The Promising Future of Chia, Salvia hispanica L.

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Norlaily Mohd Ali

2012-01-01

Full Text Available With increasing public health awareness worldwide, demand for functional food with multiple health benefits has also increased. The use of medicinal food from folk medicine to prevent diseases such as diabetes, obesity, and cardiovascular problems is now gaining momentum among the public. Seed from Salvia hispanica L. or more commonly known as chia is a traditional food in central and southern America. Currently, it is widely consumed for various health benefits especially in maintaining healthy serum lipid level. This effect is contributed by the presence of phenolic acid and omega 3/6 oil in the chia seed. Although the presence of active ingredients in chia seed warrants its health benefits, however, the safety and efficacy of this medicinal food or natural product need to be validated by scientific research. In vivo and clinical studies on the safety and efficacy of chia seed are still limited. This paper covers the up-to-date research on the identified active ingredients, methods for oil extraction, and in vivo and human trials on the health benefit of chia seed, and its current market potential.

Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

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Aile evan Huijstee

2015-01-01

Full Text Available Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behaviour, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA. This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc and the prefrontal cortex (PFC, with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioural symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodelling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction.

Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

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van Huijstee, Aile N.; Mansvelder, Huibert D.

2015-01-01

Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behavior, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioral symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodeling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction. PMID:25653591

High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses.

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Gawlak, M; Górkiewicz, T; Gorlewicz, A; Konopacki, F A; Kaczmarek, L; Wilczynski, G M

2009-01-12

Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.

Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment.

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MacNamee, Sarah E; Liu, Kendra E; Gerhard, Stephan; Tran, Cathy T; Fetter, Richard D; Cardona, Albert; Tolbert, Leslie P; Oland, Lynne A

2016-07-01

Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron-glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic premotor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via excitatory amino acid transporter 1 (Eaat1), and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory postsynaptic currents in motor neurons. The neuronal synapses were always located within 1 μm of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters. J. Comp. Neurol. 524:1979-1998, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

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Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

2014-02-01

Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. © 2014 International Life Sciences Institute.

Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission

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Schousboe, A; Sarup, A; Bak, L K

2004-01-01

The fine tuning of both glutamatergic and GABAergic neurotransmission is to a large extent dependent upon optimal function of astrocytic transport processes. Thus, glutamate transport in astrocytes is mandatory to maintain extrasynaptic glutamate levels sufficiently low to prevent excitotoxic...... neuronal damage. In GABA synapses hyperactivity of astroglial GABA uptake may lead to diminished GABAergic inhibitory activity resulting in seizures. As a consequence of this the expression and functional activity of astrocytic glutamate and GABA transport is regulated in a number of ways...

An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

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Xinglong Gu

2016-01-01

Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

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Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

2016-05-01

Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

Stress-induced impairment of glutamatergic terminals ultrastructure: High vulnerability of medial prefrontal cortex and preventing action of desipramine

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Nava, N.; Popoli, M.; Musazzi, L.

2013-01-01

mediators, glucocorticoids, on brain volume and dendritic remodeling, in both humans and rodents. Nevertheless, few is still known on the structural changes exerted by behavioral stress on the features of glutamatergic synapses as sites of neuronal communication. Indeed, in excitatory synapses synaptic...... communication is driven by neurotransmitter which is stored, within the presynaptic terminal, in morphologically distinct pools of vesicles, namely the readily-releasable pool of vesicles (RRP), docked to the active zone and ready for release, and the reserve pool of vesicles. When neurotransmitter is released...

Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

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Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

2017-06-21

Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan. SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

The Tūqmāq and the Ming China: The Tūqmāq and the Chinese Relations during the Ming Period (1394–1456)

OpenAIRE

Kenzheakhmet N.

2017-01-01

Objective: Little is known about diplomatic relations between the Jūchīd Ulūs and Ming China (1368–1644), even though some evidence of early tributary trade relations exists. The first extant Chinese account about the country of Salai (Saray) dates to around 1394, when accounts of diplomatic exchange between the Ming court and the Jūchīd Ulūs began to appear in the Ming shilu (The Veritable Records of the Ming). Research materials: This article analyzes the Ming shilu in order to understan...

Witnessing stressful events induces glutamatergic synapse pathway alterations and gene set enrichment of positive EPSP regulation within the VTA of adult mice: An ontology based approach

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Brewer, Jacob S.

It is well known that exposure to severe stress increases the risk for developing mood disorders. Currently, the neurobiological and genetic mechanisms underlying the functional effects of psychological stress are poorly understood. Presenting a major obstacle to the study of psychological stress is the inability of current animal models of stress to distinguish between physical and psychological stressors. A novel paradigm recently developed by Warren et al., is able to tease apart the effects of physical and psychological stress in adult mice by allowing these mice to "witness," the social defeat of another mouse thus removing confounding variables associated with physical stressors. Using this 'witness' model of stress and RNA-Seq technology, the current study aims to study the genetic effects of psychological stress. After, witnessing the social defeat of another mouse, VTA tissue was extracted, sequenced, and analyzed for differential expression. Since genes often work together in complex networks, a pathway and gene ontology (GO) analysis was performed using data from the differential expression analysis. The pathway and GO analyzes revealed a perturbation of the glutamatergic synapse pathway and an enrichment of positive excitatory post-synaptic potential regulation. This is consistent with the excitatory synapse theory of depression. Together these findings demonstrate a dysregulation of the mesolimbic reward pathway at the gene level as a result of psychological stress potentially contributing to depressive like behaviors.

