation explained by the detected QTLs was low to medium in E. guineensis, ranging between 10% and 36%. The explained cumulative variation was 29% for palmitic acid C16:0 (one QTL), 68% for stearic acid C18:0 (two QTLs), 50% for oleic acid C18:1 (three QTLs), 25% for linoleic acid C18:2 (one QTL), and 40% (two QTLs) for the iodine value. Good marker co-linearity was observed between the intraspecific and interspecific Simple Sequence Repeat (SSR) linkage maps. Specific QTL regions for several traits were found in each mapping population. Our comparative QTL results in both E. guineensis and interspecific materials strongly suggest that, apart from two common QTL zones, there are two specific QTL regions with major effects, which might be one in E. guineensis, the other in E. oleifera, which are independent of each other and harbor QTLs for several traits, indicating either pleiotropic effects or linkage. Using QTL maps connected by highly transferable SSR markers, our study established a good basis to decipher in the future such hypothesis at the Elaeis genus level.

Genetic Architecture of Palm Oil Fatty Acid Composition in Cultivated Oil Palm (Elaeis guineensis Jacq.) Compared to Its Wild Relative E. oleifera (H.B.K) Cortés

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Montoya, Carmenza; Cochard, Benoit; Flori, Albert; Cros, David; Lopes, Ricardo; Cuellar, Teresa; Espeout, Sandra; Syaputra, Indra; Villeneuve, Pierre; Pina, Michel; Ritter, Enrique; Leroy, Thierry; Billotte, Norbert

2014-01-01

We searched for quantitative trait loci (QTL) associated with the palm oil fatty acid composition of mature fruits of the oil palm E. guineensis Jacq. in comparison with its wild relative E. oleifera (H.B.K) Cortés. The oil palm cross LM2T x DA10D between two heterozygous parents was considered in our experiment as an intraspecific representative of E. guineensis. Its QTLs were compared to QTLs published for the same traits in an interspecific Elaeis pseudo-backcross used as an indirect representative of E. oleifera. Few correlations were found in E. guineensis between pulp fatty acid proportions and yield traits, allowing for the rather independent selection of both types of traits. Sixteen QTLs affecting palm oil fatty acid proportions and iodine value were identified in oil palm. The phenotypic variation explained by the detected QTLs was low to medium in E. guineensis, ranging between 10% and 36%. The explained cumulative variation was 29% for palmitic acid C16:0 (one QTL), 68% for stearic acid C18:0 (two QTLs), 50% for oleic acid C18:1 (three QTLs), 25% for linoleic acid C18:2 (one QTL), and 40% (two QTLs) for the iodine value. Good marker co-linearity was observed between the intraspecific and interspecific Simple Sequence Repeat (SSR) linkage maps. Specific QTL regions for several traits were found in each mapping population. Our comparative QTL results in both E. guineensis and interspecific materials strongly suggest that, apart from two common QTL zones, there are two specific QTL regions with major effects, which might be one in E. guineensis, the other in E. oleifera, which are independent of each other and harbor QTLs for several traits, indicating either pleiotropic effects or linkage. Using QTL maps connected by highly transferable SSR markers, our study established a good basis to decipher in the future such hypothesis at the Elaeis genus level. PMID:24816555

Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

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Baker, Phillip M.; Ragozzino, Michael E.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

Identification of QTLs for resistance to sclerotinia stem rot and BnaC.IGMT5.a as a candidate gene of the major resistant QTL SRC6 in Brassica napus.

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Jian Wu

Full Text Available Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus, is one of the most devastating fungal diseases and imposes huge yield loss each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR at the mature plant stage and three QTLs for leaf resistance (LR at the seedling stage in multiple environments were mapped on nine linkage groups (LGs of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790 was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.

Reinforcement learning signals in the human striatum distinguish learners from nonlearners during reward-based decision making.

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Schönberg, Tom; Daw, Nathaniel D; Joel, Daphna; O'Doherty, John P

2007-11-21

The computational framework of reinforcement learning has been used to forward our understanding of the neural mechanisms underlying reward learning and decision-making behavior. It is known that humans vary widely in their performance in decision-making tasks. Here, we used a simple four-armed bandit task in which subjects are almost evenly split into two groups on the basis of their performance: those who do learn to favor choice of the optimal action and those who do not. Using models of reinforcement learning we sought to determine the neural basis of these intrinsic differences in performance by scanning both groups with functional magnetic resonance imaging. We scanned 29 subjects while they performed the reward-based decision-making task. Our results suggest that these two groups differ markedly in the degree to which reinforcement learning signals in the striatum are engaged during task performance. While the learners showed robust prediction error signals in both the ventral and dorsal striatum during learning, the nonlearner group showed a marked absence of such signals. Moreover, the magnitude of prediction error signals in a region of dorsal striatum correlated significantly with a measure of behavioral performance across all subjects. These findings support a crucial role of prediction error signals, likely originating from dopaminergic midbrain neurons, in enabling learning of action selection preferences on the basis of obtained rewards. Thus, spontaneously observed individual differences in decision making performance demonstrate the suggested dependence of this type of learning on the functional integrity of the dopaminergic striatal system in humans.

The role of the dorsal striatum in extinction: A memory systems perspective.

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Goodman, Jarid; Packard, Mark G

2018-04-01

The present review describes a role for the dorsal striatum in extinction. Evidence from brain lesion and pharmacological studies indicate that the dorsolateral region of the striatum (DLS) mediates extinction in various maze learning and instrumental learning tasks. Within the context of a multiple memory systems view, the role of the DLS in extinction appears to be selective. Specifically, the DLS mediates extinction of habit memory and is not required for extinction of cognitive memory. Thus, extinction mechanisms mediated by the DLS may involve response-produced inhibition (e.g. inhibition of existing stimulus-response associations or formation of new inhibitory stimulus-response associations), as opposed to cognitive mechanisms (e.g. changes in expectation). Evidence also suggests that NMDA-dependent forms of synaptic plasticity may be part of the mechanism through which the DLS mediates extinction of habit memory. In addition, in some learning situations, DLS inactivation enhances extinction, suggesting a competitive interaction between multiple memory systems during extinction training. Consistent with a multiple memory systems perspective, it is suggested that the DLS represents one of several distinct neural systems that specialize in extinction of different kinds of memory. The relevance of these findings to the development of behavioral and pharmacological therapies that target the maladaptive habit-like symptoms in human psychopathology is also briefly considered. Published by Elsevier Inc.

Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

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Mariana Raineri

Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain

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Ferré, S.; Diamond, I.; Goldberg, S.R.; Yao, L.; Hourani, S.M.O.; Huang, Z.L.; Urade, Y.; Kitchen, I.

2007-01-01

Adenosine A2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A receptors. A2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A2A receptor knockout mice suggest that A2A receptor antagonists might have some therapeutic potential in pain states, in particular where

Materials as regard about ecology and spreading of lycodine striatum bicolor nik in Tajikistan

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Sattorov, T.S.; Khidirov, Kh.; Mukhammadkulov, M.

2003-01-01

In this article is placed new scientific information about biology, ecology and spreading of Lycodine striatum bicolor within the territory of Tajikistan. Finding available in this article concerning spreading of flus snake are considered to be new. This scarce snake was discovered for the first time in Northern part of Tajikistan. This new information will enrich our notions about Reptile fauna of Tajikistan

The usefulness of fractional anisotropy maps in localization of lacunar infractions in striatum, internal capsule and thalamus

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Jeong, H.K.; Lee, S.K.; Kim, D.I. [Dept. of Radiology and Research, Yonsei University Coll. of Medicine, Seoul (Korea); JHeo, J.H. [Dept. of Neurology, Yonsei University Coll. of Medicine, Seoul (Korea)

2005-04-01

We aimed in this study to assess the clinical usefulness of fractional anisotropy (FA) maps in the evaluation of lacunar infractions in striatum, internal capsule and thalamus. We retrospectively reviewed 28 patients (18 mean, 10 women; mean age 63 years) who had acute lacunar infraction in striatum, internal capsule and thalamus on diffusion weighted MR imaging (DWI). Fractional anisotropy (FA) maps were generated in addition to conventional T2 weigthed images (T2WI) and trace masp of DWI. Two radiologists reviewed the location of infraction was determined by FA maps. i.e. on the white band of internal capsule. Accuracy and inter-observer agreement on determination of the location of interfraction was evaluated. Accuracy of infract localization by T2WI-DWI only was varied from 72 to 91% according to the observers. Inter-observer agreement value was moderate (Kappa=0.446), when images were interpreted by T2WI-DWI only. Clinical manifestation of each lesions wre varied, but sensory motor stroke was mainly observed in thalamic lesion (50%) while pure motor hemiparesis was predominant in the case of infract involving internal capsule, corona radiata (91%) and basal ganglia (83%). The FA maps is useful in the evaluation of lacunar lesions in striatum, internal capsule and thalamus. Clinical presentation varies according to the exact location of lacunar infractions, and more accurate diagnosis can be made by FA maps as well as conventional T2-weighted image and DWI.

Ventral Striatum Functional Connectivity as a Predictor of Adolescent Depressive Disorder in a Longitudinal Community-Based Sample.

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Pan, Pedro Mario; Sato, João R; Salum, Giovanni A; Rohde, Luis A; Gadelha, Ary; Zugman, Andre; Mari, Jair; Jackowski, Andrea; Picon, Felipe; Miguel, Eurípedes C; Pine, Daniel S; Leibenluft, Ellen; Bressan, Rodrigo A; Stringaris, Argyris

2017-11-01

Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.

Comparison of four methods of measurement on [11C]Raclopride  binding potential using regional specificity in the striatum

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Peterson, Ericka; Gjedde, Albert; Møller, Arne

Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus  accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs...... as reference for all three methods. Mean pB were calculated for left and right putamen, caudate and VST. Correlations between the left and right pB were examined for each striatal region. The results of the three methods were also compared. Results: For all three methods, there was a highly significant...... correlation between the left and right caudate and putamen (pVST (0.01

Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age

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James N. Porter

2015-02-01

Full Text Available The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns and dorsal anterior cingulate cortex (dACC that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model

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Aidt, Frederik Heurlin; Nielsen, Signe Marie Borch; Kanters, Jørgen

2013-01-01

Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system...

Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats.

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Haleagrahara, Nagaraja; Siew, Cheng Jun; Ponnusamy, Kumar

2013-02-01

The catecholaminergic neurotoxin 6-hydroxydopamine is used to lesion dopaminergic pathways in the experimental animal models of Parkinson's disease. The present study was aimed to evaluate the combined treatment with bioflavonoid quercetin (QN) and desferrioxamine (DFO) on 6-hydroxydopamine (6-OHDA) - induced neurotoxicity in the striatum of rats. Adult, male Sprague - Dawley rats were divided into control, sham lesion, 6-OHDA treated (300 µg, intracisternal), 6-OHDA with QN (50 mg/kg) treated, 6-OHDA with DFO (50 mg/kg) treated and 6-OHDA with QN and DFO treated groups. Striatal dopamine, protein carbonyl content (PCC), glutathione (GSH) and superoxide dismutase (SOD) were estimated. There was a significant increase (p protection. Combined treatment has a more significant effect (p protecting the neurons and increasing the antioxidant enzymes in the striatum. In conclusion, an antioxidant with iron chelator treatment showed a significant neuroprotective effect against 6-hydroxydopamine (6-OHDA) by preventing dopaminergic neuronal loss and maintaining the striatal dopamine level.

A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

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McDonald, R J; Hong, N S

2004-01-01

This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

CB1 cannabinoid receptor expression in the striatum: Association with corticostriatal circuits and developmental regulation

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Vincent eVan Waes

2012-03-01

Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

Genes and quality trait loci (QTLs) associated with firmness in Malus x domestica

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Marondedze, Claudius

2013-03-31

Fruit firmness, a quality quantitative trait, has long been established as a key textural property and one of the essential parameters for estimating ripening and shelf life of apples. Loss of firmness, also referred to as fruit softening, is undesirable in apples and represents a serious problem for growers in many countries. This results in the reduction of apple shelf life and in turn influences its commercialization. Low firmness impacts negatively on the sensory values of juiciness, crunchiness and crispness. Fruit firmness is affected by the inheritance of alleles at multiple loci and their possible interactions with the environment. Identification of these loci is key for the determination of genetic candidate markers that can be implemented in marker assisted selection and breeding for trees and/or cultivars that can yield firmer fruits with economic value. In turn, this technique can help reduce the time needed to evaluate plants and new cultivars could become available faster. This review provides an overview of quantitative trait loci (QTL), including additional putative QTLs that we have identified, and genes associated with firmness and their importance to biotechnology, the breeding industry and eventually the consumers.

Identification of quantitative trait loci underlying seed protein content of soybean including main, epistatic, and QTL × environment effects in different regions of Northeast China.

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Teng, Weili; Li, Wen; Zhang, Qi; Wu, Depeng; Zhao, Xue; Li, Haiyan; Han, Yingpeng; Li, Wenbin

2017-08-01

The objective here was to identify QTL underlying soybean protein content (PC), and to evaluate the additive and epistatic effects of the QTLs. A mapping population, consisting of 129 recombinant inbred lines (RILs), was created by crossing 'Dongnong 46' and 'L-100'. Phenotypic data of the parents and RILs were collected for 4 years in three locations of Heilongjiang Province of China. A total of 213 SSR markers were used to construct a genetic linkage map. Eight QTLs, located on seven chromosomes (Chr), were identified to be associated with PC among the 10 tested environments. Of the seven QTLs, five QTLs, qPR-2 (Satt710, on Chr9), qPR-3 (Sat_122, on Chr12), qPR-5 (Satt543, on Chr17), qPR-7 (Satt163, on Chr18), and qPR-8 (Satt614, on Chr20), were detected in six, seven, seven, six, and seven environments, respectively, implying relatively stable QTLs. qPR-3 could explain 3.33%-11.26% of the phenotypic variation across eight tested environments. qPR-5 and qPR-8 explained 3.64%-10.1% and 11.86%-18.40% of the phenotypic variation, respectively, across seven tested environments. Eight QTLs associated with PC exhibited additive and (or) additive × environment interaction effects. The results showed that environment-independent QTLs often had higher additive effects. Moreover, five epistatic pairwise QTLs were identified in the 10 environments.

Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

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Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

2012-01-01

Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

Response inhibition signals and miscoding of direction in dorsomedial striatum

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Daniel W Bryden

2012-09-01

Full Text Available The ability to inhibit action is critical for everyday behavior and is affected by a variety of disorders. Behavioral control and response inhibition is thought to depend on a neural circuit that includes the dorsal striatum, yet the neural signals that lead to response inhibition and its failure are unclear. To address this issue, we recorded from neurons in rat dorsomedial striatum (mDS in a novel task in which rats responded to a spatial cue that signaled that reward would be delivered either to the left or to the right. On 80% of trials rats were instructed to respond in the direction cued by the light (GO. On 20% of trials a second light illuminated instructing the rat to refrain from making the cued movement and move in the opposite direction (STOP. Many neurons in mDS encoded direction, firing more or less strongly for GO movements made ipsilateral or contralateral to the recording electrode. Neurons that fired more strongly for contralateral GO responses were more active when rats were faster, showed reduced activity on STOP trials, and miscoded direction on errors, suggesting that when these neurons were overly active, response inhibition failed. Neurons that decreased firing for contralateral movement were excited during trials in which the rat was required to stop the ipsilateral movement. For these neurons activity was reduced when errors were made and was negatively correlated with movement time suggesting that when these neurons were less active on STOP trials, response inhibition failed. Finally, the activity of a significant number of neurons represented a global inhibitory signal, firing more strongly during response inhibition regardless of response direction. Breakdown by cell type suggests that putative medium spiny neurons tended to fire more strongly under STOP trials, whereas putative interneurons exhibited both activity patterns. 

Dopamine release in ventral striatum during Iowa Gambling Task performance is associated with increased excitement levels in pathological gambling

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Linnet, Jakob; Møller, Arne; Peterson, Ericka

2011-01-01

Aims Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls. Design Pathological Gamblers...... and Healthy Controlswere experimentally compared in a non-gambling (baseline) and gambling condition. Measurements We used Positron Emission Tomography (PET) with the tracer raclopride to measure dopamine D 2/3 receptor availability in the ventral striatum during a non-gambling and gambling condition...... of the Iowa GamblingTask (IGT). After each condition participants rated their excitement level. Setting Laboratory experiment. Participants 18 Pathological Gamblers and 16 Healthy Controls. Findings Pathological Gamblers with dopamine release in the ventral striatum had significantly higher excitement levels...

MicroRNA-124 slows down the progression of Huntington′s disease by promoting neurogenesis in the striatum

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Tian Liu

2015-01-01

Full Text Available MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington′s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington′s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington′s disease transgenic mouse in the rotarod test. 5-Bromo-2′-deoxyuridine (BrdU staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington′s disease possibly through its important role in neuronal differentiation and survival.

Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease.

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Choi, Chi-Bong; Kim, Sang-Young; Lee, Sung-Ho; Jahng, Geon-Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung-Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo-Suk

2011-01-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication. Copyright © 2011 Elsevier Inc. All rights reserved.

Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze

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Gardner, Robert S.; Suarez, Daniel F.; Robinson-Burton, Nadira K.; Rudnicky, Christopher J.; Gulati, Asish; Ascoli, Giorgio A.; Dumas, Theodore C.

2016-01-01

The strategies utilized to effectively perform a given task change with practice and experience. During a spatial navigation task, with relatively little training, performance is typically attentive enabling an individual to locate the position of a goal by relying on spatial landmarks. These (place) strategies require an intact hippocampus. With task repetition, performance becomes automatic; the same goal is reached using a fixed response or sequence of actions. These (response) strategies require an intact striatum. The current work aims to understand the activation patterns across these neural structures during this experience-dependent strategy transition. This was accomplished by region-specific measurement of activity-dependent immediate early gene expression among rats trained to different degrees on a dual-solution task (i.e., a task that can be solved using either place or response navigation). As expected, rats increased their reliance on response navigation with extended task experience. In addition, dorsal hippocampal expression of the immediate early gene Arc was considerably reduced in rats that used a response strategy late in training (as compared with hippocampal expression in rats that used a place strategy early in training). In line with these data, vicarious trial and error, a behavior linked to hippocampal function, also decreased with task repetition. Although Arc mRNA expression in dorsal medial or lateral striatum alone did not correlate with training stage, the ratio of expression in the medial striatum to that in the lateral striatum was relatively high among rats that used a place strategy early in training as compared with the ratio among over-trained response rats. Altogether, these results identify specific changes in the activation of dissociated neural systems that may underlie the experience-dependent emergence of response-based automatic navigation. PMID:26976088

Inability to acquire spatial information and deploy spatial search strategies in mice with lesions in dorsomedial striatum.

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Pooters, Tine; Gantois, Ilse; Vermaercke, Ben; D'Hooge, Rudi

2016-02-01

Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of motion correction for dynamic [11C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun; Choe, Yearn Seong; Kang, Eun Joo

2005-01-01

Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [ 11 C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion correction

Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum.

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Allen, Jeremy P; Hathway, Gareth J; Clarke, Neil J; Jowett, Mike I; Topps, Stephanie; Kendrick, Keith M; Humphrey, Patrick P A; Wilkinson, Lawrence S; Emson, Piers C

2003-05-01

The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.

A High-Density Integrated DArTseq SNP-Based Genetic Map of Pisum fulvum and Identification of QTLs Controlling Rust Resistance

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Eleonora Barilli

2018-02-01

Full Text Available Pisum fulvum, a wild relative of pea is an important source of allelic diversity to improve the genetic resistance of cultivated species against fungal diseases of economic importance like the pea rust caused by Uromyces pisi. To unravel the genetic control underlying resistance to this fungal disease, a recombinant inbred line (RIL population was generated from a cross between two P. fulvum accessions, IFPI3260 and IFPI3251, and genotyped using Diversity Arrays Technology. A total of 9,569 high-quality DArT-Seq and 8,514 SNPs markers were generated. Finally, a total of 12,058 markers were assembled into seven linkage groups, equivalent to the number of haploid chromosomes of P. fulvum and P. sativum. The newly constructed integrated genetic linkage map of P. fulvum covered an accumulated distance of 1,877.45 cM, an average density of 1.19 markers cM−1 and an average distance between adjacent markers of 1.85 cM. The composite interval mapping revealed three QTLs distributed over two linkage groups that were associated with the percentage of rust disease severity (DS%. QTLs UpDSII and UpDSIV were located in the LGs II and IV respectively and were consistently identified both in adult plants over 3 years at the field (Córdoba, Spain and in seedling plants under controlled conditions. Whenever they were detected, their contribution to the total phenotypic variance varied between 19.8 and 29.2. A third QTL (UpDSIV.2 was also located in the LGIVand was environmentally specific as was only detected for DS % in seedlings under controlled conditions. It accounted more than 14% of the phenotypic variation studied. Taking together the data obtained in the study, it could be concluded that the expression of resistance to fungal diseases in P. fulvum originates from the resistant parent IFPI3260.

Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

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Kim, Hannah; Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Yunjin; Kang, Minkyung; Kim, Kyoung-Shim; Han, Pyung-Lim

2014-11-07

Behavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices. Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes. Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such

Effect of Paullinia cupana Mart. Commercial Extract During the Aging of Middle Age Wistar Rats: Differential Effects on the Hippocampus and Striatum.

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Mingori, Moara Rodrigues; Heimfarth, Luana; Ferreira, Charles Francisco; Gomes, Henrique Mautone; Moresco, Karla Suzana; Delgado, Jeferson; Roncato, Sabrina; Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

2017-08-01

During aging, there is a marked decline in the antioxidant capacity of brain tissue, leading to a gradual loss of the antioxidant/oxidant balance, which causes oxidative damage. The effects of Paullinia cupana Mart. extract, which is described as being rich in caffeine and many polyphenol compounds, on the central nervous system have not been extensively investigated. The aim of this study was to therefore investigate the effect of a commercial guarana extract (CGE) on cognitive function, oxidative stress, and brain homeostasis proteins related to cognitive injury and senescence in middle age, male Wistar rats. Animals were randomly assigned to a group according to their treatment (saline, CGE, or caffeine). Solutions were administered daily by oral gavage for 6 months. Open field and novel object recognition tasks were performed before and after treatment. Biochemical analyses were carried out on the hippocampus and striatum. Our open field data showed an increase in exploratory activity and a decrease in anxiety-like behavior with caffeine but not with the CGE treatment. In the CGE-treated group, catalase activity decreased in the hippocampus and increased in the striatum. Analyses of the hippocampus and striatum indicate that CGE and/or caffeine altered some of the analyzed parameters in a tissue-specific manner. Our data suggest that CGE intake does not improve cognitive development, but modifies the oxidative stress machinery and neurodegenerative-signaling pathway, inhibiting pro-survival pathway molecules in the hippocampus and striatum. This may contribute to the development of unfavorable microenvironments in the brain and neurodegenerative disorders.

Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

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Monica S Guzman

2011-11-01

Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

Effect of ligustrazine on levels of amino acid neurotransmitters in rat striatum after cerebral ischemia-reperfusion injury.

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Han, Jin; Wan, Hai-Tong; Yang, Jie-Hong; Zhang, Yu-Yan; Ge, Li-Jun; Bie, Xiao-Dong

2014-01-01

This study aimed to evaluate the effect of ligustrazine on levels of amino acid transmitters in the extracellular fluid of striatum following cerebral ischemia/reperfusion (I/R) in male Sprague-Dawley rats. A microdialysis cannula guide was implanted into the right striatum. After recovery, animals underwent a sham operation or middle cerebral artery occlusion (MCAO). Those that developed cerebral ischemia after MCAO were randomized to receive propylene glycol salt water and ligustrazine respectively. Striatal fluid samples were collected from all animals at 15-min intervals after treatment and were subjected to HPLC analysis of aspartic acid, glutamic acid, taurine, and γ-amino butyric acid. Upon the last sample collection, animals were sacrificed and brain tissue specimens were collected for triphenyltetrazolium chloride staining and NeuN staining. Compared with the sham operation, MCAO induced significant neurological deficits and increased striatal concentrations of the four neurotransmitters assessed in a time-dependent manner (P cerebral infarction-protective agent may have potential clinical implications for I/R-related brain damage.

Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

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Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

2012-03-23

Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

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Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

2011-12-01

Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

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Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

2017-05-01

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs.

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Cherel, Pierre; Pires, José; Glénisson, Jérôme; Milan, Denis; Iannuccelli, Nathalie; Hérault, Frédéric; Damon, Marie; Le Roy, Pascale

2011-08-29

Detection of quantitative trait loci (QTLs) affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08), with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the influence of major-effect mutations on the least affected

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs

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Iannuccelli Nathalie

2011-08-01

Full Text Available Abstract Background Detection of quantitative trait loci (QTLs affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08, with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Results Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Conclusions Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the

Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

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Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

2016-01-11

Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and

Molecular and functional definition of the developing human striatum.

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Onorati, Marco; Castiglioni, Valentina; Biasci, Daniele; Cesana, Elisabetta; Menon, Ramesh; Vuono, Romina; Talpo, Francesca; Laguna Goya, Rocio; Lyons, Paul A; Bulfamante, Gaetano P; Muzio, Luca; Martino, Gianvito; Toselli, Mauro; Farina, Cinthia; Barker, Roger A; Biella, Gerardo; Cattaneo, Elena

2014-12-01

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal genes, including those encoding transcription factors, that distinguished striatal from neocortical identities. Unexpected differences from mouse striatal development were discovered. We monitored 36 determinants at the protein level, revealing regional domains of expression and their refinement, during striatal development. We electrophysiologically profiled human striatal neurons differentiated in vitro and determined their refined molecular and functional properties. These results provide a resource and opportunity to gain global understanding of how transcriptional and functional processes converge to specify human striatal and neocortical neurons during development.

Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

NARCIS (Netherlands)

Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Fenske, Sabrina; Schirmbeck, Frederike; Englisch, Susanne; Schilling, Claudia; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

2015-01-01

Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be

Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum.

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Peter J Clark

Full Text Available Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress. Impaired escape behavior is a result of stress-sensitized serotonin (5-HT neuron activity in the dorsal raphe (DRN and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS and lateral (DLS dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.

Effects of motion correction for dynamic [{sup 11}C]Raclopride brain PET data on the evaluation of endogenous dopamine release in striatum

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Lee, Jae Sung; Kim, Yu Kyeong; Cho, Sang Soo; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Choe, Yearn Seong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kang, Eun Joo [Kangwon University, Chunchon (Korea, Republic of)

2005-10-15

Neuroreceptor PET studies require 60-120 minutes to complete and head motion of the subject during the PET scan increases the uncertainty in measured activity. In this study, we investigated the effects of the data-driven head motion correction on the evaluation of endogenous dopamine release (DAR) in the striatum during the motor task which might have caused significant head motion artifact. [{sup 11}C]raclopride PET scans on 4 normal volunteers acquired with bolus plus constant infusion protocol were retrospectively analyzed. Following the 50 min resting period, the participants played a video game with a momentary reward for 40 min. Dynamic frames acquired during the equilibrium condition (pre-task: 30-50 min, task: 70-90 min, post-task:110-120 min) were realigned to the first frame in pre-task condition. Intra-condition registrations between the frames were performed, and average image for each condition was created and registered to the pre-task image (inter-condition registration). Pre-task PET image was then co-registered to own MRI of each participant and transformation parameters were reapplied to the others. Volumes of interest (VOI) for dorsal putamen (PU) and caudate (CA), ventral striatum (VS), and cerebellum were defined on the MRI. Binding potential (BP) was measured and DAR was calculated as the percent change of BP during and after the task. SPM analyses on the BP parametric images were also performed to explore the regional difference in the effects of head motion on BP and DAR estimation. Changes in position and orientation of the striatum during the PET scans were observed before the head motion correction. BP values at pre-task condition were not changed significantly after the intra-condition registration. However, the BP values during and after the task and DAR were significantly changed after the correction. SPM analysis also showed that the extent and significance of the BP differences were significantly changed by the head motion

Cerebral Oxygenation of the Cortex and Striatum following Normobaric Hyperoxia and Mild Hypoxia in Rats by EPR Oximetry using Multi-Probe Implantable Resonators

Science.gov (United States)

Hou, Huagang; Li, Hongbin; Dong, Ruhong; Mupparaju, Sriram; Khan, Nadeem; Swartz, Harold

2013-01-01

Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO2) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO2 was measured simultaneously in the cerebral cortex and striatum in the same rats before, during, and after normobaric hyperoxia and mild hypoxia challenges. The baseline mean tissue pO2 values (±SE) were not significantly different between the cortex and striatum. During 30 min of 100% O2 inhalation, a statistically significant increase in tissue pO2 of all four sites was observed, however, the tissue pO2 of the striatum area was significantly higher than in the forelimb area of the cortex. Brain pO2 significantly decreased from the baseline value during 15 min of 15% O2 challenge. No differences in the recovery of the cerebral cortex and striatum pO2 were observed when the rats were allowed to breathe 30% O2. It appears that EPR oximetry using implantable resonators can provide information on pO2 under the experimental conditions needed for such a study. The levels of pO2 that occurred in these experiments are readily resolvable by multi-site EPR oximetry with multi-probe resonators. In addition, the ability to simultaneously measure the pO2 in several areas of the brain provides important information that could potentially help differentiate the pO2 changes that can occur due to global or local mechanisms. PMID:21445770

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

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Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2005-07-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25{+-}2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% {+-} 1.3% and 10.6% {+-} 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% {+-} 4.5% vs. 6.6% {+-} 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release.

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

International Nuclear Information System (INIS)

Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

2005-01-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25±2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% ± 1.3% and 10.6% ± 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% ± 4.5% vs. 6.6% ± 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release

Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

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Atsushi Tamura

Full Text Available The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+ signaling. To characterize Ca(2+ signaling in striatal cells, spontaneous cytoplasmic Ca(2+ transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP in the astrocytes. In both the GFP-negative cells (putative-neurons and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+ transients (referred to as slow Ca(2+ oscillations, which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+ oscillation. Depletion of the intracellular Ca(2+ store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+ oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+ oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+ oscillation in both putative-neurons and astrocytes. The slow Ca(2+ oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+ oscillation may involve in the neuron-glia interaction in the striatum.

Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice

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Muriel Laurent

2017-12-01

Full Text Available The striatum is a key brain structure involved in the processing of cognitive flexibility, which results from the balance between the flexibility demanded for novel learning of motor actions and the inflexibility required to preserve previously learned actions. In particular, the dorsolateral portion of the striatum (DLS is engaged in the learning of action sequence. This process is temporally driven by fine adjustments in the function of the two main neuronal populations of the striatum, known as the direct pathway medium spiny neurons (dMSNs and indirect pathway medium spiny neurons (iMSNs. Here, using optogenetics, behavioral, and electrophysiological tools, we addressed the relative role of both neuronal populations in the acquisition of a reversal dual action sequence in the DLS. While the channelrhodopsin-induced activation of dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the sequence, the specific activation of the dMSNs of the DLS facilitated the acquisition of a reversal dual action sequence; the activation of iMSNs induced a significant deficit in the acquisition of the same task. Taken together our results indicate an antagonistic relationship between dMSNs and iMSNs on the acquisition of a reversal dual action sequence.

Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

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Louise eAdermark

2011-10-01

Full Text Available The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABAA and glycine receptors in regulating synaptic activity in the dorsolateral (DLS and ventral striatum (nucleus accumbens, nAc. Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABAA receptors and strychnine-sensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 µM, inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM and blocked by GABAA receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially sub-region specific manner.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

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Wei Sun

2016-08-01

Full Text Available Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750; COPDGene (N = 590] was used to identify single nucleotide polymorphisms (SNPs associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs. PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs. Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392 explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC. Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER, surfactant protein D (gene = SFTPD, and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis, but distant (trans pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2 for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

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Drummond, M. Bradley; Hawkins, Gregory A.; Yang, Jenny; Chen, Ting-huei; Quibrera, Pedro Miguel; Anderson, Wayne; Barr, R. Graham; Bleecker, Eugene R.; Beaty, Terri; Casaburi, Richard; Castaldi, Peter; Cho, Michael H.; Comellas, Alejandro; Crapo, James D.; Criner, Gerard; Demeo, Dawn; Christenson, Stephanie A.; Couper, David J.; Doerschuk, Claire M.; Freeman, Christine M.; Gouskova, Natalia A.; Han, MeiLan K.; Hanania, Nicola A.; Hansel, Nadia N.; Hersh, Craig P.; Hoffman, Eric A.; Kaner, Robert J.; Kanner, Richard E.; Kleerup, Eric C.; Lutz, Sharon; Martinez, Fernando J.; Meyers, Deborah A.; Peters, Stephen P.; Regan, Elizabeth A.; Rennard, Stephen I.; Scholand, Mary Beth; Silverman, Edwin K.; Woodruff, Prescott G.; O’Neal, Wanda K.; Bowler, Russell P.

2016-01-01

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the

Differences between Neural Activity in Prefrontal Cortex and Striatum during Learning of Novel Abstract Categories

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Antzoulatos, Evan G.; Miller, Earl K.

2011-01-01

Learning to classify diverse experiences into meaningful groups, like categories, is fundamental to normal cognition. To understand its neural basis, we simultaneously recorded from multiple electrodes in the lateral prefrontal cortex and dorsal striatum, two interconnected brain structures critical for learning. Each day, monkeys learned to associate novel, abstract dot-based categories with a right vs. left saccade. Early on, when they could acquire specific stimulus-response associations, ...

Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

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Meng, Chun; Brandl, Felix; Tahmasian, Masoud; Shao, Junming; Manoliu, Andrei; Scherr, Martin; Schwerthöffer, Dirk; Bäuml, Josef; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

2014-02-01

In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter

Comparative study of D2 receptors and content of DA in striatum before and after electro-acupuncture treatment

International Nuclear Information System (INIS)

Lin Yansong; Lin Xiangtong

1999-01-01

Objective: To evaluate the change of D 2 receptors and its relationship with DA content in experimental hemi-parkinsonism rats before and after electron-acupuncture treatment. Methods: 125 I-IBZM D 2 receptor cerebral autoradiographic analysis, HPLC-ECD DA and its metabolites, homovanillic acid (HVA), 3,4-di-hydroxyphenylacetic acid (DOPAC) content detection were used to study in striatum in before treatment, electro-acupuncture treatment and treatment control group. Results: 1) The DA, HVA and DOPAC level in striatum of lesioned side in electro-acupuncture group was increased comparing with the before treatment and treatment control group (P 125 I-IBZM uptake ratio was 8.04 +- 0.71, (29.34 +- 4.83)% more than that of the contralateral side, but no significant difference was observed as compared with that of the pretreatment group [(8.09 +- 0.52), P>0.05]; however it was much lower than that of the treatment control group (8.61 +- 0.63), P 2 receptors' up regulation in rats with experimental hemi-parkinsonism

Induction of Autophagy in the Striatum and Hypothalamus of Mice after 835 MHz Radiofrequency Exposure.

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Ju Hwan Kim

Full Text Available The extensive use of wireless mobile phones and associated communication devices has led to increasing public concern about potential biological health-related effects of the exposure to electromagnetic fields (EMFs. EMFs emitted by a mobile phone have been suggested to influence neuronal functions in the brain and affect behavior. However, the affects and phenotype of EMFs exposure are unclear. We applied radiofrequency (RF of 835 MHz at a specific absorption rate (SAR of 4.0 W/kg for 5 hours/day for 4 and 12 weeks to clarify the biological effects on mouse brain. Interestingly, microarray data indicated that a variety of autophagic related genes showed fold-change within small range after 835 MHz RF exposure. qRT-PCR revealed significant up-regulation of the autophagic genes Atg5, LC3A and LC3B in the striatum and hypothalamus after a 12-week RF. In parallel, protein expression of LC3B-II was also increased in both brain regions. Autophagosomes were observed in the striatum and hypothalamus of RF-exposed mice, based on neuronal transmission electron microscopy. Taken together, the results indicate that RF exposure of the brain can induce autophagy in neuronal tissues, providing insight into the protective mechanism or adaptation to RF stress.

Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats.

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Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan; Lee, Inah

2014-11-19

The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. Copyright © 2014 the authors 0270-6474/14/3415534-14$15.00/0.

Pivotal roles of p53 transcription-dependent and -independent pathways in manganese-induced mitochondrial dysfunction and neuronal apoptosis

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Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Ma, Xa; Shi, Shangshi [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Zhao, Jianya; Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Han, Jingling; Xiao, Jing; Wang, Xiaoke [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Shengyang [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Junkang, E-mail: Jiang_junkang@163.com [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China)

2014-12-15

Chronic exposure to excessive manganese (Mn) has been known to lead to neuronal loss and a clinical syndrome resembling idiopathic Parkinson's disease (IPD). p53 plays an integral role in the development of various human diseases, including neurodegenerative disorders. However, the role of p53 in Mn-induced neuronal apoptosis and neurological deficits remains obscure. In the present study, we showed that p53 was critically involved in Mn-induced neuronal apoptosis in rat striatum through both transcription-dependent and -independent mechanisms. Western blot and immunohistochemistrical analyses revealed that p53 was remarkably upregulated in the striatum of rats following Mn exposure. Coincidentally, increased level of cleaved PARP, a hallmark of apoptosis, was observed. Furthermore, using nerve growth factor (NGF)-differentiated PC12 cells as a neuronal cell model, we showed that Mn exposure decreased cell viability and induced apparent apoptosis. Importantly, p53 was progressively upregulated, and accumulated in both the nucleus and the cytoplasm. The cytoplasmic p53 had a remarkable distribution in mitochondria, suggesting an involvement of p53 mitochondrial translocation in Mn-induced neuronal apoptosis. In addition, Mn-induced impairment of mitochondrial membrane potential (ΔΨm) could be partially rescued by pretreatment with inhibitors of p53 transcriptional activity and p53 mitochondrial translocation, Pifithrin-α (PFT-α) and Pifithrin-μ (PFT-μ), respectively. Moreover, blockage of p53 activities with PFT-α and PFT-μ significantly attenuated Mn-induced reactive oxidative stress (ROS) generation and mitochondrial H{sub 2}O{sub 2} production. Finally, we observed that pretreatment with PFT-α and PFT-μ ameliorated Mn-induced apoptosis in PC12 cells. Collectively, these findings implicate that p53 transcription-dependent and -independent pathways may play crucial roles in the regulation of Mn-induced neuronal death. - Highlights: • p53 is

Pivotal roles of p53 transcription-dependent and -independent pathways in manganese-induced mitochondrial dysfunction and neuronal apoptosis

International Nuclear Information System (INIS)

Wan, Chunhua; Ma, Xa; Shi, Shangshi; Zhao, Jianya; Nie, Xiaoke; Han, Jingling; Xiao, Jing; Wang, Xiaoke; Jiang, Shengyang; Jiang, Junkang

2014-01-01

Chronic exposure to excessive manganese (Mn) has been known to lead to neuronal loss and a clinical syndrome resembling idiopathic Parkinson's disease (IPD). p53 plays an integral role in the development of various human diseases, including neurodegenerative disorders. However, the role of p53 in Mn-induced neuronal apoptosis and neurological deficits remains obscure. In the present study, we showed that p53 was critically involved in Mn-induced neuronal apoptosis in rat striatum through both transcription-dependent and -independent mechanisms. Western blot and immunohistochemistrical analyses revealed that p53 was remarkably upregulated in the striatum of rats following Mn exposure. Coincidentally, increased level of cleaved PARP, a hallmark of apoptosis, was observed. Furthermore, using nerve growth factor (NGF)-differentiated PC12 cells as a neuronal cell model, we showed that Mn exposure decreased cell viability and induced apparent apoptosis. Importantly, p53 was progressively upregulated, and accumulated in both the nucleus and the cytoplasm. The cytoplasmic p53 had a remarkable distribution in mitochondria, suggesting an involvement of p53 mitochondrial translocation in Mn-induced neuronal apoptosis. In addition, Mn-induced impairment of mitochondrial membrane potential (ΔΨm) could be partially rescued by pretreatment with inhibitors of p53 transcriptional activity and p53 mitochondrial translocation, Pifithrin-α (PFT-α) and Pifithrin-μ (PFT-μ), respectively. Moreover, blockage of p53 activities with PFT-α and PFT-μ significantly attenuated Mn-induced reactive oxidative stress (ROS) generation and mitochondrial H 2 O 2 production. Finally, we observed that pretreatment with PFT-α and PFT-μ ameliorated Mn-induced apoptosis in PC12 cells. Collectively, these findings implicate that p53 transcription-dependent and -independent pathways may play crucial roles in the regulation of Mn-induced neuronal death. - Highlights: • p53 is robustly

Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model

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Zheng, Deyu; Jiang, Xiaohua; Zhao, Junpeng; Duan, Deyi; Zhao, Huanying; Xu, Qunyuan

2013-01-01

The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. PMID:23738148

In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning

International Nuclear Information System (INIS)

Gallagher, M.; Bizon, J.L.; Nicolle, M.M.

1996-01-01

Using in vitro autoradiography, we investigated [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [ 3 H]kainate and [ 3 H]N-methyl-d-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [ 3 H]kainate binding in CA3 were reduced. In contrast, N-methyl-d-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [ 3 H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-d-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [ 3 H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-d-aspartate binding in the striatum and [ 3 H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability.Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not neccessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial learning, suggesting a compensatory reduction

Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli

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Lanuza Enrique

2007-11-01

Full Text Available Abstract Background Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae. The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja. Results Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections. Conclusion The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse.

Manganese-induced hydroxyl radical formation in rat striatum is not attenuated by dopamine depletion or iron chelation in vivo

NARCIS (Netherlands)

W.N. Sloot (W.); J. Korf (Jakob); J.F. Koster (Johan); L.E.A. de Wit (Elly); J.-B.P. Gramsbergen (J. B P)

1996-01-01

textabstractThe present studies were aimed at investigating the possible roles of dopamine (DA) and iron in production of hydroxyl radicals (.OH) in rat striatum after Mn2+ intoxication. For this purpose, DA depletions were assessed concomitant with in vivo 2,3- and 2,5-dihydroxybenzoic acid (DHBA)

Striatum-dependent habits are insensitive to both increases and decreases in reinforcer value in mice.

Science.gov (United States)

Quinn, Jennifer J; Pittenger, Christopher; Lee, Anni S; Pierson, Jamie L; Taylor, Jane R

2013-03-01

The mouse has emerged as an advantageous species for studying the brain circuitry that underlies complex behavior and for modeling neuropsychiatric disease. The transition from flexible, goal-directed actions to inflexible, habitual responses is argued to be a valid and reliable behavioral model for studying a core aspect of corticostriatal systems that is implicated in certain forms of psychopathology. This transition is thought to correspond to a progression of behavioral control from associative to sensorimotor corticobasal ganglia networks. Habits form following extensive training and are characterized by reduced sensitivity of instrumental responding to reinforcer revaluation; few studies have examined this form of behavioral control in mice. Here we examined the involvement of the dorsolateral and dorsomedial striatum in this transition in the C57BL/6 inbred mouse strain. We provided evidence that damage to the dorsolateral striatum disrupted habitual responding, i.e. it preserved sensitivity to changes in outcome value following either outcome devaluation or, shown for the first time in mice, outcome inflation. Together, these data show that instrumental responding in lesioned mice tracks the current value of a reinforcer and provide evidence that neuroanatomical mechanisms underlying habit learning in rats are preserved in the mouse. This will allow for the genetic and molecular dissection of neural factors involved in decision-making and mechanisms of aberrant habit formation. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The role of the intrinsic cholinergic system of the striatum: What have we learned from TAN recordings in behaving animals?

Science.gov (United States)

Apicella, Paul

2017-09-30

Cholinergic interneurons provide rich local innervation of the striatum and play an important role in controlling behavior, as evidenced by the variety of movement and psychiatric disorders linked to disrupted striatal cholinergic transmission. Much progress has been made in recent years regarding our understanding of how these interneurons contribute to the processing of information in the striatum. In particular, investigation of the activity of presumed striatal cholinergic interneurons, identified as tonically active neurons or TANs in behaving animals, has pointed to their role in the signaling and learning of the motivational relevance of environmental stimuli. Although the bulk of this work has been conducted in monkeys, several studies have also been carried out in behaving rats, but information remains rather disparate across studies and it is still questionable whether rodent TANs correspond to TANs described in monkeys. Consequently, our current understanding of the function of cholinergic transmission in the striatum is challenged by the rapidly growing, but often confusing literature on the relationship between TAN activity and specific behaviors. As regards the precise nature of the information conveyed by the cholinergic TANs, a recent influential view emphasized that these local circuit neurons may play a special role in the processing of contextual information that is important for reinforcement learning and selection of appropriate actions. This review provides a summary of recent progress in TAN physiology from which it is proposed that striatal cholinergic interneurons are crucial elements for flexible switching of behaviors under changing environmental conditions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Comparative Analysis of Root Traits and the Associated QTLs for Maize Seedlings Grown in Paper Roll, Hydroponics and Vermiculite Culture System.

Science.gov (United States)

Liu, Zhigang; Gao, Kun; Shan, Shengchen; Gu, Riling; Wang, Zhangkui; Craft, Eric J; Mi, Guohua; Yuan, Lixing; Chen, Fanjun

2017-01-01

Root system architecture (RSA) plays an important role in the acquisition of both nitrogen (N) and phosphorus (P) from the environment. Currently RSA is rarely considered as criteria for selection to improve nutrient uptake efficiency in crop breeding. Under field conditions roots can be greatly influenced by uncontrolled environment factors. Therefore, it is necessary to develop fast selection methods for evaluating root traits of young seedlings in the lab which can then be related to high nutrient efficiency of adult plants in the field. Here, a maize recombination inbred line (RILs) population was used to compare the genetic relationship between RSA and nitrogen and phosphorous efficiency traits. The phenotypes of eight RSA-related traits were evaluated in young seedlings using three different growth systems (i.e., paper roll, hydroponics and vermiculite), and then subjected to correlation analysis with N efficiency and P efficiency related traits measured under field conditions. Quantitative trait loci (QTL) of RSA were determined and QTL co-localizations across different growth systems were further analyzed. Phenotypic associations were observed for most of RSA traits among all three culture systems. RSA-related traits in hydroponics and vermiculite weakly correlated with Nitrogen (NupE) uptake efficiency ( r = 0.17-0.31) and Phosphorus (PupE) uptake efficiency ( r = 0.22-0.34). This correlation was not found in the paper roll growth system. A total of 14 QTLs for RSA were identified in paper rolls, 18 in hydroponics, and 14 in vermiculite. Co-localization of QTLs for RSA traits were identified in six chromosome regions of bin 1.04/1.05, 1.06, 2.04/2.05, 3.04, 4.05, and 5.04/5.05. The results suggest the problem of using the phenotype from one growth system to predict those in another growth system. Assessing RSA traits at the seedling stage using either hydroponics or a vermiculite system appears better suited than the paper roll system as an important index

Learning multiple variable-speed sequences in striatum via cortical tutoring.

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Murray, James M; Escola, G Sean

2017-05-08

Sparse, sequential patterns of neural activity have been observed in numerous brain areas during timekeeping and motor sequence tasks. Inspired by such observations, we construct a model of the striatum, an all-inhibitory circuit where sequential activity patterns are prominent, addressing the following key challenges: (i) obtaining control over temporal rescaling of the sequence speed, with the ability to generalize to new speeds; (ii) facilitating flexible expression of distinct sequences via selective activation, concatenation, and recycling of specific subsequences; and (iii) enabling the biologically plausible learning of sequences, consistent with the decoupling of learning and execution suggested by lesion studies showing that cortical circuits are necessary for learning, but that subcortical circuits are sufficient to drive learned behaviors. The same mechanisms that we describe can also be applied to circuits with both excitatory and inhibitory populations, and hence may underlie general features of sequential neural activity pattern generation in the brain.