Development and sensory evaluation of yogurt with chia seeds

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Melina Vilela dos Santos

2017-11-01

Full Text Available The objective of this study was to develop and evaluate the sensory acceptance of yogurt formulations with chia seeds. After preparation of the formulations (A - Control, B - yogurt added of 2% of chia seeds, C - yoghurt added of 3% of chia seeds, microbiological and physicochemical analyzes were performed. Hedonic scales were used to verify the acceptance and the intention to purchase the elaborated formulations, as well as the Acceptability Index. The data of the acceptance and purchase intention tests were evaluated through Analysis of Variance (ANOVA, and later, Tukey’s Test was applied at a 5% probability. Yogurt formulations were within the standards required by Brazilian Legislation for microbiological and physicochemical analyzes. There was no significant difference (p > 0,05 between the 3 yoghurt formulations for the attributes of flavor, texture and overall impression. However, regarding the appearance attribute, the formulation with 3% chia (C seeds was less appreciated (p 0,05 regarding the average of the purchase intention notes for the 3 yogurt formulations. It was concluded that the yogurt formulations with chia seeds were adequate for the microbiological and physicochemical parameters during the storage period, besides obtaining a good sensorial acceptance, presenting itself as a healthier milk alternative for the consumers.

Nutritional composition in the chia seed and its processing properties on restructured ham-like products

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Yi Ding

2018-01-01

Full Text Available Low-fat meat products always have harder texture, lower juiciness, and worse flavor. Due to their higher water-holding, water absorption, and organic molecule absorption, chia seeds (CHIA have been applied in powders, nutrition bars, breads, and cookies. Hence, the objectives of this study were to: (1 analyze the nutritional compositions in CHIA; and (2 look for the possible application of CHIA on restructured ham-like products. CHIA has high amounts of α-linolenic acid, crude polysaccharides, and also contains essential amino acids, minerals, and polyphenols. Regarding processing properties of CHIA, a combination of CHIA and carrageenan (CA increased (p<0.05 production yield of restructured ham-like products. A scanning electron microscope observation indicated that CHIA and CA addition can assist an emulsification in this ham-like product. Addition of 0.5% CA and 1.0% CHIA in this ham-like product showed the similar overall acceptance as products with added fat. Following storage at 4°C, higher (p<0.05 purge and centrifugation losses, as well as hardness of this ham-like product can be improved by adding CHIA and CA. CHIA addition also resulted in lower (p<0.05 lipid and protein oxidation, especially a 1.0% addition. In summary, due to both nutritional addition and improvements on physicochemical and sensorial properties of restructured ham-like products, CHIA seeds have great potential on the development of healthy and good-quality meat products.

Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.

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Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B; Perrat, Paola N; Waddell, Scott

2016-03-16

Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Shaping inhibition: activity dependent structural plasticity of GABAergic synapses

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Carmen E Flores

2014-10-01

Full Text Available Inhibitory transmission through the neurotransmitter Ɣ-aminobutyric acid (GABA shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

ming-fa hsieh

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. MING-FA HSIEH. Articles written in Bulletin of Materials Science. Volume 40 Issue 6 October 2017 pp 1179-1187. Preparation, characterization of chitosan/bamboo charcoal/poly(methacrylate) composite beads · DOROTHY CAMINOS-PERUELO WEI-CHIEH WANG ...

The "Da Ming Hunyi Tu": Repurposing a Ming Map in Sino-African Diplomacy

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Alexander Akin

2016-12-01

Full Text Available In 2002, an exhibition at South Africa’s parliament included a reproduction of the Da Ming Hunyi Tu (Amalgamated map of the Great Ming, citing it as the earliest world map to depict the entire African continent. As part of its broader efforts to shape a narrative of long-standing and peaceful international relations with Africa, the People’s Republic of China formally presented a replica of this map as a gift to the South African government in conjunction with the exhibition. In official statements and popular media coverage alike, the map was described as evidence of a distinctly Chinese approach to global relations, based on benevolence and mutual respect. In particular, the map was ahistorically intertwined with the legacy of Zheng He’s diplomatic expeditions, which reached the East African coast in the early 1400s. To the cartographic historian, however, the depiction of Africa in the Da Ming Hunyi Tu is clearly derived from non-Chinese sources that predate Zheng He’s expeditions. This article examines the ways in which the map has been divorced from its original context to suit modern needs, exemplifying the deployment of cartography to deflect anxieties about the nature of Chinese economic influence in South