Distinct cellular and subcellular distributions of G protein-coupled receptor kinase and arrestin isoforms in the striatum.

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Evgeny Bychkov

Full Text Available G protein-coupled receptor kinases (GRKs and arrestins mediate desensitization of G protein-coupled receptors (GPCR. Arrestins also mediate G protein-independent signaling via GPCRs. Since GRK and arrestins demonstrate no strict receptor specificity, their functions in the brain may depend on their cellular complement, expression level, and subcellular targeting. However, cellular expression and subcellular distribution of GRKs and arrestins in the brain is largely unknown. We show that GRK isoforms GRK2 and GRK5 are similarly expressed in direct and indirect pathway neurons in the rat striatum. Arrestin-2 and arrestin-3 are also expressed in neurons of both pathways. Cholinergic interneurons are enriched in GRK2, arrestin-3, and GRK5. Parvalbumin-positive interneurons express more of GRK2 and less of arrestin-2 than medium spiny neurons. The GRK5 subcellular distribution in the human striatal neurons is altered by its phosphorylation: unphosphorylated enzyme preferentially localizes to synaptic membranes, whereas phosphorylated GRK5 is found in plasma membrane and cytosolic fractions. Both GRK isoforms are abundant in the nucleus of human striatal neurons, whereas the proportion of both arrestins in the nucleus was equally low. However, overall higher expression of arrestin-2 yields high enough concentration in the nucleus to mediate nuclear functions. These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling.

5-HMF attenuates striatum oxidative damage via Nrf2/ARE signaling pathway following transient global cerebral ischemia.

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Ya, Bai-Liu; Li, Hong-Fang; Wang, Hai-Ying; Wu, Fei; Xin, Qing; Cheng, Hong-Ju; Li, Wen-Juan; Lin, Na; Ba, Zai-Hua; Zhang, Ru-Juan; Liu, Qian; Li, Ya-Nan; Bai, Bo; Ge, Feng

2017-01-01

Recent studies have shown 5-hydroxymethyl-2-furfural (5-HMF) has favorable biological effects, and its neuroprotection in a variety of neurological diseases has been noted. Our previous study showed that treatment of 5-HMF led to protection against permanent global cerebral ischemia. However, the underlying mechanisms in cerebral ischemic injury are not fully understood. This study was conducted to investigate the neuroprotective effect of 5-HMF and elucidate the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway mechanism in the striatum after transient global cerebral ischemia. C57BL/6 mice were subjected to bilateral common carotid artery occlusion for 20 min and sacrificed 24 h after reperfusion. 5-HMF (12 mg/kg) or an equal volume of vehicle was intraperitoneally injected 30 min before ischemia and 5 min after the onset of reperfusion. At 24 h after reperfusion, neurological function was evaluated by neurological disability status scale, locomotor activity test and inclined beam walking test. Histological injury of the striatum was observed by cresyl violet staining and terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) staining. Oxidative stress was evaluated by the carbonyl groups introduced into proteins, and malondialdehyde (MDA) levels. An enzyme-linked immunosorbent assay (ELISA)-based measurement was used to detect Nrf2 DNA binding activity. Nrf2 and its downstream ARE pathway protein expression such as heme oxygenase-1, NAD (P)H:quinone oxidoreductase 1, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modulatory subunit were detected by western blot. Our results showed that 5-HMF treatment significantly ameliorated neurological deficits, reduced brain water content, attenuated striatum neuronal damage, decreased the carbonyl groups and MDA levels, and activated Nrf2/ARE signaling pathway. Taken together, these results demonstrated that

Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lypopolysaccharide in the hippocampus and striatum of male mice

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Astiz, Mariana, E-mail: marianaastiz@gmail.com; Diz-Chaves, Yolanda, E-mail: ydiz@cajal.csic.es; Garcia-Segura, Luis M., E-mail: lmgs@cajal.csic.es

2013-10-15

Dimethoate is an organophosphorus insecticide extensively used in horticulture. Previous studies have shown that the administration of dimethoate to male rats, at a very low dose and during a sub-chronic period, increases the oxidation of lipids and proteins, reduces the levels of antioxidants and impairs mitochondrial function in various brain regions. In this study, we have assessed in C57Bl/6 adult male mice, whether sub-chronic (5 weeks) intoxication with a low dose of dimethoate (1.4 mg/kg) affects the expression of inflammatory molecules and the reactivity of microglia in the hippocampus and striatum under basal conditions and after an immune challenge caused by the systemic administration of lipopolysaccharide. Dimethoate increased mRNA levels of tumor necrosis factor α (TNFα) and interleukin (IL) 6 in the hippocampus, and increased the proportion of Iba1 immunoreactive cells with reactive phenotype in dentate gyrus and striatum. Lipopolysaccharide caused a significant increase in the mRNA levels of IL1β, TNFα, IL6 and interferon-γ-inducible protein 10, and a significant increase in the proportion of microglia with reactive phenotype in the hippocampus and the striatum. Some of the effects of lipopolysaccharide (proportion of Iba1 immunoreactive cells with reactive phenotype and IL6 mRNA levels) were amplified in the animals treated with dimethoate, but only in the striatum. These findings indicate that a sub-chronic period of administration of a low dose of dimethoate, comparable to the levels of the pesticide present as residues in food, causes a proinflammatory status in the brain and enhances the neuroinflammatory response to the lipopolysaccharide challenge with regional specificity. - Highlights: • The dose of pesticide used was comparable to the levels of residues found in food. • Dimethoate administration increased cytokine expression and microglia reactivity. • Hippocampus and striatum were differentially affected by the treatment. �

Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

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Matthijs A A Van Der Meer

2009-06-01

Full Text Available Local field potential (LFP oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson’s disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45-55 Hz and gamma-80 (70-85 Hz oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

Sexual dimorphism in song-induced ZENK expression in the medial striatum of juvenile zebra finches

OpenAIRE

Bailey, David J.; Wade, Juli

2006-01-01

In the brains of male zebra finches (Taeniopygia guttata), the nuclei that direct song learning and production are larger than the corresponding regions in females, who do not sing. The dimorphism in Area X of the medial striatum (MSt), an area important for song learning, is even more dramatic in that it is identifiable in males but not females by Nissl stain. In the present study, conspecific song, but not other auditory stimuli, induced expression of the immediate early gene ZENK in the MS...

Release of /sup 3/H-. cap alpha. -methyl-m-tyramine from rat striatum in vitro

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Dorris, R L [Baylor College of Dentistry, Dallas, Tex. (USA). Dept. of Pharmacology

1976-01-01

Release of /sup 3/H-d-..cap alpha..-methyl-m-tyramine (/sup 3/H-MMTA), a false dopaminergic transmitter from rat striatum was studied in vitro. After its initial uptake, /sup 3/H-MMTA was released by high K/sup +/ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that /sup 3/H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.

Time-dependent effects of repeated THC treatment on dopamine D2/3 receptor-mediated signalling in midbrain and striatum.

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Tournier, Benjamin B; Tsartsalis, Stergios; Dimiziani, Andrea; Millet, Philippe; Ginovart, Nathalie

2016-09-15

This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D2/3R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D2/3R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D2/3R function and a decreased DA presynaptic signaling, mediated by increased D2/3R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D2/3R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum.

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Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

2018-04-01

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

The brain cytoplasmic RNA BC1 regulates dopamine D-2 receptor-mediated transmission in the striatum

OpenAIRE

Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

2007-01-01

Dopamine D-2 receptor (D2DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D-2 receptors in this brain area are essentially obscure. We have studied the physiological responses of the D2DR stimulations in mice...

Study on microstructure of corpus striatum in patients with idiopathic rapid eye movement sleep behavior disorder using magnetic resonance imaging

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Ya-meng ZHANG

2017-07-01

Full Text Available Objective To investigate the structure of corpus striatum and the integrity of white matter fiber in patients with Parkinson's disease (PD and idiopathic rapid eye movement sleep behavior disorder (iRBD.  Methods Twelve patients with iRBD, 12 patients with PD and 10 healthy subjects that were well matched in gender, age and education were enrolled in this study. Head MRI examination was performed to all subjects to observe the changes of corpus striatum structure (the gray matter volume and the integrity of white matter fiber [fractional anisotropy (FA] by combining voxel?based morphometry (VBM and diffusion tensor imaging (DTI.  Results Compared with healthy subjects, the gray matter volume of left caudate nucleus was significantly decreased (P < 0.005, and FA values of left caudate nucleus (P < 0.005, right caudate nucleus (P < 0.001 and right putamen (P < 0.05 were all significantly reduced in iRBD patients; FA value of right putamen was significantly decreased in PD patients (P < 0.05. Compared with PD patients, the gray matter volume of left caudate nucleus of iRBD patients was significantly reduced (P < 0.001, FA values of left caudate nucleus (P < 0.01 and right caudate nucleus (P < 0.005 of iRBD patients were significantly reduced.  Conclusions There is atrophy of gray matter volume and extensive white matter fiber impairment in corpus striatum of patients with iRBD, and the white matter fiber impairment was similar to PD, which provides an anatomical evidence for iRBD being presymptom of PD. DOI: 10.3969/j.issn.1672-6731.2017.05.008

Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum.

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Jupp, Bianca; Murray, Jennifer E; Jordan, Emily R; Xia, Jing; Fluharty, Meg; Shrestha, Saurav; Robbins, Trevor W; Dalley, Jeffrey W

2016-02-01

Studies in human and non-human primates demonstrate that social status is an important determinant of cocaine reinforcement. However, it is unclear whether social rank is associated with other traits that also predispose to addiction and whether social status similarly predicts cocaine self-administration in rats. The objective of this study is to investigate whether social ranking assessed using a resource competition task affects (i) the acquisition, maintenance and reinstatement of cocaine self-administration; (ii) the dopaminergic markers in the striatum; and (iii) the expression of ancillary traits for addiction. Social ranking was determined in group-housed rats based upon drinking times during competition for a highly palatable liquid. Rats were then evaluated for cocaine self-administration and cue-induced drug reinstatement or individual levels of impulsivity, anxiety and novelty-induced locomotor activity. Finally, dopamine content, dopamine transporter (DAT) and dopamine D2/D3 (D2/3) receptor binding were measured postmortem in the dorsal and ventral striatum. Rats deemed socially dominant showed enhanced novelty reactivity but were neither more impulsive nor anxious compared with subordinate rats. Dominant rats additionally maintained higher rates of cocaine self-administration but showed no differences in the acquisition, extinction and reinstatement of this behaviour. D2/3 binding was elevated in the nucleus accumbens shell and dorsal striatum of dominant rats when compared to subordinate rats, and was accompanied by elevated DAT and reduced dopamine content in the nucleus accumbens shell. These findings show that social hierarchy influences the rate of self-administered cocaine but not anxiety or impulsivity in rats. Similar to non-human primates, these effects may be mediated by striatal dopaminergic systems.

The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

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Todd M. Mowery

2017-06-01

Full Text Available Corticostriatal circuits play a fundamental role in regulating many behaviors, and their dysfunction is associated with many neurological disorders. In contrast, sensory disorders, like hearing loss (HL, are commonly linked with processing deficits at or below the level of the auditory cortex (ACx. However, HL can be accompanied by non-sensory deficits, such as learning delays, suggesting the involvement of regions downstream of ACx. Here, we show that transient developmental HL differentially affected the ACx and its downstream target, the sensory striatum. Following HL, both juvenile ACx layer 5 and striatal neurons displayed an excitatory-inhibitory imbalance and lower firing rates. After hearing was restored, adult ACx neurons recovered balanced excitatory-inhibitory synaptic gain and control-like firing rates, but striatal neuron synapses and firing properties did not recover. Thus, a brief period of abnormal cortical activity may induce cellular impairments that persist into adulthood and contribute to neurological disorders that are striatal in origin.

Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum.

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de Oliveira, Iris Machado; Nunes, Brenda Viviane Ferreira; Barbosa, Durán Rafael; Pallares, Alfonso Miguel; Faro, Lilian Rosana Ferreira

2010-02-15

Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC. Intrastriatal administration of 1mM or 5mM TMX has not produced significant increases on dopamine (DA) levels, nonetheless the infusion of 10mM TMX increases the DA output to 841+/-132%, when compared to basal levels. Infusion of 1mM CLO has not induced a significant increase in DA levels, even so 2, 3.5 and 5mM CLO have produced an increase of 438+/-8%, 2778+/-598% and 4604+/-516%, respectively, every compared to basal levels. Mecamylamine (MEC), a non-competitive nAChRs antagonist, was used to investigate the role of nAChRs on DA release induced by TMX and CLO. The increases in extracellular DA levels induced by TMX and CLO when associated to MEC are 80% and 68% lower than the effect produced by CLO and TMX isolated. These results confirm that TMX and CLO appear to induce in vivo DA increased release in striatum of rats and it seems to be concentration dependent. Moreover, these results indicate that this effect might be related to nAChRs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

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John M Burkhardt

2009-10-01

Full Text Available Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson’s disease.

Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice.

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Kozuka, Chisayo; Kaname, Tadashi; Shimizu-Okabe, Chigusa; Takayama, Chitoshi; Tsutsui, Masato; Matsushita, Masayuki; Abe, Keiko; Masuzaki, Hiroaki

2017-08-01

Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control. We therefore explored the possibility that γ-oryzanol would modulate functioning of the brain reward system in mice. Male C57BL/6J mice fed an HFD were orally treated with γ-oryzanol, and striatal levels of molecules involved in D2R signalling were evaluated. The impact of γ-oryzanol on DNA methylation of the D2R promoter and subsequent changes in preferences for dietary fat was examined. In addition, the effects of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA methyltransferases (DNMTs), on food preference, D2R signalling and the levels of DNMTs in the striatum were investigated. The inhibitory effects of γ-oryzanol on the activity of DNMTs were enzymatically evaluated in vitro. In striatum from mice fed an HFD, the production of D2Rs was decreased via an increase in DNA methylation of the promoter region of the D2R. Oral administration of γ-oryzanol decreased the expression and activity of DNMTs, thereby restoring the level of D2Rs in the striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated the preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in the striatum of mice. Our experimental paradigm highlights �

Identification of female-specific QTLs affecting an emotionality-related behavior in rats.

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Ramos, A; Moisan, M P; Chaouloff, F; Mormède, C; Mormède, P

1999-09-01

The influence of genetic factors on psychological traits and disorders has been repeatedly demonstrated; however, the molecular mechanisms underlying such an influence remain largely unknown. Anxiety-related disorders constitute the most common class of mental disorder in humans, with women being diagnosed far more frequently than men. A better understanding of the genetic and gender-related mechanisms mediating anxiety traits should enable the development of more rational methods for preventing and treating anxiety disorders. In this study we have aimed to identify, for the first time, quantitative trait loci (QTL) influencing anxiety/emotionality-related traits in rats. To this end, two strains-Lewis (LEW) and Spontaneously Hypertensive Rats (SHR)-that differ for several behavioral measures of anxiety/emotionality were intercrossed. A QTL analysis of the F2 population revealed suggestive loci for various traits, including behaviors in the elevated plus-maze and blood pressure. In addition, one major QTL explaining 50.4% of the total variance (LOD = 7.22) was identified on chromosome 4 for the locomotion in the central and aversive area of the open field. Two other relevant QTLs have been recently mapped near this chromosomic region in the rat, which also harbors Tac1r, the gene encoding for the substance P receptor. Our major QTL affected females but not males and its effect depended on the type of cross (LEW or SHR grandmothers). The present results reveal a complex genetic basis underlying emotional behaviors and they confirm the existence of interactions between genetic factors and sex for this kind of trait. Further investigation of the loci identified herein may give clues to the pathophysiology of psychiatric disorders such as anxiety-related ones.

Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

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Sumiya, Motofumi; Koike, Takahiko; Okazaki, Shuntaro; Kitada, Ryo; Sadato, Norihiro

2017-10-01

Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum, measured using in vivo microdialysis and PET

International Nuclear Information System (INIS)

Opacka-Juffry, J.; Hume, S. P.; Ashworth, S.; Ahier, R. G.

1997-01-01

Putative modulatory effects of L-3,4-dihydroxyphenylalanine (L-DOPA) on D2 dopamine receptor function in the striatum of anaesthetized rats were investigated using both in vivo microdialysis and positron emission tomography (PET) with carbon-11 labelled raclopride as a selective D2 receptor ligand. A single dose of L-DOPA (20 or 100 mg/kg i.p.) resulted in an increase in [ 11 C]raclopride binding potential which was also observed in the presence of the central aromatic decarboxylase inhibitor NSD 1015, confirming that the effect was independent of dopamine. This L-DOPA evoked D2 receptor sensitization was abolished by a prior, long-term administration of L-DOPA in drinking water (5 weeks, 170 mg/kg/day). In the course of acute L-DOPA treatment (20 mg/kg), extracellular GABA levels were reduced by ∼20 % in the globus pallidus. It is likely that L-DOPA sensitising effect on striatal D2 receptors, as confirmed by PET, may implicate striato-pallidal neurones, hence a reduced GABA-ergic output in the projection area. Since the L-DOPA evoked striatal D2 receptor supersensitivity habituates during long-term treatment, the effects reported here may contribute to the fluctuations observed during chronic L-DOPA therapy in Parkinson's disease. (author)

QTL detection for wheat kernel size and quality and the responses of these traits to low nitrogen stress.

Science.gov (United States)

Cui, Fa; Fan, Xiaoli; Chen, Mei; Zhang, Na; Zhao, Chunhua; Zhang, Wei; Han, Jie; Ji, Jun; Zhao, Xueqiang; Yang, Lijuan; Zhao, Zongwu; Tong, Yiping; Wang, Tao; Li, Junming

2016-03-01

QTLs for kernel characteristics and tolerance to N stress were identified, and the functions of ten known genes with regard to these traits were specified. Kernel size and quality characteristics in wheat (Triticum aestivum L.) ultimately determine the end use of the grain and affect its commodity price, both of which are influenced by the application of nitrogen (N) fertilizer. This study characterized quantitative trait loci (QTLs) for kernel size and quality and examined the responses of these traits to low-N stress using a recombinant inbred line population derived from Kenong 9204 × Jing 411. Phenotypic analyses were conducted in five trials that each included low- and high-N treatments. We identified 109 putative additive QTLs for 11 kernel size and quality characteristics and 49 QTLs for tolerance to N stress, 27 and 14 of which were stable across the tested environments, respectively. These QTLs were distributed across all wheat chromosomes except for chromosomes 3A, 4D, 6D, and 7B. Eleven QTL clusters that simultaneously affected kernel size- and quality-related traits were identified. At nine locations, 25 of the 49 QTLs for N deficiency tolerance coincided with the QTLs for kernel characteristics, indicating their genetic independence. The feasibility of indirect selection of a superior genotype for kernel size and quality under high-N conditions in breeding programs designed for a lower input management system are discussed. In addition, we specified the functions of Glu-A1, Glu-B1, Glu-A3, Glu-B3, TaCwi-A1, TaSus2, TaGS2-D1, PPO-D1, Rht-B1, and Ha with regard to kernel characteristics and the sensitivities of these characteristics to N stress. This study provides useful information for the genetic improvement of wheat kernel size, quality, and resistance to N stress.

Genome-wide Analysis of RARβ Transcriptional Targets in Mouse Striatum Links Retinoic Acid Signaling with Huntington's Disease and Other Neurodegenerative Disorders.

Science.gov (United States)

Niewiadomska-Cimicka, Anna; Krzyżosiak, Agnieszka; Ye, Tao; Podleśny-Drabiniok, Anna; Dembélé, Doulaye; Dollé, Pascal; Krężel, Wojciech

2017-07-01

Retinoic acid (RA) signaling through retinoic acid receptors (RARs), known for its multiple developmental functions, emerged more recently as an important regulator of adult brain physiology. How RAR-mediated regulation is achieved is poorly known, partly due to the paucity of information on critical target genes in the brain. Also, it is not clear how reduced RA signaling may contribute to pathophysiology of diverse neuropsychiatric disorders. We report the first genome-wide analysis of RAR transcriptional targets in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis of RARβ-null mutant mice, we identified genomic targets of RARβ in the striatum. Characterization of RARβ transcriptional targets in the mouse striatum points to mechanisms through which RAR may control brain functions and display neuroprotective activity. Namely, our data indicate with statistical significance (FDR 0.1) a strong contribution of RARβ in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein coupled receptor (p = 5.0e -5 ), cAMP (p = 4.5e -4 ), and calcium signaling (p = 3.4e -3 ). Many identified RARβ target genes related to these pathways have been implicated in Alzheimer's, Parkinson's, and Huntington's disease (HD), raising the possibility that compromised RA signaling in the striatum may be a mechanistic link explaining the similar affective and cognitive symptoms in these diseases. The RARβ transcriptional targets were particularly enriched for transcripts affected in HD. Using the R6/2 transgenic mouse model of HD, we show that partial sequestration of RARβ in huntingtin protein aggregates may account for reduced RA signaling reported in HD.

c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats.

Science.gov (United States)

Dela Cruz, J A D; Coke, T; Karagiorgis, T; Sampson, C; Icaza-Cukali, D; Kest, K; Ranaldi, R; Bodnar, R J

2015-02-01

Overconsumption of nutrients high in fats and sugars can lead to obesity. Previous studies indicate that sugar or fat consumption activate individual brain sites using Fos-like immunoreactivity (FLI). Sugars and fats also elicit conditioned flavor preferences (CFP) that are differentially mediated by flavor-flavor (orosensory: f/f) and flavor-nutrient (post-ingestive: f/n) processes. Dopamine (DA) signaling in the medial prefrontal cortex (mPFC), the amygdala (AMY) and the nucleus accumbens (NAc), has been implicated in acquisition and expression of fat- and sugar-CFP. The present study examined the effects of acute consumption of fat (corn oil: f/f and f/n), glucose (f/f and f/n), fructose, (f/f only), saccharin, xanthan gum or water upon simultaneous FLI activation of DA mesotelencephalic nuclei (ventral tegmental area (VTA)) and projections (infralimbic and prelimbic mPFC, basolateral and central-cortico-medial AMY, core and shell of NAc as well as the dorsal striatum). Consumption of corn oil solutions, isocaloric to glucose and fructose, significantly increased FLI in all sites except for the NAc shell. Glucose intake significantly increased FLI in both AMY areas, dorsal striatum and NAc core, but not in either mPFC area, VTA or Nac shell. Correspondingly, fructose intake significantly increased FLI in the both AMY areas, the infralimbic mPFC and dorsal striatum, but not the prelimbic mPFC, VTA or either NAc area. Saccharin and xanthan gum intake failed to activate FLI relative to water. When significant FLI activation occurred, highly positive relationships were observed among sites, supporting the idea of activation of a distributed brain network mediating sugar and fat intake. Copyright © 2014 Elsevier Inc. All rights reserved.

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

International Nuclear Information System (INIS)

Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

2012-01-01

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and ( 11 C)raclopride (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D 2 /D 3 receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

Energy Technology Data Exchange (ETDEWEB)

Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

2012-01-18

Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [{sup 11}C]raclopride (D{sub 2}/D{sub 3} receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D{sub 2}/D{sub 3} receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

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Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

2014-03-01

We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

Correlation between (3H)dopamine specific uptake and (3H)GBR 12783 specific binding during the maturation of rat striatum

International Nuclear Information System (INIS)

Bonnet, J.J.; Costentin, J.

1989-01-01

The development of the specific uptake of dopamine in the rat striatum during the early postnatal period is compared with the ontogenetic changes of the specific binding of ( 3 H)GBR 12783 to the site of uptake inhibition. During maturation, the increase in the specific binding of ( 3 H)GBR 12783 parallels the increase in the specific uptake of dopamine. ( 3 H)GBR 12783 specific binding sites increase in number from day 1 postpartum until 40 days, when they reach the adult level. In 40 day-old rats, the weight of the striatum represents 80% of adult values. The affinity of ( 3 H)GBR 12783 for the inhibition site is similar in membrane preparations obtained from 6 day-old pups and adults; this results in a same ability of the inhibitor to block the specific uptake of dopamine into synaptosomes obtained from pups or adult rats. These data support the hypothesis of the existence of a single molecular entity including both the inhibition site and the carrier itself

Being in a romantic relationship is associated with reduced gray matter density in striatum and increased subjective happiness

OpenAIRE

Hiroaki Kawamichi; Hiroaki Kawamichi; Hiroaki Kawamichi; Sho K Sugawara; Yuki H Hamano; Yuki H Hamano; Kai Makita; Masahiro Matsunaga; Hiroki C Tanabe; Yuichi Ogino; Shigeru Saito; Norihiro Sadato; Norihiro Sadato

2016-01-01

Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness

OpenAIRE

Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Matsunaga, Masahiro; Tanabe, Hiroki C.; Ogino, Yuichi; Saito, Shigeru; Sadato, Norihiro

2016-01-01

Romantic relationship, a widespread feature of human society, is one of the most influential factors in daily life. Although stimuli related to romantic love or being in a romantic relationship commonly result in enhancement of activation or functional connectivity of the reward system, including the striatum, the structure underlying romantic relationship-related regions remain unclear. Because individual experiences can alter gray matter within the adult human brain, we hypothesized that ro...

Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial Striatum in Incubation of Methamphetamine Craving.

Science.gov (United States)

Li, Xuan; Witonsky, Kailyn R; Lofaro, Olivia M; Surjono, Felicia; Zhang, Jianjun; Bossert, Jennifer M; Shaham, Yavin

2018-02-28

Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into the DMS and local D1R-glutamate interaction in this incubation in male rats. We first measured projection-specific activation on day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity marker) double-labeling in projection areas. Next, we determined the effect of pharmacological reversible inactivation of lateral or medial anterior intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on withdrawal day 30. We then used an anatomical asymmetrical disconnection procedure to determine whether an interaction between AIT-L→DMS glutamatergic projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We also determined the effect of unilateral inactivation of AIT-L and D1R blockade of DMS on incubated Meth seeking, and the effect of contralateral disconnection of AIT-L→DMS projections on nonincubated Meth seeking on withdrawal day 1. Incubated Meth seeking was associated with selective activation of AIT→DMS projections; other glutamatergic projections to DMS were not activated. AIT-L (but not AIT-M) inactivation or anatomical disconnection of AIT-L→DMS projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or D1R blockade of the DMS had no effect on incubated Meth craving, and contralateral disconnection of AIT-L→DMS projections had no effect on nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L→DMS glutamatergic projections in incubation of drug craving and drug seeking. SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases after withdrawal from drug self-administration, a phenomenon termed incubation of

Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain.

Science.gov (United States)

Pan, Weixing X; Mao, Tianyi; Dudman, Joshua T

2010-01-01

The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

Differential sensitivity of tachykinin vs. enkephalin gene expression in the posterior striatum in response to acute p-chloroamphetamine treatment during postnatal development.

Science.gov (United States)

Basura, G J; Walker, P D

1999-01-11

The acute effects of the monoamine releaser p-chloroamphetamine (pCA, 10 mg/kg, i.p.) on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the anterior (A-STR) vs. posterior (P-STR) striatum were studied in rodents at postnatal days (PND) 10, 21 and 35. Northern analysis 4 h post-injection yielded no significant mRNA changes within the A-STR of any pCA group. However, significant increases (80-200% of saline control) in PPT mRNA levels occurred within the P-STR at all three postnatal ages. Interestingly, pCA did not increase PPE mRNA levels within the P-STR until PND 35 (150% of saline control). Such observation suggests that tachykinin neurons of the P-STR achieve an earlier monoamine-responsive signal transduction linkage to gene regulation as compared to enkephalin neurons. Given its predominance in the caudal regions of the striatum, 5-HT neurotransmission at the 5-HT2 receptor is suggested to play a central role in this mechanism.

Dorsolateral Striatum Engagement Interferes with Early Discrimination Learning

Directory of Open Access Journals (Sweden)

Hadley C. Bergstrom

2018-05-01

Full Text Available Summary: In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning. : What is the contribution of the DLS in early discrimination learning? Bergstrom et al. show using in vivo optogenetics, fluorescence in situ hybridization, and brain-wide activity mapping that silencing the DLS facilitates early discrimination learning, drives activity in a parallel PL-DMS circuit, and preferentially recruits the DLS “direct” output pathway. Keywords: striatum, reward, goal-directed, habit, optogenetics, plasticity, cognition, Arc

The Dopamine D2 Receptor Gene in Lamprey, Its Expression in the Striatum and Cellular Effects of D2 Receptor Activation

Science.gov (United States)

Robertson, Brita; Huerta-Ocampo, Icnelia; Ericsson, Jesper; Stephenson-Jones, Marcus; Pérez-Fernández, Juan; Bolam, J. Paul; Diaz-Heijtz, Rochellys; Grillner, Sten

2012-01-01

All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates. PMID:22563388

The effect of crack cocaine addiction on the microstructure and morphology of the human striatum and thalamus using novel shape analysis and fast diffusion kurtosis imaging

DEFF Research Database (Denmark)

Garza-Villarreal, Eduardo A.; Mallar, Chakravarty; Hansen, Brian

2016-01-01

The striatum and thalamus are subcortical structures intimately involved in addiction, and the morphology and microstructure of these has been studied in murine models of cocaine addiction. However, human studies using non-invasive MRI has shown inconsistencies in morphology using volumetric...... analysis. In our study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC). We did not find....... Our findings suggest that the use of finer methods and sequences is needed to characterize morphological and microstructural changes in cocaine addiction, and that brain changes in cocaine addiction are related to age....

The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

Science.gov (United States)

Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

2016-01-01

Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

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Piechota Marcin

2006-06-01

Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

Regulation of Pleiotrophin and Fyn in the striatum of rats undergoing L-DOPA-induced dyskinesia.

Science.gov (United States)

Gomez, Gimena; Saborido, Mariano D; Bernardi, M Alejandra; Gershanik, Oscar S; Taravini, Irene R; Ferrario, Juan E

2018-02-14

L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats. We have also shown that both mRNA and protein levels of RPTPζ/β, a PTN receptor, were upregulated in the same experimental condition and expressed in striatal medium spiny neurons. The PTN-RPTPζ/β intracellular pathway has not been fully explored and it might be implicated in the striatal plastic changes triggered by L-DOPA treatment. RPTPζ/β is part of the postsynaptic density zone and modulates Fyn, a Src tyrosine kinase that regulates the NR2A and NR2B subunits of the NMDA receptor and has been singled out as a key molecule in the development of LID. In this study, we evaluated the changes in PTN and Fyn protein levels and Fyn phosphorylation status in the 6-OHDA rat model of PD rendered dyskinetic with L-DOPA. We found an increase in the number of PTN immunoreactive neurons, no changes in the amount of total Fyn but a significant increase in Fyn phosphorylation in the dorsolateral striatum of dyskinetic rats. Our results support the idea that both PTN and Fyn may be involved in the development of LID, further contributing to the understanding of its molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

Science.gov (United States)

Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

2017-06-01

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

International Nuclear Information System (INIS)

Hennies, H.H.; Hess, V.; Flohe, L.

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

Inputs to the dorsal striatum of the mouse conserve the parallel circuit architecture of the forebrain

Directory of Open Access Journals (Sweden)

Weixing X Pan

2010-12-01

Full Text Available The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing number of mouse lines allow extensive identification, characterization, and, manipulation of specified cell types in the basal ganglia. Despite the promise of genetically modified mice for elucidating the functional roles of diverse cell types, there is relatively little anatomical data obtained directly in the mouse. Here we have characterized the retrograde labeling obtained from a series of tracer injections throughout the dorsal striatum of adult mice. We found systematic variations in input along both the medial-lateral and anterior-posterior neuraxes in close agreement with canonical features of basal ganglia anatomy in the rat. In addition to the canonical features we have provided experimental support for the importance of non-canonical inputs to the striatum from the raphe nuclei and the amygdala. To look for organization at a finer scale we have analyzed the correlation structure of labeling intensity across our entire dataset. Using this analysis we found substantial local heterogeneity within the large-scale order. From this analysis we conclude that individual striatal sites receive varied combinations of cortical and thalamic input from multiple functional areas, consistent with some earlier studies in the rat that have suggested the presence of a combinatorial map.

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

Science.gov (United States)

Sagredo, Onintza; González, Sara; Aroyo, Ilia; Pazos, María Ruth; Benito, Cristina; Lastres-Becker, Isabel; Romero, Juan P.; Tolón, Rosa M.; Mechoulam, Raphael; Brouillet, Emmanuel; Romero, Julián; Fernández-Ruiz, Javier

2009-01-01

Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington’s disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be up-regulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. PMID:19115380

Mechanisms of Neuroplasticity and Ethanol’s Effects on Plasticity in the Striatum and Bed Nucleus of the Stria Terminalis

Science.gov (United States)

Lovinger, David M.; Kash, Thomas L.

2015-01-01

Long-lasting changes in synaptic function (i.e., synaptic plasticity) have long been thought to contribute to information storage in the nervous system. Although synaptic plasticity mainly has adaptive functions that allow the organism to function in complex environments, it is now clear that certain events or exposure to various substances can produce plasticity that has negative consequences for organisms. Exposure to drugs of abuse, in particular ethanol, is a life experience that can activate or alter synaptic plasticity, often resulting in increased drug seeking and taking and in many cases addiction. Two brain regions subject to alcohol’s effects on synaptic plasticity are the striatum and bed nucleus of the stria terminalis (BNST), both of which have key roles in alcohol’s actions and control of intake. The specific effects depend on both the brain region analyzed (e.g., specific subregions of the striatum and BNST) and the duration of ethanol exposure (i.e., acute vs. chronic). Plastic changes in synaptic transmission in these two brain regions following prolonged ethanol exposure are thought to contribute to excessive alcohol drinking and relapse to drinking. Understanding the mechanisms underlying this plasticity may lead to new therapies for treatment of these and other aspects of alcohol use disorder. PMID:26259092

Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits

OpenAIRE

Mowery, Todd M.; Harrold, Jon B.; Alloway, Kevin D.

2011-01-01

The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neur...

Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

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Maxime Rotival

2011-12-01

Full Text Available One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739, previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1 is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178, which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644 was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the

No differences in ventral striatum responsivity between adolescents with a positive family history of alcoholism and controls.

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Müller, Kathrin U; Gan, Gabriela; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Ströhle, Andreas; Struve, Maren; Schumann, Gunter; Smolka, Michael N

2015-05-01

Individuals with alcohol-dependent parents show an elevated risk of developing alcohol-related problems themselves. Modulations of the mesolimbic reward circuit have been postulated as a pre-existing marker of alcoholism. We tested whether a positive family history of alcoholism is correlated with ventral striatum functionality during a reward task. All participants performed a modified version of the monetary incentive delay task while their brain responses were measured with functional magnetic resonance imaging. We compared 206 healthy adolescents (aged 13-15) who had any first- or second-degree relative with alcoholism to 206 matched controls with no biological relative with alcoholism. Reward anticipation as well as feedback of win recruited the ventral striatum in all participants, but adolescents with a positive family history of alcoholism did not differ from their matched peers. Also we did not find any correlation between family history density and reward anticipation or feedback of win. This finding of no differences did not change when we analyzed a subsample of 77 adolescents with at least one parent with alcohol use disorder and their matched controls. Because this result is in line with another study reporting no differences between children with alcohol-dependent parents and controls at young age, but contrasts with studies of older individuals, one might conclude that at younger age the effect of family history has not yet exerted its influence on the still developing mesolimbic reward circuit. © 2014 Society for the Study of Addiction.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum

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Goldfarb, Elizabeth V.; Chun, Marvin M.; Phelps, Elizabeth A.

2016-01-01

Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial...

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

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Hoffmann, Hanne Mette; Crouzin, Nadine; Moreno, Estefanía; Raivio, Noora; Fuentes, Silvia; McCormick, Peter J.; Vignes, Michel

2017-01-01

Abstract Background: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise. Methods: We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission. Results: We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein. Interestingly, the group I metabotropic glutamate receptor antagonist/inverse-agonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride, led to a specific increase in cAMP responsive-element binding protein phosphorylation after chronic cocaine self-administration, specifically in the nucleus accumbens, but not in the striatum. Conclusions: Prolonged cocaine self-administration, through withdrawal, leads to a blunting of group I metabotropic glutamate receptor

Epistasis between QTLs for bone density variation in Copenhagen × dark agouti F2 rats

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Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J.; Foroud, Tatiana; Turner, Charles H.

2010-01-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation. PMID:19153792

Epistasis between QTLs for bone density variation in Copenhagen x dark agouti F2 rats.

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Koller, Daniel L; Liu, Lixiang; Alam, Imranul; Sun, Qiwei; Econs, Michael J; Foroud, Tatiana; Turner, Charles H

2009-03-01

The variation in several of the risk factors for osteoporotic fracture, including bone mineral density (BMD), has been shown to be strongly influenced by genetic differences. However, the genetic architecture of BMD is complex in both humans and in model organisms. We previously reported quantitative trait locus (QTL) results for BMD from a genome screen of 828 F2 progeny of Copenhagen and dark agouti rats. These progeny also provide an excellent opportunity to search for epistatic effects, or interaction between genetic loci, that contribute to fracture risk. Microsatellite marker data from a 20-cM genome screen was analyzed along with weight-adjusted bone density (DXA and pQCT) phenotypic data using the R/qtl software package. Genotype and phenotype data were permuted to determine genome-wide significance thresholds for the full model and epistasis (interaction) LOD scores corresponding to an alpha level of 0.01. A novel locus on chromosome 15 and a previously reported chromosome 14 QTL demonstrated a strong epistatic effect on BMD at the femur by DXA (LOD = 5.4). Two novel QTLs on chromosomes 2 and 12 were found to interact to affect total BMD at the femur midshaft by pQCT (LOD = 5.0). These results provide new information regarding the mode of action of previously identified QTL in the rat, as well as identifying novel loci that act in combination with known QTL or with other novel loci to contribute to BMD variation.

Equipment-independent reference values for dopamine transporter imaging with 123I-FP-CIT

International Nuclear Information System (INIS)

Koch, W.; Hornung, J.; Poepperl, G.; Tatsch, K.; Hamann, C.

2007-01-01

Aim: Reliable reference values are helpful to interpret and compare the results of dopamine transporter imaging with SPECT. Since semi-quantitative reference values cannot be easily transferred between imaging equipments, this study aimed to establish equipment independent normal values for the true striatal binding of 123 I-FP-CIT. Patients, methods: Specific striatal FP-CIT binding of 6 healthy volunteers and 26 patients with essential tremor were used to generate a reference range by applying an equipment specific resolution dependent factor to compensate for recovery effects. This factor has been determined previously by a series of standardized phantom measurements of an anthropomorphic basal ganglia phantom. Herewith, the resulting DAT binding values represent the expected true specific binding in the striatum. Results: On average, true specific striatal binding was 5.83 ± 0.96 in healthy controls, 5.25 ± 0.67 in patients with essential tremor and 5.36 ± 0.75 in the entire study cohort. Conclusion: These preliminary results may serve as a basis for the generation of a generally accepted equipment independent reference range for dopamine transporter imaging with 123 I-FP-CIT. By a simple phantom measurement that can be accomplished within one day factors related to specific imaging equipment and processing can be corrected for, resulting in specific binding values which may enable a more standardized interpretation of dopamine transporter scans. (orig.)

Identification and replication of loci involved in camptothecin-induced cytotoxicity using CEPH pedigrees.

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Venita Gresham Watson

2011-05-01

Full Text Available To date, the Centre d'Etude Polymorphism Humain (CEPH cell line model has only been used as a pharmacogenomic tool to evaluate which genes are responsible for the disparity in response to a single drug. The purpose of this study was demonstrate the model's ability to establish a specific pattern of quantitative trait loci (QTL related to a shared mechanism for multiple structurally related drugs, the camptothecins, which are Topoisomerase 1 inhibitors. A simultaneous screen of six camptothecin analogues for in vitro sensitivity in the CEPH cell lines resulted in cytotoxicity profiles and orders of potency which were in agreement with the literature. For all camptothecins studied, heritability estimates for cytotoxic response averaged 23.1 ± 2.6%. Nonparametric linkage analysis was used to identify a relationship between genetic markers and response to the camptothecins. Ten QTLs on chromosomes 1, 3, 5, 6, 11, 12, 16 and 20 were identified as shared by all six camptothecin analogues. In a separate validation experiment, nine of the ten QTLs were replicated at the significant and suggestive levels using three additional camptothecin analogues. To further refine this list of QTLs, another validation study was undertaken and seven of the nine QTLs were independently replicated for all nine camptothecin analogues. This is the first study using the CEPH cell lines that demonstrates that a specific pattern of QTLs could be established for a class of drugs which share a mechanism of action. Moreover, it is the first study to report replication of linkage results for drug-induced cytotoxicity using this model. The QTLs, which have been identified as shared by all camptothecins and replicated across multiple datasets, are of considerable interest; they harbor genes related to the shared mechanism of action for the camptothecins, which are responsible for variation in response.

INCREASES IN FUNCTIONAL CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND STRIATUM DURING CATEGORY LEARNING

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Antzoulatos, Evan G.; Miller, Earl K.

2014-01-01

SUMMARY Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is thought critical for cognition, and has been linked to conditions like autism and schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys acquired new categories. Category learning was accompanied by an increase in beta-band synchronization of LFPs between, but not within, the PFC and STR. After learning, different pairs of PFC-STR electrodes showed stronger synchrony for one or the other category, suggesting category-specific functional circuits. This category-specific synchrony was also seen between PFC spikes and STR LFPs, but not the reverse, reflecting the direct monosynaptic connections from the PFC to STR. However, causal connectivity analyses suggested that the polysynaptic connections from STR to the PFC exerted a stronger overall influence. This supports models positing that the basal ganglia “train” the PFC. Category learning may depend on the formation of functional circuits between the PFC and STR. PMID:24930701

Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

DEFF Research Database (Denmark)

Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

2011-01-01

It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...

The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

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Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

2007-08-15

Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

[Effect of Corydalis Rhizoma and L-tetrahydropalmatine on dopamine system of hippocampus and striatum in morphine-induced conditioned place preference rats].

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Yu, Shou-Yang; Bai, Wei-Feng; Tu, Ping; Qiu, Cheng-Kai; Yang, Pei-Run; Luo, Su-Yuan

2016-10-01

To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹). Models of CPP were validated in those psychological dependence rats after 48 h training. The dopamine contents were detected as soon as the materials of hippocampus and striatum are harvested from rats of NS control group and model group. The DAT and D2R levels are measured by Western blot. The high, medium and low dose group of Corydalis Rhizoma are given Corydalis Rhizoma 2, 1, 0.5 g•kg⁻¹ water extraction liquid respectively (which contains L-THP were 0.274, 0.137 and 0.137 mg respectively), and the high, medium and low dose group of L-THP were given L-THP 3.76, 1.88, 0.94 mg•kg⁻¹ lavage treatment respectively, NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP, again tested DA levels and expression of DAT and D2R similar to the front of materials. The reduction effects of CPP were observed in the groups of both Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) subjected to medicine for 6 days (Peffect of L-THP. The similar effects were observed on the neurotransmitter dopamine, DAT and D2R in learning and memory-related brain areas, hippocampus and striatum of the morphine- dependent rats. Copyright© by the Chinese Pharmaceutical Association.

In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

International Nuclear Information System (INIS)

Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

1988-01-01

The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states

Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

Energy Technology Data Exchange (ETDEWEB)

Hennies, H H; Hess, V; Flohe, L

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

[Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

Science.gov (United States)

Leontovich, T A; Zvegintseva, E G

1985-10-01

Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.

Proteomic Analysis of the Effect of Korean Red Ginseng in the Striatum of a Parkinson?s Disease Mouse Model

OpenAIRE

Kim, Dongsoo; Jeon, Hyongjun; Ryu, Sun; Koo, Sungtae; Ha, Ki-Tae; Kim, Seungtae

2016-01-01

Recent studies have shown that Korean Red Ginseng (KRG) suppresses dopaminergic neuronal death in the brain of a Parkinson's disease (PD) mouse model, but the mechanism is still elusive. Using a 2-dimensional electrophoresis technique, we investigated whether KRG can restore the changes in protein expressions in the striatum (ST) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Male C57BL/6 mice (9 weeks old) were injected with 20 mg/kg MPTP intraperitoneally four times a...

Genetic Variation and Association Analysis of the SSR Markers Linked to the Major Drought-Yield QTLs of Rice.

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Tabkhkar, Narjes; Rabiei, Babak; Samizadeh Lahiji, Habibollah; Hosseini Chaleshtori, Maryam

2018-02-24

Drought is one of the major abiotic stresses, which hampers the production of rice worldwide. Informative molecular markers are valuable tools for improving the drought tolerance in various varieties of rice. The present study was conducted to evaluate the informative simple sequence repeat (SSR) markers in a diverse set of rice genotypes. The genetic diversity analyses of the 83 studied rice genotypes were performed using 34 SSR markers closely linked to the major quantitative trait loci (QTLs) of grain yield under drought stress (qDTYs). In general, our results indicated high levels of polymorphism. In addition, we screened these rice genotypes at the reproductive stage under both drought stress and nonstressful conditions. The results of the regression analysis demonstrated a significant relationship between 11 SSR marker alleles and the plant paddy weight under stressful conditions. Under the nonstressful conditions, 16 SSR marker alleles showed a significant correlation with the plant paddy weight. Finally, four markers (RM279, RM231, RM166, and RM231) demonstrated a significant association with the plant paddy weight under both stressful and nonstressful conditions. These informative-associated alleles may be useful for improving the crop yield under both drought stress and nonstressful conditions in breeding programs.

Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum.

Science.gov (United States)

Liu, Jing; Parsons, Loren; Pope, Carey

2015-09-01

Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. Copyright © 2015 Elsevier Inc. All rights reserved.

Quinolinic acid induced neurodegeneration in the striatum: a combined in vivo and in vitro analysis of receptor changes and microglia activation

International Nuclear Information System (INIS)

Moresco, R.M.; Lavazza, T.; Belloli, S.; Todde, S.; Matarrese, M.; Carpinelli, A.; Turolla, E.; Fazio, F.; Lecchi, M.; Pezzola, A.; Popoli, P.; Zimarino, V.; Malgaroli, A.

2008-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this human neurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A 2A and dopamine D 2 receptors) together with the degree of microglia activation. Both approaches showed a loss of adenosine A 2A and dopamine D 2 receptors paralleled by an increase of microglial activation. This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to human patients. (orig.)

Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report

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Zangana Hero M

2011-07-01

Full Text Available Abstract Background Bilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse. Case presentation We report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission. Conclusion This is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

Fine-mapping resolves Eae23 into two QTLs and implicates ZEB1 as a candidate gene regulating experimental neuroinflammation in rat.

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Pernilla Stridh

Full Text Available BACKGROUND: To elucidate mechanisms involved in multiple sclerosis (MS, we studied genetic regulation of experimental autoimmune encephalomyelitis (EAE in rats, assuming a conservation of pathogenic pathways. In this study, we focused on Eae23, originally identified to regulate EAE in a (LEW.1AV1xPVG.1AV1F2 cross. Our aim was to determine whether one or more genes within the 67 Mb region regulate EAE and to define candidate risk genes. METHODOLOGY/PRINCIPAL FINDINGS: We used high resolution quantitative trait loci (QTL analysis in the 10th generation (G10 of an advanced intercross line (AIL to resolve Eae23 into two QTLs that independently regulate EAE, namely Eae23a and Eae23b. We established a congenic strain to validate the effect of this region on disease. PVG alleles in Eae23 resulted in significant protection from EAE and attenuated CNS inflammation/demyelination. Disease amelioration was accompanied with increased levels of Foxp3(+ cells in the CNS of the congenic strain compared to DA. We then focused on candidate gene investigation in Eae23b, a 9 Mb region linked to all clinical phenotypes. Affymetrix exon arrays were used to study expression of the genes in Eae23b in the parental strains, where none showed differential expression. However, we found lower expression of exon 4 of ZEB1, which is specific for splice-variant Zfhep1. ZEB1 is an interleukin 2 (IL2 repressor involved in T cell development. The splice-specific variance prompted us to next analyze the expression of ZEB1 and its two splice variants, Zfhep1 and Zfhep2, in both lymph node and spleen. We demonstrated that ZEB1 splice-variants are differentially expressed; severity of EAE and higher IL2 levels were associated with down-regulation of Zfhep1 and up-regulation of Zfhep2. CONCLUSIONS/SIGNIFICANCE: We speculate that the balance between splice-variants of ZEB1 could influence the regulation of EAE. Further functional studies of ZEB1 and the splice-variants may unravel

1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity.

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Lorenc-Koci, Elzbieta; Gołembiowska, Krystyna; Wardas, Jadwiga

2005-07-27

Malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, is frequently used as a model neurotoxin to produce lesion of the nigrostriatal dopaminergic system in animals due to particular sensitivity of dopamine neurons to mild energy impairment. This model of neurotoxicity was applied in our study to explore neuroprotective potential of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance whose function in the mammalian brain, despite extensive studies, has not been elucidated so far. Injection of malonate at a dose of 3 mumol unilaterally into the rat left medial forebrain bundle resulted in the 54% decrease in dopamine (DA) concentration in the ipsilateral striatum and, depending on the examined striatum regions, caused 24-44% reduction in [3H]GBR12,935 binding to the dopamine transporter (DAT). TIQ (50 mg/kg i.p.) administered 4 h before malonate infusion and next once daily for successive 7 days prevented both these effects of malonate. Such TIQ treatment restored DA content and DAT binding almost to the control level. The results of the present study indicate that TIQ may act as a neuroprotective agent in the rat brain. An inhibition of the enzymatic activities of monoamine oxidase and gamma-glutamyl transpeptidase as well as an increase in the striatal levels of glutathione and nitric oxide found after TIQ administration and reported in our earlier studies are considered to be potential factors that may be involved in the TIQ-mediated protection of dopamine terminals from malonate toxicity.

The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance

DEFF Research Database (Denmark)

Innocenti, Giorgio M.; Dyrby, Tim Bjørn; Andersen, Kasper Winther

2017-01-01

The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species......, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4–0.6 µm), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon...... diameters and conduction distance are monkey and, by extrapolation,

Decreased resting-state BOLD regional homogeneity and the intrinsic functional connectivity within dorsal striatum is associated with greater impulsivity in food-related decision-making and BMI change at 6-month follow up.

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Gao, Xiao; Liang, Qianlin; Wu, Guorong; She, Ying; Sui, Nan; Chen, Hong

2018-04-30

Increasing animal models as well as brain imaging studies among human suggest an association between substance-related impulsivity in decision-making and decreased function of dorsal striatum. However, the resting-state intrinsic functional organization of dorsal striatum underlying food-choice impulsivity remains unknown. To address this issue, we used resting-state functional MRI (rs-fMRI) to measure brain activity among adult females. Subjects underwent the food rating task, during which they rated each food item according to their subjective perception of its taste (from Dislike it very much to Like it very much), its long term effect on health (from very unhealthy to very healthy) and decision strength to eat it (from Strong no to Strong yes). Behaviorally, impulsivity in food-choice was indexed by the decision strength of the palatable high-calorie food rather than of the low-caloric food. Results on rs-fMRI showed that greater impulsivity in food-related decision-making was inversely correlated with spontaneous regional homogeneity in the dorsal striatum (dorsal caudate), as well as the resting-state functional connectivity (rs-FC) between the dorsal caudate seed and the rostral putamen. Furthermore, the caudate-putamen rs-FC inversely predicted BMI change at six-month follow-up. These findings may suggest the insensitivity to reward signals in dorsal caudate in decision-making coupled with an imbalance between goal-directed behaviors (modulated by dorsal caudate) and habitual actions (modulated by putamen) underlying impulsivity and future weight gain. In sum, these findings extend our understanding on the neural basis of food-related impulsivity, and provide evidence for the dorsal striatum as one of the landmarks in over eating and weight change. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic control of protein, oil and fatty acids content under partial ...

African Journals Online (AJOL)

The purpose of the present study was to map quantitative trait locus (QTLs) associated with percentage of seed protein, oil and fatty acids content under different conditions in a population of recombinant inbred lines (RILs) of sunflower. Three independent field experiments were conducted with well-, partial-irrigated and ...

Heritability and genetic basis of protein level variation in an outbred population.

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Parts, Leopold; Liu, Yi-Chun; Tekkedil, Manu M; Steinmetz, Lars M; Caudy, Amy A; Fraser, Andrew G; Boone, Charles; Andrews, Brenda J; Rosebrock, Adam P

2014-08-01

The genetic basis of heritable traits has been studied for decades. Although recent mapping efforts have elucidated genetic determinants of transcript levels, mapping of protein abundance has lagged. Here, we analyze levels of 4084 GFP-tagged yeast proteins in the progeny of a cross between a laboratory and a wild strain using flow cytometry and high-content microscopy. The genotype of trans variants contributed little to protein level variation between individual cells but explained >50% of the variance in the population's average protein abundance for half of the GFP fusions tested. To map trans-acting factors responsible, we performed flow sorting and bulk segregant analysis of 25 proteins, finding a median of five protein quantitative trait loci (pQTLs) per GFP fusion. Further, we find that cis-acting variants predominate; the genotype of a gene and its surrounding region had a large effect on protein level six times more frequently than the rest of the genome combined. We present evidence for both shared and independent genetic control of transcript and protein abundance: More than half of the expression QTLs (eQTLs) contribute to changes in protein levels of regulated genes, but several pQTLs do not affect their cognate transcript levels. Allele replacements of genes known to underlie trans eQTL hotspots confirmed the correlation of effects on mRNA and protein levels. This study represents the first genome-scale measurement of genetic contribution to protein levels in single cells and populations, identifies more than a hundred trans pQTLs, and validates the propagation of effects associated with transcript variation to protein abundance. © 2014 Parts et al.; Published by Cold Spring Harbor Laboratory Press.

A genome-wide association study identifies protein quantitative trait loci (pQTLs.

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David Melzer

2008-05-01

locations. The identification of protein quantitative trait loci (pQTLs may be a powerful complementary method of improving our understanding of disease pathways.

Validation of QTLs for Orobanche crenata resistance in faba bean (Vicia faba L.) across environments and generations.

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Díaz-Ruiz, Ramón; Torres, A M; Satovic, Z; Gutierrez, M V; Cubero, J I; Román, Belén

2010-03-01

Broomrape (Orobanche crenata Forsk.) is a major root-parasite of faba bean (Vicia faba L.), that seriously limits crop cultivation in the whole Mediterranean area. This parasitic weed is difficult to control, difficult to evaluate and the resistance identified so far is of polygenic nature. This study was conducted to identify genetic regions associated with broomrape resistance in recombinant inbred lines (RILs) and to validate their previous location in the original F(2) population derived from the cross between lines Vf6 and Vf136. A progeny consisting of 165 F(6) RILs was evaluated in three environments across two locations in 2003 and 2004. Two hundred seventy seven molecular markers were assigned to 21 linkage groups (9 of them assigned to specific chromosomes) that covered 2,856.7 cM of the V. faba genome. The composite interval mapping on the F(6) map detected more quantitative trait loci (QTL) than in the F(2) analysis. In this sense, four QTLs controlling O. crenata resistance (Oc2-Oc5) were identified in the RI segregant population in three different environments. Only Oc1, previously reported in the F(2) population, was not significant in the advanced lines. Oc2 and Oc3 were found to be associated with O. crenata resistance in at least two of the three environments, while the remaining two, Oc4 and Oc5, were only detected in Córdoba-04 and Mengíbar-04 and seemed to be environment dependent.

Mapping of Ppd-B1, a Major Candidate Gene for Late Heading on Wild Emmer Chromosome Arm 2BS and Assessment of Its Interactions with Early Heading QTLs on 3AL.

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Zhou, Wei; Wu, Shasha; Ding, Mingquan; Li, Jingjuan; Shi, Zhaobin; Wei, Wei; Guo, Jialian; Zhang, Hua; Jiang, Yurong; Rong, Junkang

2016-01-01

Wheat heading date is an important agronomic trait determining maturation time and yield. A set of common wheat (Triticum aestivum var. Chinese Spring; CS)-wild emmer (T. turgidum L. subsp. dicoccoides (TDIC)) chromosome arm substitution lines (CASLs) was used to identify and allocate QTLs conferring late or early spike emergence by examining heading date. Genetic loci accelerating heading were found on TDIC chromosome arms 3AL and 7BS, while loci delaying heading were located on 4AL and 2BS. To map QTLs conferring late heading on 2BS, F2 populations derived from two cross combinations of CASL2BS × CS and CASL3AL × CASL2BS were developed and each planted at two times, constituting four F2 mapping populations. Heading date varied continuously among individuals of these four populations, suggesting quantitative characteristics. A genetic map of 2BS, consisting of 23 SSR and one single-stranded conformation polymorphism (SSCP) marker(s), was constructed using these F2 populations. This map spanned a genetic length of 53.2 cM with average marker density of 2.3 cM. The photoperiod-sensitivity gene Ppd-B1 was mapped to chromosome arm 2BS as a SSCP molecular marker, and was validated as tightly linked to a major QTL governing late heading of CASL2BS in all mapping populations. A significant dominance by additive effect of Ppd-B1 with the LUX gene located on 3AL was also detected. CS had more copies of Ppd-B1 than CASL2BS, implying that increased copy number could elevate the expression of Ppd-1 in CS, also increasing expression of LUX and FT genes and causing CS to have an earlier heading date than CASL2BS in long days.

Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

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Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

2014-05-01

Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

Identification and validation of quantitative trait loci for seed yield, oil and protein contents in two recombinant inbred line populations of soybean.

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Wang, Xianzhi; Jiang, Guo-Liang; Green, Marci; Scott, Roy A; Song, Qijian; Hyten, David L; Cregan, Perry B

2014-10-01

Soybean seeds contain high levels of oil and protein, and are the important sources of vegetable oil and plant protein for human consumption and livestock feed. Increased seed yield, oil and protein contents are the main objectives of soybean breeding. The objectives of this study were to identify and validate quantitative trait loci (QTLs) associated with seed yield, oil and protein contents in two recombinant inbred line populations, and to evaluate the consistency of QTLs across different environments, studies and genetic backgrounds. Both the mapping population (SD02-4-59 × A02-381100) and validation population (SD02-911 × SD00-1501) were phenotyped for the three traits in multiple environments. Genetic analysis indicated that oil and protein contents showed high heritabilities while yield exhibited a lower heritability in both populations. Based on a linkage map constructed previously with the mapping population and using composite interval mapping and/or interval mapping analysis, 12 QTLs for seed yield, 16 QTLs for oil content and 11 QTLs for protein content were consistently detected in multiple environments and/or the average data over all environments. Of the QTLs detected in the mapping population, five QTLs for seed yield, eight QTLs for oil content and five QTLs for protein content were confirmed in the validation population by single marker analysis in at least one environment and the average data and by ANOVA over all environments. Eight of these validated QTLs were newly identified. Compared with the other studies, seven QTLs for seed yield, eight QTLs for oil content and nine QTLs for protein content further verified the previously reported QTLs. These QTLs will be useful for breeding higher yield and better quality cultivars, and help effectively and efficiently improve yield potential and nutritional quality in soybean.

Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

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Sara ePalm

2014-07-01

Full Text Available Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

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Tamakoshi, Keigo; Ishida, Kazuto; Kawanaka, Kentaro; Takamatsu, Yasuyuki; Tamaki, Hiroyuki

2017-10-01

We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Interest in politics modulates neural activity in the amygdala and ventral striatum.

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Gozzi, Marta; Zamboni, Giovanna; Krueger, Frank; Grafman, Jordan

2010-11-01

Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. © 2010 Wiley-Liss, Inc.

Are Independent Probes Truly Independent?

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Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

2009-01-01

The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

Directory of Open Access Journals (Sweden)

Victoria L Herrera

Full Text Available Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP quantitative trait loci (QTLs that co-localized with navigational performance (Nav-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5, diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5, and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5 compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05. The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

Sex-specific effects on spatial learning and memory, and sex-independent effects on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt-sensitive rats.

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Herrera, Victoria L; Pasion, Khristine A; Tan, Glaiza A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9 mmHg, P<1×10(-5)), diastolic blood pressure (females: -21.2 mmHg, P = 0.01; males: -25.7 mmHg, P<1×10(-5)), and mean arterial pressure (females: -23.9 mmHg, P = 0.004; males: -28.0 mmHg, P<1×10(-5)) compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male congenic rats when compared with Dahl S male controls (P<0.05). The S.R2B congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

Distinct changes in CREB phosphorylation in frontal cortex and striatum during contingent and non-contingent performance of a visual attention task

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Mirjana eCarli

2011-10-01

Full Text Available The cyclic-AMP response element binding protein (CREB family of transcription factors has been implicated in numerous forms of behavioural plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC and dorsal (caudate putamen, CPu and ventral (nucleus accumbens, NAC striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, master, a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, yoked and a control group matched for food deprivation and exposure to the test apparatus (untrained. Rats trained on the 5-CSRTT (both master and yoked had higher levels of CREB protein in the FC, CPu and NAC compared to untrained controls. Despite the divergent behaviour of master and yoked rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (master, CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (yoked. The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

2016-03-01

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats.

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Saund, Jasjot; Dautan, Daniel; Rostron, Claire; Urcelay, Gonzalo P; Gerdjikov, Todor V

2017-08-01

Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control.

From the ventral to the dorsal striatum: devolving views of their roles in drug addiction.

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Everitt, Barry J; Robbins, Trevor W

2013-11-01

We revisit our hypothesis that drug addiction can be viewed as the endpoint of a series of transitions from initial voluntarily drug use to habitual, and ultimately compulsive drug use. We especially focus on the transitions in striatal control over drug seeking behaviour that underlie these transitions since functional heterogeneity of the striatum was a key area of Ann Kelley's research interests and one in which she made enormous contributions. We also discuss the hypothesis in light of recent data that the emergence of a compulsive drug seeking habit both reflects a shift to dorsal striatal control over behaviour and impaired prefontal cortical inhibitory control mechanisms. We further discuss aspects of the vulnerability to compulsive drug use and in particular the impact of impulsivity. In writing this review we acknowledge the untimely death of an outstanding scientist and a dear personal friend. Copyright © 2013 Elsevier Ltd. All rights reserved.

Representation of the body in the lateral striatum of the freely moving rat: Fast Spiking Interneurons respond to stimulation of individual body parts.

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Kulik, Julianna M; Pawlak, Anthony P; Kalkat, Manraj; Coffey, Kevin R; West, Mark O

2017-02-15

Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input

Metabolism of glucose in brain of patients with Parkinson's disease. Studies on /sup 11/C-glucose metabolism in the striatum and cerebral cortex during medication or interruption of medication by positron emission computed tomography

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Yokoi, Fuji; Ando, Kazuya; Iio, Masaaki

1984-12-01

We examined /sup 11/C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with /sup 11/C-Glucose (per os). /sup 11/C-Glucose was prepared from /sup 11/CO/sub 2/ by photosynthesis. 1) No significant difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the /sup 11/C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author).

Contingency learning in human fear conditioning involves the ventral striatum.

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Klucken, Tim; Tabbert, Katharina; Schweckendiek, Jan; Merz, Christian Josef; Kagerer, Sabine; Vaitl, Dieter; Stark, Rudolf

2009-11-01

The ability to detect and learn contingencies between fearful stimuli and their predictive cues is an important capacity to cope with the environment. Contingency awareness refers to the ability to verbalize the relationships between conditioned and unconditioned stimuli. Although there is a heated debate about the influence of contingency awareness on conditioned fear responses, neural correlates behind the formation process of contingency awareness have gained only little attention in human fear conditioning. Recent animal studies indicate that the ventral striatum (VS) could be involved in this process, but in human studies the VS is mostly associated with positive emotions. To examine this question, we reanalyzed four recently published classical fear conditioning studies (n = 117) with respect to the VS at three distinct levels of contingency awareness: subjects, who did not learn the contingencies (unaware), subjects, who learned the contingencies during the experiment (learned aware) and subjects, who were informed about the contingencies in advance (instructed aware). The results showed significantly increased activations in the left and right VS in learned aware compared to unaware subjects. Interestingly, this activation pattern was only found in learned but not in instructed aware subjects. We assume that the VS is not involved when contingency awareness does not develop during conditioning or when contingency awareness is unambiguously induced already prior to conditioning. VS involvement seems to be important for the transition from a contingency unaware to a contingency aware state. Implications for fear conditioning models as well as for the contingency awareness debate are discussed.

The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption.

Science.gov (United States)

Cole, Sindy; Stone, Andrew D; Petrovich, Gorica D

2017-12-01

The dorsomedial striatum (DMS) is an important sensorimotor region mediating the acquisition of goal-directed instrumental reward learning and behavioral flexibility. However, whether the DMS also regulates Pavlovian cue-food learning is less clear. The current study used excitotoxic lesions to determine whether the DMS is critical in Pavlovian appetitive learning and behavior, using discriminative conditioning and reversal paradigms. The results showed that DMS lesions transiently retarded cue-food learning and subsequent reversal of this learning. Rats with DMS lesions selectively attenuated responding to a food cue but not a control cue, early in training, suggesting the DMS is involved when initial associations are formed. Similarly, initial reversal learning was attenuated in rats with DMS lesions, which suggests impaired flexibility to adjust behavior when the cue meaning is reversed. We also examined the effect of DMS lesions on food intake during tests with access to a highly palatable food along with standard chow diet. Rats with DMS lesions showed an altered pattern of intake, with an initial reduction in high-fat diet followed by an increase in chow consumption. These results demonstrate that the DMS has a role in mediating cue-food learning and its subsequent reversal, as well as changes in food intake when a choice is provided. Together, these results demonstrate the DMS is involved in reward associative learning and reward consumption, when behavioral flexibility is needed to adjust responding or consumption to match the current value. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs

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Le Clerc, Sigrid; van Manen, Daniëlle; Coulonges, Cédric; Ulveling, Damien; Laville, Vincent; Labib, Taoufik; Taing, Lieng; Delaneau, Olivier; Montes, Matthieu; Schuitemaker, Hanneke; Zagury, Jean-François

2015-01-01

Background Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS. Methods We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate. Results Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV. PMID:26367535

Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs.

Directory of Open Access Journals (Sweden)

Jean-Louis Spadoni

Full Text Available Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS.We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate.Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%. Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV.

Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

International Nuclear Information System (INIS)

Goeders, N.E.; Kuhar, M.J.

1987-01-01

A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of [ 3 H]sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems

Chemical Exchange Saturation Transfer MR Imaging Is Superior to Diffusion Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: a Study on Substantia Nigra and Striatum

Directory of Open Access Journals (Sweden)

Chunmei eLi

2015-10-01

Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date the diagnosis of PD is still based primarily on the clinical manifestations which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical-exchange-saturation-transfer (CEST imaging and diffusion-tensor imaging (DTI in PD at 3 Tesla by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3 Tesla MR system, using an 8-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm, and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen and caudate. The MTRasym(3.5ppm value, the total CEST signal intensity and fractional anisotropy (FA value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004 and P < 0.001, respectively. The MTRasym(3.5ppm values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively. There were no significant differences for the mean diffusivity (MD in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum

DEFF Research Database (Denmark)

Deserno, Lorenz; Beck, Anne; Huys, Quentin J. M.

2015-01-01

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug......-related stimuli towards drug-related stimuli. Such ‘hijacked’ dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs......) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[18F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation...

Tyrosine-induced release of dopamine is under inhibitory control of presynaptic dopamine D2 and, probably, D3 receptors in the dorsal striatum, but not in the nucleus accumbens.

NARCIS (Netherlands)

Fusa, K.; Saigusa, T.; Koshikawa, N.; Cools, A.R.

2002-01-01

Stimulation of dopamine D2-like receptors decreases extracellular dopamine in the dorsal striatum and the nucleus accumbens. It is unknown whether the role of these receptors differs from that of dopamine D3 receptors. It is also unknown to what extent the role of these two types of receptors varies

Tyrosine-induced release of dopamine is under inhibitory control of presynaptic dopamine D2 and, probably, D3 receptors in the dorsal striatum, but not in the nucleus accumbens

NARCIS (Netherlands)

Fusa, K.; Saigusa, T.; Koshikawa, N.; Cools, A.R.

2002-01-01

Stimulation of dopamine D2-like receptors decreases extracellular dopamine in the dorsal striatum and the nucleus accumbens. It is unknown whether the role of these receptors differs from that of dopamine D3 receptors. It is also unknown to what extent the role of these two types of receptors varies

Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia.

Science.gov (United States)

Holubiec, Mariana I; Romero, Juan I; Blanco, Eduardo; Tornatore, Tamara Logica; Suarez, Juan; Rodríguez de Fonseca, Fernando; Galeano, Pablo; Capani, Francisco

2017-07-13

Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of QTLs Associated with Callogenesis and Embryogenesis in Oil Palm Using Genetic Linkage Maps Improved with SSR Markers

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Ting, Ngoot-Chin; Jansen, Johannes; Nagappan, Jayanthi; Ishak, Zamzuri; Chin, Cheuk-Weng; Tan, Soon-Guan; Cheah, Suan-Choo; Singh, Rajinder

2013-01-01

Clonal reproduction of oil palm by means of tissue culture is a very inefficient process. Tissue culturability is known to be genotype dependent with some genotypes being more amenable to tissue culture than others. In this study, genetic linkage maps enriched with simple sequence repeat (SSR) markers were developed for dura (ENL48) and pisifera (ML161), the two fruit forms of oil palm, Elaeis guineensis. The SSR markers were mapped onto earlier reported parental maps based on amplified fragment length polymorphism (AFLP) and restriction fragment length polymorphism (RFLP) markers. The new linkage map of ENL48 contains 148 markers (33 AFLPs, 38 RFLPs and 77 SSRs) in 23 linkage groups (LGs), covering a total map length of 798.0 cM. The ML161 map contains 240 markers (50 AFLPs, 71 RFLPs and 119 SSRs) in 24 LGs covering a total of 1,328.1 cM. Using the improved maps, two quantitative trait loci (QTLs) associated with tissue culturability were identified each for callusing rate and embryogenesis rate. A QTL for callogenesis was identified in LGD4b of ENL48 and explained 17.5% of the phenotypic variation. For embryogenesis rate, a QTL was detected on LGP16b in ML161 and explained 20.1% of the variation. This study is the first attempt to identify QTL associated with tissue culture amenity in oil palm which is an important step towards understanding the molecular processes underlying clonal regeneration of oil palm. PMID:23382832

The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats.

Science.gov (United States)

Ahmed, Nawal A; Radwan, Nasr M; Aboul Ezz, Heba S; Salama, Noha A

2017-01-01

Electromagnetic radiation (EMR) of cellular phones may affect biological systems by increasing free radicals and changing the antioxidant defense systems of tissues, eventually leading to oxidative stress. Green tea has recently attracted significant attention due to its health benefits in a variety of disorders, ranging from cancer to weight loss. Thus, the aim of the present study was to investigate the effect of EMR (frequency 900 MHz modulated at 217 Hz, power density 0.02 mW/cm 2 , SAR 1.245 W/kg) on different oxidative stress parameters in the hippocampus and striatum of adult rats. This study also extends to evaluate the therapeutic effect of green tea mega EGCG on the previous parameters in animals exposed to EMR after and during EMR exposure. The experimental animals were divided into four groups: EMR-exposed animals, animals treated with green tea mega EGCG after 2 months of EMR exposure, animals treated with green tea mega EGCG during EMR exposure and control animals. EMR exposure resulted in oxidative stress in the hippocampus and striatum as evident from the disturbances in oxidant and antioxidant parameters. Co-administration of green tea mega EGCG at the beginning of EMR exposure for 2 and 3 months had more beneficial effect against EMR-induced oxidative stress than oral administration of green tea mega EGCG after 2 months of exposure. This recommends the use of green tea before any stressor to attenuate the state of oxidative stress and stimulate the antioxidant mechanism of the brain.

Reward-Related Ventral Striatum Activity Buffers against the Experience of Depressive Symptoms Associated with Sleep Disturbances.

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Avinun, Reut; Nevo, Adam; Knodt, Annchen R; Elliott, Maxwell L; Radtke, Spenser R; Brigidi, Bartholomew D; Hariri, Ahmad R

2017-10-04

Sleep disturbances represent one risk factor for depression. Reward-related brain function, particularly the activity of the ventral striatum (VS), has been identified as a potential buffer against stress-related depression. We were therefore interested in testing whether reward-related VS activity would moderate the effect of sleep disturbances on depression in a large cohort of young adults. Data were available from 1129 university students (mean age 19.71 ± 1.25 years; 637 women) who completed a reward-related functional MRI task to assay VS activity and provided self-reports of sleep using the Pittsburgh Sleep Quality Index and symptoms of depression using a summation of the General Distress/Depression and Anhedonic Depression subscales of the Mood and Anxiety Symptoms Questionnaire-short form. Analyses revealed that as VS activity increased the association between sleep disturbances and depressive symptoms decreased. The interaction between sleep disturbances and VS activity was robust to the inclusion of sex, age, race/ethnicity, past or present clinical disorder, early and recent life stress, and anxiety symptoms, as well as the interactions between VS activity and early or recent life stress as covariates. We provide initial evidence that high reward-related VS activity may buffer against depressive symptoms associated with poor sleep. Our analyses help advance an emerging literature supporting the importance of individual differences in reward-related brain function as a potential biomarker of relative risk for depression. SIGNIFICANCE STATEMENT Sleep disturbances are a common risk factor for depression. An emerging literature suggests that reward-related activity of the ventral striatum (VS), a brain region critical for motivation and goal-directed behavior, may buffer against the effect of negative experiences on the development of depression. Using data from a large sample of 1129 university students we demonstrate that as reward-related VS activity

Genetic and Molecular Mechanisms of Quantitative Trait Loci Controlling Maize Inflorescence Architecture.

Science.gov (United States)

Li, Manfei; Zhong, Wanshun; Yang, Fang; Zhang, Zuxin

2018-03-01

The establishment of inflorescence architecture is critical for the reproduction of flowering plant species. The maize plant generates two types of inflorescences, the tassel and the ear, and their architectures have a large effect on grain yield and yield-related traits that are genetically controlled by quantitative trait loci (QTLs). Since ear and tassel architecture are deeply affected by the activity of inflorescence meristems, key QTLs and genes regulating meristematic activity have important impacts on inflorescence development and show great potential for optimizing grain yield. Isolation of yield trait-related QTLs is challenging, but these QTLs have direct application in maize breeding. Additionally, characterization and functional dissection of QTLs can provide genetic and molecular knowledge of quantitative variation in inflorescence architecture. In this review, we summarize currently identified QTLs responsible for the establishment of ear and tassel architecture and discuss the potential genetic control of four ear-related and four tassel-related traits. In recent years, several inflorescence architecture-related QTLs have been characterized at the gene level. We review the mechanisms of these characterized QTLs.

A functional difference in information processing between orbitofrontal cortex and ventral striatum during decision-making behaviour.

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Stott, Jeffrey J; Redish, A David

2014-11-05

Both orbitofrontal cortex (OFC) and ventral striatum (vStr) have been identified as key structures that represent information about value in decision-making tasks. However, the dynamics of how this information is processed are not yet understood. We recorded ensembles of cells from OFC and vStr in rats engaged in the spatial adjusting delay-discounting task, a decision-making task that involves a trade-off between delay to and magnitude of reward. Ventral striatal neural activity signalled information about reward before the rat's decision, whereas such reward-related signals were absent in OFC until after the animal had committed to its decision. These data support models in which vStr is directly involved in action selection, but OFC processes decision-related information afterwards that can be used to compare the predicted and actual consequences of behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

QTL variations for growth-related traits in eight distinct families of common carp (Cyprinus carpio).

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Lv, Weihua; Zheng, Xianhu; Kuang, Youyi; Cao, Dingchen; Yan, Yunqin; Sun, Xiaowen

2016-05-05

Comparing QTL analyses of multiple pair-mating families can provide a better understanding of important allelic variations and distributions. However, most QTL mapping studies in common carp have been based on analyses of individual families. In order to improve our understanding of heredity and variation of QTLs in different families and identify important QTLs, we performed QTL analysis of growth-related traits in multiple segregating families. We completed a genome scan for QTLs that affect body weight (BW), total length (TL), and body thickness (BT) of 522 individuals from eight full-sib families using 250 microsatellites evenly distributed across 50 chromosomes. Sib-pair and half-sib model mapping identified 165 QTLs on 30 linkage groups. Among them, 10 (genome-wide P <0.01 or P < 0.05) and 28 (chromosome-wide P < 0.01) QTLs exhibited significant evidence of linkage, while the remaining 127 exhibited a suggestive effect on the above three traits at a chromosome-wide (P < 0.05) level. Multiple QTLs obtained from different families affect BW, TL, and BT and locate at close or identical positions. It suggests that same genetic factors may control variability in these traits. Furthermore, the results of the comparative QTL analysis of multiple families showed that one QTL was common in four of the eight families, nine QTLs were detected in three of the eight families, and 26 QTLs were found common to two of the eight families. These common QTLs are valuable candidates in marker-assisted selection. A large number of QTLs were detected in the common carp genome and associated with growth-related traits. Some of the QTLs of different growth-related traits were identified at similar chromosomal regions, suggesting a role for pleiotropy and/or tight linkage and demonstrating a common genetic basis of growth trait variations. The results have set up an example for comparing QTLs in common carp and provided insights into variations in the identified QTLs

Microglial and macrophage reactions mark progressive changes and define the penumbra in the rat neocortex and striatum after transient middle cerebral artery occlusion

DEFF Research Database (Denmark)

Lehrmann, E; Christensen, Thomas; Zimmer, J

1997-01-01

Transient middle cerebral artery occlusion in rats leads to infarction of the lateral part of the striatum and adjacent neocortex, with selective neuronal necrosis in the bordering penumbral zones. Administration of glutamate, cytokine, and leukocyte antagonists have rescued mainly neocortical....../macrophages in the adjacent penumbra. Within the neocortex, a later onset of degeneration along the insular-parietal axis was marked by neuronal expression of heat shock protein and a progressive microglial activation with induction of the full repertoire of microglial activation markers, including a widespread microglial...

Distinct Reward Properties are Encoded via Corticostriatal Interactions

OpenAIRE

David V. Smith; Anastasia E. Rigney; Mauricio R. Delgado

2016-01-01

The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nu...

Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum.

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Melani, Alessia; Corti, Francesca; Stephan, Holger; Müller, Christa E; Donati, Chiara; Bruni, Paola; Vannucchi, Maria Giuliana; Pedata, Felicita

2012-01-01

In the central nervous system (CNS) ATP and adenosine act as transmitters and neuromodulators on their own receptors but it is still unknown which part of extracellular adenosine derives per se from cells and which part is formed from the hydrolysis of released ATP. In this study extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under in vivo physiological conditions and after focal ischemia induced by medial cerebral artery occlusion. Under physiological conditions, adenosine and ATP concentrations were in the range of 130 nmol/L and 40 nmol/L, respectively. In the presence of the novel ecto-ATPase inhibitor, PV4 (100 nmol/L), the extracellular concentration of ATP increased 12-fold to ~360 nmol/L but the adenosine concentration was not altered. This demonstrates that, under physiological conditions, adenosine is not a product of extracellular ATP. In the first 4h after ischemia, adenosine increased to ~690 nmol/L and ATP to ~50 nmol/L. In the presence of PV4 the extracellular concentration of ATP was in the range of 450 nmol/L and a significant decrease in extracellular adenosine (to ~270 nmol/L) was measured. The contribution of extracellular ATP to extracellular adenosine was maximal in the first 20 min after ischemia onset. Furthermore we demonstrated, by immunoelectron microscopy, the presence of the concentrative nucleoside transporter CNT2 on plasma and vesicle membranes isolated from the rat striatum. These results are in favor that adenosine is transported in vesicles and is released in an excitation-secretion manner under in vivo physiological conditions. Early after ischemia, extracellular ATP is hydrolyzed by ecto-nucleotidases which significantly contribute to the increase in extracellular adenosine. To establish the contribution of extracellular ATP to adenosine might constitute the basis for devising a correct putative purinergic strategy aimed at protection from ischemic damage

Are Independent Fiscal Institutions Really Independent?

Directory of Open Access Journals (Sweden)

Slawomir Franek

2015-08-01

Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity

Science.gov (United States)

Baranger, David A. A.; Ifrah, Chloé; Prather, Aric A.; Carey, Caitlin E.; Corral-Frías, Nadia S.; Drabant Conley, Emily; Hariri, Ahmad R.; Bogdan, Ryan

2016-01-01

Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions. PMID:27065929

PER1 rs3027172 genotype interacts with early life stress to predict problematic alcohol use, but not reward-related ventral striatum activity

Directory of Open Access Journals (Sweden)

David eBaranger

2016-03-01

Full Text Available Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (n=665, we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test as well as ventral striatum (VS reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired. Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene x covariate and environment x covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p<0.05, corrected while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, early life stress, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene x environment interactions.

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors

Science.gov (United States)

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2016-01-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ9-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of meth-amphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24709540

Expression of c-fos and c-jun proteins in the marginal division of the rat striatum during learning and memory training

Institute of Scientific and Technical Information of China (English)

BAO Xin-min; SHU Si-yun; WANG Hong

2005-01-01

Background A new brain region, the marginal division (MrD), was discovered at the caudal margin of the neostriatum. The MrD was shown to be involved in learning and memory in the rat. The aim of this study was to investigate the expression of the immediate-early genes c-fos and c-jun in the MrD of the striatum during learning and memory processes in the rat, immunocytochemical and Western blot methods were used to examine Y-maze trained rats.Methods The rats were divided into three groups, namely the training, pseudotraining, and control groups. After Y-maze training, the expression of the immediate-early genes c-fos and c-jun in the MrD of the rats was investigated using immunocytochemical and Western blot methods. Results After one hour of Y-maze training, the expression of c-jun and c-fos proteins was significantly enhanced in the MrD; the c-jun protein, in particular, was more intensely expressed in this region than in other parts of the striatum. The expression of these two proteins in the training group was significantly higher than in the pseudotraining and control groups. In addition, positive expression was also found in the hippocampus, cingulum cortex, thalamus, and in other areas. Western blot disclosed two immunoreactive bands for the anti-c-fos antibody (47 kD and 54 kD) and two immunoreactive bands for the anti-c-jun antibody (39 kD and 54 kD). Conclusions These results indicate that the immediate-early genes c-fos and c-jun participate in signal transduction during the learning and memory processes associated with Y-maze training in rats.

QTL mapping of root traits in phosphorus-deficient soils reveals important genomic regions for improving NDVI and grain yield in barley.

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Gong, Xue; McDonald, Glenn

2017-09-01

Major QTLs for root rhizosheath size are not correlated with grain yield or yield response to phosphorus. Important QTLs were found to improve phosphorus efficiency. Root traits are important for phosphorus (P) acquisition, but they are often difficult to characterize and their breeding values are seldom assessed under field conditions. This has shed doubts on using seedling-based criteria of root traits to select and breed for P efficiency. Eight root traits were assessed under controlled conditions in a barley doubled-haploid population in soils differing in P levels. The population was also phenotyped for grain yield, normalized difference vegetation index (NDVI), grain P uptake and P utilization efficiency at maturity (PutE GY ) under field conditions. Several quantitative traits loci (QTLs) from the root screening and the field trials were co-incident. QTLs for root rhizosheath size and root diameter explained the highest phenotypic variation in comparison to QTLs for other root traits. Shared QTLs were found between root diameter and grain yield, and total root length and PutE GY . A common major QTL for rhizosheath size and NDVI was mapped to the HvMATE gene marker on chromosome 4H. Collocations between major QTLs for NDVI and grain yield were detected on chromosomes 6H and 7H. When results from BIP and MET were combined, QTLs detected for grain yield were also those QTLs found for NDVI. QTLs qGY5H, qGY6H and qGY7Hb on 7H were robust QTLs in improving P efficiency. A selection of multiple loci may be needed to optimize the breeding outcomes due to the QTL x Environment interaction. We suggest that rhizosheath size alone is not a reliable trait to predict P efficiency or grain yield.

Expression variation in connected recombinant populations of Arabidopsis thaliana highlights distinct transcriptome architectures

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Cubillos Francisco A

2012-03-01

Full Text Available Abstract Background Expression traits can vary quantitatively between individuals and have a complex inheritance. Identification of the genetics underlying transcript variation can help in the understanding of phenotypic variation due to genetic factors regulating transcript abundance and shed light into divergence patterns. So far, only a limited number of studies have addressed this subject in Arabidopsis, with contrasting results due to dissimilar statistical power. Here, we present the transcriptome architecture in leaf tissue of two RIL sets obtained from a connected-cross design involving 3 commonly used accessions. We also present the transcriptome architecture observed in developing seeds of a third independent cross. Results The utilisation of the novel R/eqtl package (which goal is to automatize and extend functions from the R/qtl package allowed us to map 4,290 and 6,534 eQTLs in the Cvi-0 × Col-0 and Bur-0 × Col-0 recombinant populations respectively. In agreement with previous studies, we observed a larger phenotypic variance explained by eQTLs in linkage with the controlled gene (potentially cis-acting, compared to distant loci (acting necessarily indirectly or in trans. Distant eQTLs hotspots were essentially not conserved between crosses, but instead, cross-specific. Accounting for confounding factors using a probabilistic approach (VBQTL increased the mapping resolution and the number of significant associations. Moreover, using local eQTLs obtained from this approach, we detected evidence for a directional allelic effect in genes with related function, where significantly more eQTLs than expected by chance were up-regulated from one of the accessions. Primary experimental data, analysis parameters, eQTL results and visualisation of LOD score curves presented here are stored and accessible through the QTLstore service database http://qtlstore.versailles.inra.fr/. Conclusions Our results demonstrate the extensive diversity and

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

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Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

1995-12-01

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

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González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

2013-10-25

Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

Effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum

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Martin-Iverson, M.T.; Radke, J.M.; Vincent, S.R.

1986-06-01

The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin.

Identification of QTLs associated with callogenesis and embryogenesis in oil palm using genetic linkage maps improved with SSR markers.

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Ngoot-Chin Ting

Full Text Available Clonal reproduction of oil palm by means of tissue culture is a very inefficient process. Tissue culturability is known to be genotype dependent with some genotypes being more amenable to tissue culture than others. In this study, genetic linkage maps enriched with simple sequence repeat (SSR markers were developed for dura (ENL48 and pisifera (ML161, the two fruit forms of oil palm, Elaeis guineensis. The SSR markers were mapped onto earlier reported parental maps based on amplified fragment length polymorphism (AFLP and restriction fragment length polymorphism (RFLP markers. The new linkage map of ENL48 contains 148 markers (33 AFLPs, 38 RFLPs and 77 SSRs in 23 linkage groups (LGs, covering a total map length of 798.0 cM. The ML161 map contains 240 markers (50 AFLPs, 71 RFLPs and 119 SSRs in 24 LGs covering a total of 1,328.1 cM. Using the improved maps, two quantitative trait loci (QTLs associated with tissue culturability were identified each for callusing rate and embryogenesis rate. A QTL for callogenesis was identified in LGD4b of ENL48 and explained 17.5% of the phenotypic variation. For embryogenesis rate, a QTL was detected on LGP16b in ML161 and explained 20.1% of the variation. This study is the first attempt to identify QTL associated with tissue culture amenity in oil palm which is an important step towards understanding the molecular processes underlying clonal regeneration of oil palm.

Mindfulness meditation modulates reward prediction errors in the striatum in a passive conditioning task

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Ulrich eKirk

2015-02-01

Full Text Available Reinforcement learning models have demonstrated that phasic activity of dopamine neurons during reward expectation encodes information about the predictability of rewards and cues that predict reward. Evidence indicates that mindfulness-based approaches reduce reward anticipation signal in the striatum to negative and positive incentives suggesting the hypothesis that such training influence basic reward processing. Using a passive conditioning task and fMRI in a group of experienced mindfulness meditators and age-matched controls, we tested the hypothesis that mindfulness meditation influence reward and reward prediction error signals. We found diminished positive and negative prediction error-related blood-oxygen level-dependent (BOLD responses in the putamen in meditators compared with controls. In the meditators, this decrease in striatal BOLD responses to reward prediction was paralleled by increased activity in posterior insula, a primary interoceptive region. Critically, responses in the putamen during early trials of the conditioning procedure (run 1 were elevated in both meditators and controls. These results provide evidence that experienced mindfulness meditators show attenuated reward prediction signals to valenced stimuli, which may be related to interoceptive processes encoded in the posterior insula.

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

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Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease.

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Jonathan Wills

2011-03-01

Full Text Available Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of

Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia.

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Chung, Yu Sun; Barch, Deanna M

2016-04-01

Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue-related activations in several regions of the basal ganglia responding to reward-predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. (c) 2016 APA, all rights reserved).

Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

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Pierre eTrifilieff

2013-06-01

Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

Database Description - Q-TARO | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available hed research papers. From 1214 reports, we selected 5096 QTLs. The positions of t...s, as of March 31 of 2008, we selected 1051 QTLs extracted from 463 reports as representative QTLs. To arran

PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow

International Nuclear Information System (INIS)

Hassoun, Wadad; Ginovart, Nathalie; Zimmer, Luc; Gualda, Veronique; Bonnefoi, Frederic; Le Cavorsin, Marion; Leviel, Vincent

2003-01-01

Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [ 11 C]raclopride (BP raclo ), a radioligand with good specificity for dopamine (DA) receptors of the D 2 type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg -1 h -1 ; i.m.) and anaesthetised with halothane (1.5%). Non-specific binding was evaluated in the cerebellum. In the striatum of both sides, the BP raclo was unmodified by ketamine anaesthesia when compared with awake animals. In contrast, a large increase in BP raclo was observed under halothane anaesthesia. The non-specific binding of [ 11 C]raclopride, evaluated in the cerebellum, was also unchanged under ketamine anaesthesia but greatly increased under halothane anaesthesia. To evaluate whether changes in the cerebral blood flow (CBF) resulting from the different experimental situations could be at the root of these discrepancies, injections of [ 15 O]H 2 O were performed; measurements revealed a drastically increased CBF under halothane anaesthesia and a slight enhancement under ketamine anaesthesia, when compared with the waking state. These results are the first to be obtained on this topic in awake cats, and show that the BP raclo is greatly dependent on alterations in the CBF. (orig.)

The Conserved and Unique Genetic Architecture of Kernel Size and Weight in Maize and Rice.

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Liu, Jie; Huang, Juan; Guo, Huan; Lan, Liu; Wang, Hongze; Xu, Yuancheng; Yang, Xiaohong; Li, Wenqiang; Tong, Hao; Xiao, Yingjie; Pan, Qingchun; Qiao, Feng; Raihan, Mohammad Sharif; Liu, Haijun; Zhang, Xuehai; Yang, Ning; Wang, Xiaqing; Deng, Min; Jin, Minliang; Zhao, Lijun; Luo, Xin; Zhou, Yang; Li, Xiang; Zhan, Wei; Liu, Nannan; Wang, Hong; Chen, Gengshen; Li, Qing; Yan, Jianbing

2017-10-01

Maize ( Zea mays ) is a major staple crop. Maize kernel size and weight are important contributors to its yield. Here, we measured kernel length, kernel width, kernel thickness, hundred kernel weight, and kernel test weight in 10 recombinant inbred line populations and dissected their genetic architecture using three statistical models. In total, 729 quantitative trait loci (QTLs) were identified, many of which were identified in all three models, including 22 major QTLs that each can explain more than 10% of phenotypic variation. To provide candidate genes for these QTLs, we identified 30 maize genes that are orthologs of 18 rice ( Oryza sativa ) genes reported to affect rice seed size or weight. Interestingly, 24 of these 30 genes are located in the identified QTLs or within 1 Mb of the significant single-nucleotide polymorphisms. We further confirmed the effects of five genes on maize kernel size/weight in an independent association mapping panel with 540 lines by candidate gene association analysis. Lastly, the function of ZmINCW1 , a homolog of rice GRAIN INCOMPLETE FILLING1 that affects seed size and weight, was characterized in detail. ZmINCW1 is close to QTL peaks for kernel size/weight (less than 1 Mb) and contains significant single-nucleotide polymorphisms affecting kernel size/weight in the association panel. Overexpression of this gene can rescue the reduced weight of the Arabidopsis ( Arabidopsis thaliana ) homozygous mutant line in the AtcwINV2 gene (Arabidopsis ortholog of ZmINCW1 ). These results indicate that the molecular mechanisms affecting seed development are conserved in maize, rice, and possibly Arabidopsis. © 2017 American Society of Plant Biologists. All Rights Reserved.

Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

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Emson, P C; Westmore, K; Augood, S J [MRC Molecular Neuroscience Group, The Department of Neurobiology, The Babraham Institute, Babraham, Cambridge (United Kingdom)

1996-12-11

The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [{sup 35}S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [{sup 35}S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase

Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

International Nuclear Information System (INIS)

Emson, P.C.; Westmore, K.; Augood, S.J.

1996-01-01

The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [ 35 S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [ 35 S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase-positive cells

Genome-wide identification of QTL for seed yield and yield-related traits and construction of a high-density consensus map for QTL comparison in Brassica napus

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Weiguo eZhao

2016-01-01

Full Text Available Seed yield (SY is the most important trait in rapeseed, which was determined by multiple seed yield-related traits (SYRTs and also easily subject to environmental influence. Lots of quantitative trait loci (QTL for SY and SYRTs were reported in Brassica napus. However, no studies have focused on SY and seven agronomic traits affecting SY simultaneous. Genome-wide QTL analysis for SY and seven SYRTs in eight environments was conducted in a doubled haploid population containing 348 lines. Totally, 18 and 208 QTLs for SY and SYRTs were observed, respectively, and then these QTLs were integrated into 144 consensus QTLs by a meta-analysis. Three major QTLs for SY were observed, including cqSY-C6-2 and cqSY-C6-3 that expressed stably in winter cultivation area for three years and cqSY-A2-2 only expressed in spring rapeseed area. Trait-by-trait meta-analysis revealed that the 144 consensus QTLs were integrated into 72 pleiotropic unique QTLs. Among them, all the unique QTLs affected SY, except for uq-A6-1, including uq.A2-3, uq.C1-2, uq.C1-3, uq.C6-1, uq.C6-5 and uq.C6-6 could also affect more than two SYRTs. According to high density consensus map construction and QTL comparison from literature, 36 QTLs from five populations were co-localized with QTLs identified in this study. In addition, 13 orthologs genes were observed, including five each genes for SY and SW, one each gene for BY, BH and PH, respectively. The genomic information of these QTLs would be valuable in hybrid cultivar breeding, and be helpful to analyze QTL expression in different environments.

Serotonin 2A and 2C receptor biosynthesis in the rodent striatum during postnatal development: mRNA expression and functional linkage to neuropeptide gene regulation.

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Basura, G J; Walker, P D

2000-11-01

The present study was designed to determine if there are region-specific differences in serotonin (5-HT) neurotransmission and 5-HT receptor expression that may limit the stimulatory effects of the 5-HT releaser p-chloroamphetamine (pCA) on striatal neuropeptide gene expression to the posterior striatum (P-STR) during postnatal maturation. Sprague-Dawley rat brains from postnatal days (PND) 1-35 were processed for 5-HT(2A) and 5-HT(2C) receptor mRNA expression by in situ hybridization and monoamine analysis by HPLC. Within the P-STR, 5-HT(2A) receptor mRNA expression reached young adult (PND 35) levels by PND 3, while levels in the A-STR were significantly less (range: 1.43 +/- 0.219-6. 36 +/- 0.478) than P-STR (5.36 +/- 0.854-12.11 +/- 1.08) at each respective age throughout the time course. 5-HT(2C) receptor mRNA expression reached young adult levels at PND 7 in the A-STR and by PND 3 in the P-STR. At each PND age 5-HT(2C) receptor mRNA levels within the P-STR were significantly less (6.23 +/- 1.02-12.32 +/- 0.427) than the A-STR (7.31 +/- 1.65-26.84 +/- 2.24). 5-HT content increased across the developmental time course within the P-STR (5.01 +/- 0.327-15.7 +/- 1.03 ng/mg protein) and A-STR (2.97 +/- 0. 223-11.2 +/- 0.701 ng/mg protein). Four hours following injection (i. p.) of pCA (10 mg/kg), preprotachykinin (PPT) mRNA levels increased 89% in the P-STR but not the anterior (A-STR) striatum of the 3-week-old rat, which were prevented by preinjection (30 min, i.p.) of the 5-HT(2) receptor antagonist ritanserin (1 mg/kg). Together, these data suggest that faster maturity of 5-HT(2A) receptor expression in the P-STR may be sufficient to convey the region-specific acute stimulatory effects of pCA on PPT mRNA transcription in the developing rodent striatum. These results provide further evidence that the influence of 5-HT on neuropeptide gene expression is far stronger in caudal vs. rostral striatal regions during postnatal development. Copyright 2000 Wiley

PET study of the [{sup 11}C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow

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Hassoun, Wadad; Ginovart, Nathalie; Zimmer, Luc; Gualda, Veronique; Bonnefoi, Frederic [CERMEP, Lyon (France); Le Cavorsin, Marion; Leviel, Vincent [CNRS UMR5123, Villeurbanne (France)

2003-01-01

Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [{sup 11}C]raclopride (BP{sub raclo}), a radioligand with good specificity for dopamine (DA) receptors of the D{sub 2} type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg{sup -1} h{sup -1}; i.m.) and anaesthetised with halothane (1.5%). Non-specific binding was evaluated in the cerebellum. In the striatum of both sides, the BP{sub raclo} was unmodified by ketamine anaesthesia when compared with awake animals. In contrast, a large increase in BP{sub raclo} was observed under halothane anaesthesia. The non-specific binding of [{sup 11}C]raclopride, evaluated in the cerebellum, was also unchanged under ketamine anaesthesia but greatly increased under halothane anaesthesia. To evaluate whether changes in the cerebral blood flow (CBF) resulting from the different experimental situations could be at the root of these discrepancies, injections of [{sup 15}O]H{sub 2}O were performed; measurements revealed a drastically increased CBF under halothane anaesthesia and a slight enhancement under ketamine anaesthesia, when compared with the waking state. These results are the first to be obtained on this topic in awake cats, and show that the BP{sub raclo} is greatly dependent on alterations in the CBF. (orig.)

Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

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Luan, Yanan; Ren, Xiangpeng; Zheng, Wu; Zeng, Zhenhai; Guo, Yingzi; Hou, Zhidong; Guo, Wei; Chen, Xingjun; Li, Fei; Chen, Jiang-Fan

2018-01-01

Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

Age- and sex-dependence of dopamine release and capacity for recovery identified in the dorsal striatum of C57/Bl6J mice.

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Emma Arvidsson

Full Text Available The dorsal striatum is the main input structure of the basal ganglia and the major target area of dopaminergic projections originating in the substantia nigra pars compacta. Heavily involved in the regulation of voluntary movement and habit formation, this structure is of strong importance in Parkinson's disease, obsessive-compulsive disorder, Tourette's syndrome and addiction. The C57/Bl6J mouse strain, the most commonly used strain in preclinical research today, is frequently used as a model organism for analysis of dopaminergic parameters implicated in human pathophysiology. Several components of the dopamine system have been shown to vary with age and sex, however knowledge of the contribution of these factors for dopamine release kinetics in the C57/Bl6J mouse strain is lacking. In the present study, we used an intracranial KCl-stimulation challenge paradigm to provoke release from dopaminergic terminals in the dorsal striatum of anaesthetized C57/Bl6J mice. By high-speed in vivo chronoamperometric recordings, we analyzed DA release parameters in male and female mice of two different ages. Our experiments demonstrate elevated DA amplitudes in adult compared to young mice of both sexes and higher DA amplitudes in females compared to males at both ages. Adult mice exhibited higher recovery capabilities after repeated stimulation than did young mice and also showed a lower variability in the kinetic parameters trise and t80 between stimulations. These results identified age- and sex- dimorphisms in DA release parameters and point to the importance of taking these dimorphisms into account when utilizing the C57/Bl6J mouse strain as model for neurological and neuropsychiatric disorders.

Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

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Yu, Yan; Zeng, Changchun; Shu, Siyun; Liu, Xuemei; Li, Chuhua

2014-01-01

Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal division of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neurokinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Independent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addition to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum. PMID:25206901

Distinct Reward Properties are Encoded via Corticostriatal Interactions.

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Smith, David V; Rigney, Anastasia E; Delgado, Mauricio R

2016-02-02

The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior.

High motivation for exercise is associated with altered chromatin regulators of monoamine receptor gene expression in the striatum of selectively bred mice.

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Saul, M C; Majdak, P; Perez, S; Reilly, M; Garland, T; Rhodes, J S

2017-03-01

Although exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days. Among these genes were Htr1b, a serotonin receptor subunit and Slc38a2, a marker for both glutamatergic and γ-aminobutyric acid (GABA)-ergic signaling. System analysis of the raw results found enrichment of transcriptional regulation and kinase genes. Further, we identified a splice variant affecting the Wnt-related Golgi signaling gene Tmed5. Using coexpression network analysis, we found a cluster of interrelated coexpression modules with relationships to running behavior. From these modules, we built a network correlated with running that predicts a mechanistic relationship between transcriptional regulation by nucleosome structure and Htr1b expression. The Library of Integrated Network-Based Cellular Signatures identified the protein kinase C δ inhibitor, rottlerin, the tyrosine kinase inhibitor, Linifanib and the delta-opioid receptor antagonist 7-benzylidenenaltrexone as potential compounds for increasing the motivation to run. Taken together, our findings support a neurobiological framework of exercise motivation where chromatin state leads to differences in dopamine signaling through modulation of both the primary neurotransmitters glutamate and GABA, and by neuromodulators such as serotonin. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Genetic dissection of grain traits in Yamadanishiki, an excellent sake-brewing rice cultivar.

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Okada, Satoshi; Suehiro, Miki; Ebana, Kaworu; Hori, Kiyosumi; Onogi, Akio; Iwata, Hiroyoshi; Yamasaki, Masanori

2017-12-01

The grain traits of Yamadanishiki, an excellent sake-brewing rice cultivar in Japan, are governed by multiple QTLs, namely, a total of 42 QTLs including six major QTLs. Japanese rice wine (sake) is produced using brewing rice (Oryza sativa L.) that carries traits desirable for sake-brewing, such as a larger grain size and higher white-core expression rate (WCE) compared to cooking rice cultivars. However, the genetic basis for these traits in brewing rice cultivars is still unclear. We performed analyses of quantitative trait locus (QTL) of grain and days to heading over 3 years on populations derived from crosses between Koshihikari, a cooking rice, and Yamadanishiki, an excellent sake-brewing rice. A total of 42 QTLs were detected for the grain traits, and the Yamadanishiki alleles at 16 QTLs contributed to larger grain size. Two major QTLs essential for regulating both 100-grain weight (GWt) and grain width (GWh) were harbored in the same regions on chromosomes 5 and 10. An interaction was noted between the environment and the QTL associated with WCE on chromosome 6, which was detected in two of 3 years. In addition, two QTLs for WCE on chromosomes 3 and 10 overlapped with the QTLs for GWt and GWh, suggesting that QTLs associated with grain size also play an important role in the formation of white-core. Despite differences in the rate of grain growth in both Koshihikari and Yamadanishiki across 2 years, the WCE in Yamadanishiki remained consistent, thus demonstrating that the formation of white-core does not depend on grain filling speed. These data can be informative for programs involved in breeding better cooking and brewing rice cultivars.

Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption.

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Lauren A Vanderlinden

Full Text Available To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA. Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL with a genomic region that regulates alcohol consumption (bQTL. To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we compared candidate coexpression modules from whole brain gene expression data (gathered with Affymetrix 430 v2 arrays in the Colorado laboratories and from gene expression data from 6 brain regions (nucleus accumbens (NA; prefrontal cortex (PFC; ventral tegmental area (VTA; striatum (ST; hippocampus (HP; cerebellum (CB available from GeneNetwork. The candidate modules were used to construct candidate eigengene networks across brain regions, resulting in three "meta-modules", composed of candidate modules from two or more brain regions (NA, PFC, ST, VTA and whole brain. To mitigate the potential influence of chromosomal location of transcripts and cis-eQTLs in linkage disequilibrium, we calculated a semi-partial correlation of the transcripts in the meta-modules with alcohol consumption conditional on the transcripts' cis-eQTLs. The function of transcripts that retained the correlation with the phenotype after correction for the strong genetic influence, implicates processes of protein metabolism in the ER and Golgi as influencing susceptibility to variation in alcohol consumption. Integration of these data with human GWAS provides further information on the function of polymorphisms associated with alcohol-related traits.

Regulatory network of secondary metabolism in Brassica rapa: insight into the glucosinolate pathway.

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Dunia Pino Del Carpio

Full Text Available Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical genomics approach to identify regulatory genes for six biosynthetic pathways of health-related phytochemicals, i.e carotenoids, tocopherols, folates, glucosinolates, flavonoids and phenylpropanoids. Leaves from six weeks-old plants of a Brassica rapa doubled haploid population, consisting of 92 genotypes, were profiled for their secondary metabolite composition, using both targeted and LC-MS-based untargeted metabolomics approaches. Furthermore, the same population was profiled for transcript variation using a microarray containing EST sequences mainly derived from three Brassica species: B. napus, B. rapa and B. oleracea. The biochemical pathway analysis was based on the network analyses of both metabolite QTLs (mQTLs and transcript QTLs (eQTLs. Co-localization of mQTLs and eQTLs lead to the identification of candidate regulatory genes involved in the biosynthesis of carotenoids, tocopherols and glucosinolates. We subsequently focused on the well-characterized glucosinolate pathway and revealed two hotspots of co-localization of eQTLs with mQTLs in linkage groups A03 and A09. Our results indicate that such a large-scale genetical genomics approach combining transcriptomics and metabolomics data can provide new insights into the genetic regulation of metabolite composition of Brassica vegetables.

Unconditional and Conditional QTL Mapping for Tiller Numbers at Various Stages with Single Segment Substitution Lines in Rice (Oryza sativa L.)

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ZHAO Fang-ming; LIU Gui-fu; ZHU Hai-tao; DING Xiao-hua; ZENG Rui-zhen; ZHANG Ze-min; LI Wen-tao; ZHANG Gui-quan

2008-01-01

Tiller is one of the most important agronomic traits which influences quantity and quality of effective panicles and finally influences yield in rice.It is important to understand "static" and "dynamic" information of the QTLs for tillers in rice.This work was the first time to simultaneously map unconditional and conditional QTLs for tiller numbers at various stages by using single segment substitution lines in rice.Fourteen QTLs for tiller number,distributing on the corresponding substitution segments of chromosomes 1,2,3,4,6,7 and 8 were detected.Both the number and the effect of the QTLs for tiller number were various at different stages,from 6 to 9 in the number and from 1.49 to 3.49 in the effect,respectively. Tiller number QTLs expressed in a time order,mainly detected at three stages of 0-7d,14-21d and 35-42d after transplanting with 6 positive,9 random and 6 negative expressing QTLs,respectively.Each of the QTLs expressed one time at least during the whole duration of rice.The tiller number at a specific stage was determined by sum of QTL effects estimated by the unconditional method,while the increasing or decreasing number in a given time interval was controlled by the total of QTL effects estimated by the conditional method.These results demonstrated that it is highly effective and accurate for mapping of the QTLs by using single segment substitution lines and the conditional analysis methodology.

High Density Linkage Map Construction and QTL Detection for Three Silique-Related Traits in Orychophragmus violaceus Derived Brassica napus Population

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Yi Yang

2017-09-01

Full Text Available Seeds per silique (SS, seed weight (SW, and silique length (SL are important determinant traits of seed yield potential in rapeseed (Brassica napus L., and are controlled by naturally occurring quantitative trait loci (QTLs. Mapping QTLs to narrow chromosomal regions provides an effective means of characterizing the genetic basis of these complex traits. Orychophragmus violaceus is a crucifer with long siliques, many SS, and heavy seeds. A novel B. napus introgression line with many SS was previously selected from multiple crosses (B. rapa ssp. chinesis × O. violaceus × B. napus. In present study, a doubled haploid (DH population with 167 lines was established from a cross between the introgression line and a line with far fewer SS, in order to detect QTLs for silique-related traits. By screening with a Brassica 60K single nucleotide polymorphism (SNP array, a high-density linkage map consisting of 1,153 bins and spanning a cumulative length of 2,209.1 cM was constructed, using 12,602 high-quality polymorphic SNPs in the DH population. The average recombination bin densities of the A and C subgenomes were 1.7 and 2.4 cM, respectively. 45 QTLs were identified for the three traits in all, which explained 4.0–34.4% of the total phenotypic variation; 20 of them were integrated into three unique QTLs by meta-analysis. These unique QTLs revealed a significant positive correlation between SS and SL and a significant negative correlation between SW and SS, and were mapped onto the linkage groups A05, C08, and C09. A trait-by-trait meta-analysis revealed eight, four, and seven consensus QTLs for SS, SW, and SL, respectively, and five major QTLs (cqSS.A09b, cqSS.C09, cqSW.A05, cqSW.C09, and cqSL.C09 were identified. Five, three, and four QTLs for SS, SW, and SL, respectively, might be novel QTLs because of the existence of alien genetic loci for these traits in the alien introgression. Thirty-eight candidate genes underlying nine QTLs for silique

Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster.

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Kurmangaliyev, Yerbol Z; Ali, Sammi; Nuzhdin, Sergey V

2015-12-12

RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. Here we explore natural genetic variation affecting editing levels of particular sites in 81 natural strains of Drosophila melanogaster. The analysis of associations between editing levels and single-nucleotide polymorphisms allows us to map putative cis-regulatory regions affecting editing of 16 A-to-I editing sites (cis-RNA editing quantitative trait loci or cis-edQTLs, P < 10(-8)). The observed changes in editing levels are validated by independent molecular technique. All identified regulatory variants are located in close proximity of modulated editing sites. Moreover, colocalized editing sites are often regulated by same loci. Similar to expression and splicing QTL studies, the characterization of edQTLs will greatly expand our understanding of cis-regulatory evolution of gene expression. Copyright © 2016 Kurmangaliyev et al.

Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster

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Yerbol Z. Kurmangaliyev

2016-02-01

Full Text Available RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific targets. Here we explore natural genetic variation affecting editing levels of particular sites in 81 natural strains of Drosophila melanogaster. The analysis of associations between editing levels and single-nucleotide polymorphisms allows us to map putative cis-regulatory regions affecting editing of 16 A-to-I editing sites (cis-RNA editing quantitative trait loci or cis-edQTLs, P < 10−8. The observed changes in editing levels are validated by independent molecular technique. All identified regulatory variants are located in close proximity of modulated editing sites. Moreover, colocalized editing sites are often regulated by same loci. Similar to expression and splicing QTL studies, the characterization of edQTLs will greatly expand our understanding of cis-regulatory evolution of gene expression.

Prioritizing quantitative trait loci for root system architecture in tetraploid wheat.

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Maccaferri, Marco; El-Feki, Walid; Nazemi, Ghasemali; Salvi, Silvio; Canè, Maria Angela; Colalongo, Maria Chiara; Stefanelli, Sandra; Tuberosa, Roberto

2016-02-01

Optimization of root system architecture (RSA) traits is an important objective for modern wheat breeding. Linkage and association mapping for RSA in two recombinant inbred line populations and one association mapping panel of 183 elite durum wheat (Triticum turgidum L. var. durum Desf.) accessions evaluated as seedlings grown on filter paper/polycarbonate screening plates revealed 20 clusters of quantitative trait loci (QTLs) for root length and number, as well as 30 QTLs for root growth angle (RGA). Divergent RGA phenotypes observed by seminal root screening were validated by root phenotyping of field-grown adult plants. QTLs were mapped on a high-density tetraploid consensus map based on transcript-associated Illumina 90K single nucleotide polymorphisms (SNPs) developed for bread and durum wheat, thus allowing for an accurate cross-referencing of RSA QTLs between durum and bread wheat. Among the main QTL clusters for root length and number highlighted in this study, 15 overlapped with QTLs for multiple RSA traits reported in bread wheat, while out of 30 QTLs for RGA, only six showed co-location with previously reported QTLs in wheat. Based on their relative additive effects/significance, allelic distribution in the association mapping panel, and co-location with QTLs for grain weight and grain yield, the RSA QTLs have been prioritized in terms of breeding value. Three major QTL clusters for root length and number (RSA_QTL_cluster_5#, RSA_QTL_cluster_6#, and RSA_QTL_cluster_12#) and nine RGA QTL clusters (QRGA.ubo-2A.1, QRGA.ubo-2A.3, QRGA.ubo-2B.2/2B.3, QRGA.ubo-4B.4, QRGA.ubo-6A.1, QRGA.ubo-6A.2, QRGA.ubo-7A.1, QRGA.ubo-7A.2, and QRGA.ubo-7B) appear particularly valuable for further characterization towards a possible implementation of breeding applications in marker-assisted selection and/or cloning of the causal genes underlying the QTLs. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum.

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Faro, Lilian R F; Ferreira Nunes, Brenda V; Alfonso, Miguel; Ferreira, Vania M; Durán, Rafael

2013-09-15

The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5. Administration of GLA to CNQX (500μM) pretreated animals produced an effect that was not significantly different from the one produced in animals not pretreated with CNQX. On the other hand, administration of GLA to l-NAME (100μM) or 7-NI (100μM) pretreated animals, produced increases in dopamine overflow that were ∼80% and ∼75% smaller than those observed in animals not pretreated with these inhibitors. In summary, GLA appears to act, at least in part, through an overstimulation of NMDA (and not AMPA/kainate) receptors with possible NO production to induce in vivo dopamine release. Administration of NMDA receptor antagonists and NOS inhibitors partially blocks the release of dopamine from rat striatum. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder.

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Holz, Nathalie E; Boecker-Schlier, Regina; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-02-01

Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

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Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

SNP-based linkage mapping for validation of QTLs for resistance to ascochyta blight in lentil

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Shimna Sudheesh

2016-11-01

Full Text Available Lentil (Lens culinaris Medik. is a self-pollinating, diploid, annual, cool-season, food legume crop that is cultivated throughout the world. Ascochyta blight (AB, caused by Ascochyta lentis Vassilievsky, is an economically important and widespread disease of lentil. Development of cultivars with high levels of durable resistance provides an environmentally acceptable and economically feasible method for AB control. A detailed understanding of the genetic basis of AB resistance is hence highly desirable, in order to obtain insight into the number and influence of resistance genes. Genetic linkage maps based on single nucleotide polymorphisms (SNP and simple sequence repeat (SSR markers have been developed from three recombinant inbred line (RIL populations. The IH x NF map contained 460 loci across 1461.6 cM, while the IH x DIG map contained 329 loci across 1302.5 cM and the third map, NF x DIG contained 330 loci across 1914.1 cM. Data from these maps were combined with a map from a previously published study through use of bridging markers to generate a consensus linkage map containing 689 loci distributed across 7 linkage groups (LGs, with a cumulative length of 2429.61 cM at an average density of one marker per 3.5 cM. Trait dissection of AB resistance was performed for the RIL populations, identifying totals of two and three quantitative trait loci (QTLs explaining 52% and 69% of phenotypic variation for resistance to infection in the IH x DIG and IH x NF populations, respectively. Presence of common markers in the vicinity of the AB_IH1- and AB_IH2.1/AB_IH2.2-containing regions on both maps supports the inference that a common genomic region is responsible for conferring resistance and is associated with the resistant parent, Indianhead. The third QTL was derived from Northfield. Evaluation of markers associated with AB resistance across a diverse lentil germplasm panel revealed that the identity of alleles associated with AB_IH1 predicted

Exercise and diet affect quantitative trait loci for body weight and composition traits in an advanced intercross population of mice

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Kelly, Scott A.; Hua, Kunjie; Pomp, Daniel

2012-01-01

Driven by the recent obesity epidemic, interest in understanding the complex genetic and environmental basis of body weight and composition is great. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G10 advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study and also measured for four exercise traits prior to death, allowing us to test for pre- and postexercise QTLs as well as QTL-by-diet and QTL-by-exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G4) generation. For those replicated QTLs, the confidence intervals were reduced from an average of 19 Mb in the G4 to 8 Mb in the G10. Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen. PMID:23048196

Inhibition of transcription and translation in the striatum after memory reactivation: Lack of evidence of reconsolidation.

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Prado-Alcalá, Roberto A; Medina, Andrea Cristina; Bello-Medina, Paola C; Quirarte, Gina L

2017-07-01

It has been found that interference with neural activity after a consolidated memory is retrieved produces an amnestic state; this has been taken has indicative of destabilization of the memory trace that would have been produced by a process of reconsolidation (allowing for maintenance of the original trace). However, a growing body of evidence shows that this is not a reliable effect, and that it is dependent upon some experimental conditions, such as the age of the memory, memory reactivation procedures, the predictability of the reactivation stimulus, and strength of training. In some instances, where post-retrieval treatments induce a retention deficit (which would be suggestive of interference with reconsolidation), memory is rescued by simple passing of time or by repeated retention tests. We now report that post-training and post-retrieval inhibition of transcription and translation in dorsal striatum, a structure where both of these manipulations have not been studied, produce interference with consolidation and a transitory retention deficit, respectively. These results do not give support to the reconsolidation hypothesis and lead to the conclusion that the post-activation deficiencies are due to interference with retrieval of information. Copyright © 2016 Elsevier Inc. All rights reserved.

Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

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Torres, Carmen; Glueck, Amanda C; Conrad, Shannon E; Morón, Ignacio; Papini, Mauricio R

2016-09-22

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

QTL underlying some agronomic traits in barley detected by SNP markers.

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Wang, Jibin; Sun, Genlou; Ren, Xifeng; Li, Chengdao; Liu, Lipan; Wang, Qifei; Du, Binbin; Sun, Dongfa

2016-07-07

Increasing the yield of barley (Hordeum vulgare L.) is a main breeding goal in developing barley cultivars. A high density genetic linkage map containing 1894 SNP and 68 SSR markers covering 1375.8 cM was constructed and used for mapping quantitative traits. A late-generation double haploid population (DH) derived from the Huaai 11 × Huadamai 6 cross was used to identify QTLs and QTL × environment interactions for ten traits affecting grain yield including length of main spike (MSL), spikelet number on main spike (SMS), spikelet number per plant (SLP), grain number per plant (GP), grain weight per plant (GWP), grain number per spike (GS), thousand grain weight (TGW), grain weight per spike (GWS), spike density (SPD) and spike number per plant (SP). In single environment analysis using composite interval mapping (CIM), a total of 221 QTLs underlying the ten traits were detected in five consecutive years (2009-2013). The QTLs detected in each year were 50, 48, 41, 41 and 41 for the year 2009 to 2013. The QTLs associated with these traits were generally clustered on chromosome 2H, 4H and 7H. In multi-environment analysis, a total of 111 significant QTLs including 18 for MSL, 16 for SMS, 15 for SPD, 5 for SP, 4 for SLP, 14 for TGW, 5 for GP, 11 for GS, 8 for GWP, and 15 for GWS were detected in the five years. Most QTLs showed significant QTL × environment interactions (QEI), nine QTLs (qIMSL3-1, qIMSL4-1, qIMSL4-2, qIMSL6-1, qISMS7-1, qISPD2-7, qISPD7-1, qITGW3-1 and qIGWS4-3) were detected with minimal QEI effects and stable in different years. Among 111 QTLs,71 (63.40 %) QTLs were detected in both single and multiple environments. Three main QTL cluster regions associated with the 10 agronomic traits on chromosome 2H, 4H and 7H were detected. The QTLs for SMS, SLP, GP and GWP were located in the region near Vrs1 on chromosome 2H. The QTLs underlying SMS, SPD and SLP were clustered on chromosome 4H. On the terminal of chromosome 7H, there was a QTL

Central Bank independence

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Vasile DEDU

2012-08-01

Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

Genetic dissection of growth, wood basic density and gene expression in interspecific backcrosses of Eucalyptus grandis and E. urophylla

Science.gov (United States)

2012-01-01

Background F1 hybrid clones of Eucalyptus grandis and E. urophylla are widely grown for pulp and paper production in tropical and subtropical regions. Volume growth and wood quality are priority objectives in Eucalyptus tree improvement. The molecular basis of quantitative variation and trait expression in eucalypt hybrids, however, remains largely unknown. The recent availability of a draft genome sequence (http://www.phytozome.net) and genome-wide genotyping platforms, combined with high levels of genetic variation and high linkage disequilibrium in hybrid crosses, greatly facilitate the detection of quantitative trait loci (QTLs) as well as underlying candidate genes for growth and wood property traits. In this study, we used Diversity Arrays Technology markers to assess the genetic architecture of volume growth (diameter at breast height, DBH) and wood basic density in four-year-old progeny of an interspecific backcross pedigree of E. grandis and E. urophylla. In addition, we used Illumina RNA-Seq expression profiling in the E. urophylla backcross family to identify cis- and trans-acting polymorphisms (eQTLs) affecting transcript abundance of genes underlying QTLs for wood basic density. Results A total of five QTLs for DBH and 12 for wood basic density were identified in the two backcross families. Individual QTLs for DBH and wood basic density explained 3.1 to 12.2% of phenotypic variation. Candidate genes underlying QTLs for wood basic density on linkage groups 8 and 9 were found to share trans-acting eQTLs located on linkage groups 4 and 10, which in turn coincided with QTLs for wood basic density suggesting that these QTLs represent segregating components of an underlying transcriptional network. Conclusion This is the first demonstration of the use of next-generation expression profiling to quantify transcript abundance in a segregating tree population and identify candidate genes potentially affecting wood property variation. The QTLs identified in this

QTL mapping and epistatic interaction analysis in asparagus bean for several characterized and novel horticulturally important traits

Science.gov (United States)

2013-01-01

Background Asparagus bean (Vigna. unguiculata. ssp sesquipedalis) is a subspecies and special vegetable type of cowpea (Vigna. unguiculata L. Walp.) important in Asia. Genetic basis of horticulturally important traits of asparagus bean is still poorly understood, hindering the utilization of targeted, DNA marker-assisted breeding in this crop. Here we report the identification of quantitative trait loci (QTLs) and epistatic interactions for four horticultural traits, namely, days to first flowering (FLD), nodes to first flower (NFF), leaf senescence (LS) and pod number per plant (PN) using a recombinant inbred line (RIL) population of asparagus bean. Results A similar genetic mode of one major QTL plus a few minor QTLs was found to dominate each of the four traits, with the number of QTLs for individual traits ranging from three to four. These QTLs were distributed on 7 of the 11 chromosomes. Major QTLs for FLD, NFF and LS were co-localized on LG 11, indicative of tight linkage. Genome wide epistasis analysis detected two and one interactive locus pairs that significantly affect FLD and LS, respectively, and the epistatic QTLs for FLD appeared to work in different ways. Synteny based comparison of QTL locations revealed conservation of chromosome regions controlling these traits in related legume crops. Conclusion Major, minor, and epistatic QTLs were found to contribute to the inheritance of the FLD, NFF, LS, and PN. Positions of many of these QTLs are conserved among closely related legume species, indicating common mechanisms they share. To our best knowledge, this is the first QTL mapping report using an asparagus bean × asparagus bean intervarietal population and provides marker-trait associations for marker-assisted approaches to selection. PMID:23375055

Linkage Map Construction and QTL Analysis of Fruit Traits in Melon (Cucumis melo L.) Based on CAPS Markers

International Nuclear Information System (INIS)

Baloch, A. M.; Liu, S.; Wang, X.; Luan, F.; Baloch, A. W.; Baloch, M. J.

2016-01-01

In the current experiment, the quantitative trait loci (QTL) analysis was done by composite interval mapping method to detect QTLs in edge, central parts and fruit shape of melon. In this context, 235 F/sub 2/ populations along with their parents were evaluated for fruit size, shape and color under replicated trail at Horticulture Experimental Station of Northeast Agricultural University, Harbin, China, during the growing year 2014. Moreover, 96 pairs of CAPS markers were used to construct a linkage map using F/sub 2/ population that was derived from the cross between two contrasting parents (MR-1 and Topmark). The total length of linkage map was found to be 4984.1cM with an average of 51.9177 cM between the markers. In a total, we detected ten QTLs, in which one was major, while others were minor. Five QTLs were detected in the edge part of melon fruit and three QTLs were detected in central parts of melon and all were considered as Brix content. Two QTLs were related with fruit shape. Our present genetic and QTLs mapping would be proved useful in plant breeding programs for the improvement of economically important horticultural traits. (author)

Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea Using QTL-seq Reveals Markers for Marker-Assisted Selection

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Josh Clevenger

2018-02-01

Full Text Available Late leaf spot (LLS; Cercosporidium personatum is a major fungal disease of cultivated peanut (Arachis hypogaea. A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools.Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping.

MDMA-evoked changes in the binding of dopamine D(2) receptor ligands in striatum of rats with unilateral serotonin depletion

DEFF Research Database (Denmark)

Ostergaard, Søren Dinesen; Alstrup, Aage Kristian Olsen; Gramsbergen, Jan Bert

2010-01-01

We earlier reported an anomalous 50% decrease in [(11)C]N-methylspiperone ([(11)C]NMSP) binding to dopamine D(2)-like receptors in living pig striatum after challenge with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), suggesting either (1) a species peculiarity in the vulnerability...... lesions, later verified by [(125)I]RTI-55 autoradiography. Baseline [(11)C]NMSP microPET recordings were followed by either saline or MDMA-HCl (4 mg/kg) injections (i.v.), and a second [(11)C]NMSP recording, culminating with injection of [(3)H]raclopride for autoradiography ex vivo. Neither MDMA......-challenge nor serotonin lesion had any detectable effect on [(11)C]NMSP binding. In contrast, MDMA challenge increased receptor occupancy by [(3)H]raclopride ex vivo (relative to the B(max) in vitro) from 8% to 12%, and doubled the free ligand concentration in cerebral cortex, apparently by blocking hepatic CYP...

Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

DEFF Research Database (Denmark)

Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

2011-01-01

It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.

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Markus Drag

Full Text Available Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS were slaughtered at ~100 kg. Gene expression profiles were obtained by RNA-Seq, and genotype data were obtained by an Illumina 60K Porcine SNP chip. Following quality control and filtering, 10,545 and 12,731 genes from liver and testis were included in the eQTL analysis, together with 20,827 SNP variants. A total of 205 and 109 single-tissue eQTLs associated with 102 and 58 unique genes were identified in liver and testis, respectively. By employing a multivariate Bayesian hierarchical model, 26 eQTLs were identified as significant multi-tissue eQTLs. The highest densities of eQTLs were found on pig chromosomes SSC12, SSC1, SSC13, SSC9 and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits curated by the Animal Genome PigQTL database to be significantly overlapped by the genomic coordinates of cis-acting eQTLs. Finally, a subset of 35 cis-acting eQTLs overlapped with known boar taint QTL traits. These eQTLs could be useful in the development of a DNA test for boar taint but careful monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection.

Sequentially switching cell assemblies in random inhibitory networks of spiking neurons in the striatum.

Science.gov (United States)

Ponzi, Adam; Wickens, Jeff

2010-04-28

The striatum is composed of GABAergic medium spiny neurons with inhibitory collaterals forming a sparse random asymmetric network and receiving an excitatory glutamatergic cortical projection. Because the inhibitory collaterals are sparse and weak, their role in striatal network dynamics is puzzling. However, here we show by simulation of a striatal inhibitory network model composed of spiking neurons that cells form assemblies that fire in sequential coherent episodes and display complex identity-temporal spiking patterns even when cortical excitation is simply constant or fluctuating noisily. Strongly correlated large-scale firing rate fluctuations on slow behaviorally relevant timescales of hundreds of milliseconds are shown by members of the same assembly whereas members of different assemblies show strong negative correlation, and we show how randomly connected spiking networks can generate this activity. Cells display highly irregular spiking with high coefficients of variation, broadly distributed low firing rates, and interspike interval distributions that are consistent with exponentially tailed power laws. Although firing rates vary coherently on slow timescales, precise spiking synchronization is absent in general. Our model only requires the minimal but striatally realistic assumptions of sparse to intermediate random connectivity, weak inhibitory synapses, and sufficient cortical excitation so that some cells are depolarized above the firing threshold during up states. Our results are in good qualitative agreement with experimental studies, consistent with recently determined striatal anatomy and physiology, and support a new view of endogenously generated metastable state switching dynamics of the striatal network underlying its information processing operations.

Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

Science.gov (United States)

Goodman, J; Leong, K-C; Packard, M G

2015-12-17

Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

Dopamine transporter gene variation modulates activation of striatum in youth with ADHD.

Science.gov (United States)

Bédard, Anne-Claude; Schulz, Kurt P; Cook, Edwin H; Fan, Jin; Clerkin, Suzanne M; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

2010-11-15

Polymorphisms in the 3'UTR variable number tandem repeat (VNTR) of exon 15 of the dopamine transporter gene (DAT1) have been linked to attention-deficit hyperactivity disorder (ADHD); moreover, variability in DAT1 3'UTR genotype may contribute to both heterogeneity of the ADHD phenotype and differences in response to stimulant medications. The impact of this VNTR on neuronal function in individuals with ADHD remains unclear despite evidence that the polymorphisms influence dopamine transporter expression. Thus, we used event-related functional magnetic resonance imaging to examine the impact of DAT1 3'UTR genotype on brain activation during response inhibition in unmedicated children and adolescents with ADHD. Twenty-one youth with ADHD who were homozygous for the 10-repeat (10R) allele of the DAT1 3'UTR and 12 youth who were carriers of the 9-repeat (9R) allele were scanned while they performed a Go/No-Go task. Response inhibition was modeled by contrasting activation during correct No-Go trials versus correct Go trials. Participants who were homozygous for the DAT1 3'UTR 10R allele and those who had a single 9R allele did not differ on percent of trials with successful inhibition, which was the primary measure of inhibitory control. Yet, youth with the DAT1 3'UTR 10R/10R genotype had significantly greater inhibitory control-related activation than those with one 9R allele in the left striatum, right dorsal premotor cortex, and bilaterally in the temporoparietal cortical junction. These findings provide preliminary evidence that neural activity related to inhibitory control may differ as a function of DAT1 3'UTR genotype in youth with ADHD. Copyright 2009 Elsevier Inc. All rights reserved.

RFLP-facilitated investigation of the quantitative resistance of rice to brown planthopper ( Nilaparvata lugens).

Science.gov (United States)

Xu, X. F.; Mei, H. W.; Luo, L. J.; Cheng, X. N.; Li, Z. K.

2002-02-01

Quantitative trait loci (QTLs), conferring quantitative resistance to rice brown planthopper (BPH), were investigated using 160 F(11) recombinant inbred lines (RILs) from the Lemont/Teqing cross, a complete RFLP map, and replicated phenotyping of seedbox inoculation. The paternal indica parent, Teqing, was more-resistant to BPH than the maternal japonica parent, Lemont. The RILs showed transgressive segregation for resistance to BPH. Seven main-effect QTLs and many epistatic QTL pairs were identified and mapped on the 12 rice chromosomes. Collectively, the main-effect and epistatic QTLs accounted for over 70% of the total variation in damage scores. Teqing has the resistance allele at four main-effect QTLs, and the Lemont allele resulted in resistance at the other three. Of the main-effect QTLs identified, QBphr5b was mapped to the vicinity of gl1, a major gene controlling leaf and stem pubescence. The Teqing allele controlling leaf and stem pubescence was associated with resistance, while the Lemont allele for glabrous stem and leaves was associated with susceptibility, indicating that this gene may have contributed to resistance through antixenosis. Similar to the reported BPH resistance genes, the other six detected main-effect QTLs were all mapped to regions where major disease resistance genes locate, suggesting they might have contributed either to antibiosis or tolerance. Our results indicated that marker-aided pyramiding of major resistance genes and QTLs should provide effective and stable control over this devastating pest.

Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

Science.gov (United States)

Acquas, E; Di Chiara, G

1999-11-03

The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

GSTpi expression in MPTP-induced dopaminergic neurodegeneration of C57BL/6 mouse midbrain and striatum.

Science.gov (United States)

Castro-Caldas, Margarida; Neves Carvalho, Andreia; Peixeiro, Isabel; Rodrigues, Elsa; Lechner, Maria Celeste; Gama, Maria João

2009-06-01

MPTP-induced dopaminergic neurotoxicity involves major biochemical processes such as oxidative stress and impaired energy metabolism, leading to a significant reduction in the number of nigrostriatal dopaminergic neurons. Glutathione S-transferase pi (GSTpi) is a phase II detoxifying enzyme that provides protection of cells from injury by toxic chemicals and products of oxidative stress. In humans, polymorphisms of GSTP1 affect substrate selectivity and stability increasing the susceptibility to parkinsonism-inducing effects of environmental toxins. Given the ability of MPTP to increase the levels of reactive oxygen species and the link between altered redox potential and the expression and activity of GSTpi, we investigated the effect of MPTP on GSTpi cellular concentration in an in vivo model of Parkinson's disease. The present study demonstrates that GSTpi is actively expressed in both substantia nigra pars compacta and striatum of C57BL/6 mice brain, mostly in oligodendrocytes and astrocytes. After systemic administration of MPTP, GSTpi expression is significantly increased in glial cells in the vicinity of dopaminergic neurons cell bodies and fibers. The results suggest that GSTpi expression may be part of the mechanism underlying the ability of glial cells to elicit protection against the mechanisms involved in MPTP-induced neuronal death.

Mapping of quantitative trait locus (QTLs that contribute to germination and early seedling drought tolerance in the interspecific cross Setaria italica×Setaria viridis.

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Lufeng Qie

Full Text Available Drought tolerance is an important breeding target for enhancing the yields of grain crop species in arid and semi-arid regions of the world. Two species of Setaria, domesticated foxtail millet (S. italica and its wild ancestor green foxtail (S. viridis are becoming widely adopted as models for functional genomics studies in the Panicoid grasses. In this study, the genomic regions controlling germination and early seedling drought tolerance in Setaria were identified using 190 F7 lines derived from a cross between Yugu1, a S. italica cultivar developed in China, and a wild S. viridis genotype collected from Uzbekistan. Quantitative trait loci were identified which contribute to a number of traits including promptness index, radical root length, coleoptile length and lateral root number at germinating stage and seedling survival rate was characterized by the ability of desiccated seedlings to revive after rehydration. A genetic map with 128 SSR markers which spans 1293.9 cM with an average of 14 markers per linkage group of the 9 linkage groups was constructed. A total of eighteen QTLs were detected which included nine that explained over 10% of the phenotypic variance for a given trait. Both the wild green foxtail genotype and the foxtail millet cultivar contributed the favorite alleles for traits detected in this trial, indicating that wild Setaria viridis populations may serve as a reservoir for novel stress tolerance alleles which could be employed in foxtail millet breeding.

Mapping of quantitative trait locus (QTLs) that contribute to germination and early seedling drought tolerance in the interspecific cross Setaria italica×Setaria viridis.

Science.gov (United States)

Qie, Lufeng; Jia, Guanqing; Zhang, Wenying; Schnable, James; Shang, Zhonglin; Li, Wei; Liu, Binhui; Li, Mingzhe; Chai, Yang; Zhi, Hui; Diao, Xianmin

2014-01-01

Drought tolerance is an important breeding target for enhancing the yields of grain crop species in arid and semi-arid regions of the world. Two species of Setaria, domesticated foxtail millet (S. italica) and its wild ancestor green foxtail (S. viridis) are becoming widely adopted as models for functional genomics studies in the Panicoid grasses. In this study, the genomic regions controlling germination and early seedling drought tolerance in Setaria were identified using 190 F7 lines derived from a cross between Yugu1, a S. italica cultivar developed in China, and a wild S. viridis genotype collected from Uzbekistan. Quantitative trait loci were identified which contribute to a number of traits including promptness index, radical root length, coleoptile length and lateral root number at germinating stage and seedling survival rate was characterized by the ability of desiccated seedlings to revive after rehydration. A genetic map with 128 SSR markers which spans 1293.9 cM with an average of 14 markers per linkage group of the 9 linkage groups was constructed. A total of eighteen QTLs were detected which included nine that explained over 10% of the phenotypic variance for a given trait. Both the wild green foxtail genotype and the foxtail millet cultivar contributed the favorite alleles for traits detected in this trial, indicating that wild Setaria viridis populations may serve as a reservoir for novel stress tolerance alleles which could be employed in foxtail millet breeding.

Estradiol and song affect female zebra finch behavior independent of dopamine in the striatum

OpenAIRE

Svec, Lace A.; Lookingland, Keith J.; Wade, Juli

2009-01-01

Female songbirds display preferences for certain song characteristics, but the neural and hormonal mechanisms mediating these preferences are not fully clear. The present study sought to further explore the role of estradiol, as well as assess potential roles of dopaminergic systems, on behavioral responses to song. Adult female zebra finches were treated with estradiol and exposed to tutored or untutored song or silence. Behavior was quantified and neurochemistry of the nucleus accumbens and...

AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

International Nuclear Information System (INIS)

Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

2012-01-01

Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

Independence and Product Systems

OpenAIRE

Skeide, Michael

2003-01-01

Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

Impact of QTL minor allele frequency on genomic evaluation using real genotype data and simulated phenotypes in Japanese Black cattle.

Science.gov (United States)

Uemoto, Yoshinobu; Sasaki, Shinji; Kojima, Takatoshi; Sugimoto, Yoshikazu; Watanabe, Toshio

2015-11-19

Genetic variance that is not captured by single nucleotide polymorphisms (SNPs) is due to imperfect linkage disequilibrium (LD) between SNPs and quantitative trait loci (QTLs), and the extent of LD between SNPs and QTLs depends on different minor allele frequencies (MAF) between them. To evaluate the impact of MAF of QTLs on genomic evaluation, we performed a simulation study using real cattle genotype data. In total, 1368 Japanese Black cattle and 592,034 SNPs (Illumina BovineHD BeadChip) were used. We simulated phenotypes using real genotypes under different scenarios, varying the MAF categories, QTL heritability, number of QTLs, and distribution of QTL effect. After generating true breeding values and phenotypes, QTL heritability was estimated and the prediction accuracy of genomic estimated breeding value (GEBV) was assessed under different SNP densities, prediction models, and population size by a reference-test validation design. The extent of LD between SNPs and QTLs in this population was higher in the QTLs with high MAF than in those with low MAF. The effect of MAF of QTLs depended on the genetic architecture, evaluation strategy, and population size in genomic evaluation. In genetic architecture, genomic evaluation was affected by the MAF of QTLs combined with the QTL heritability and the distribution of QTL effect. The number of QTL was not affected on genomic evaluation if the number of QTL was more than 50. In the evaluation strategy, we showed that different SNP densities and prediction models affect the heritability estimation and genomic prediction and that this depends on the MAF of QTLs. In addition, accurate QTL heritability and GEBV were obtained using denser SNP information and the prediction model accounted for the SNPs with low and high MAFs. In population size, a large sample size is needed to increase the accuracy of GEBV. The MAF of QTL had an impact on heritability estimation and prediction accuracy. Most genetic variance can be captured

Organizing Independent Student Work

Directory of Open Access Journals (Sweden)

Zhadyra T. Zhumasheva

2015-03-01

Full Text Available This article addresses issues in organizing independent student work. The author defines the term “independence”, discusses the concepts of independent learner work and independent learner work under the guidance of an instructor, proposes a classification of assignments to be done independently, and provides methodological recommendations as to the organization of independent student work. The article discusses the need for turning the student from a passive consumer of knowledge into an active creator of it, capable of formulating a problem, analyzing the ways of solving it, coming up with an optimum outcome, and proving its correctness. The preparation of highly qualified human resources is the primary condition for boosting Kazakhstan’s competitiveness. Independent student work is a means of fostering the professional competence of future specialists. The primary form of self-education is independent work.

Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia.

Science.gov (United States)

Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Esslinger, Christine; Schilling, Claudia; Schirmbeck, Frederike; Englisch, Susanne; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

2014-07-01

Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetics of cryptic speciation within an Arctic mustard, Draba nivalis.

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A Lovisa S Gustafsson

Full Text Available Crossing experiments indicate that hybrid sterility barriers frequently have developed within diploid, circumpolar plant species of the genus Draba. To gain insight into the rapid evolution of postzygotic reproductive isolation in this system, we augmented the linkage map of one of these species, D. nivalis, and searched for quantitative trait loci (QTLs associated with reproductive isolation. The map adds 63 new dominant markers to a previously published dataset of 31 co-dominant microsatellites. These markers include 52 amplified fragment length polymorphisms (AFLPs and 11 sequence-specific amplified polymorphisms (SSAPs based on retrotransposon sequence. 22 markers displaying transmission ratio distortion were further included in the map. We resolved eight linkage groups with a total map length of 894 cM. Significant genotype-trait associations, or quantitative trait loci (QTL, were detected for reproductive phenotypes including pollen fertility (4 QTLs, seed set (3 QTLs, flowering time (3 QTLs and number of flowers (4 QTLs. Observed patterns of inheritance were consistent with the influence of both nuclear-nuclear interactions and chromosomal changes on these traits. All seed set QTLs and one pollen fertility QTL displayed underdominant effects suggestive of the involvement of chromosomal rearrangements in hybrid sterility. Interestingly, D. nivalis is predominantly self-fertilizing, which may facilitate the establishment of underdominant loci and contribute to reproductive isolation.

Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci.

Science.gov (United States)

Chauvet, Cristina; Crespo, Kimberley; Ménard, Annie; Roy, Julie; Deng, Alan Y

2013-11-15

Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP.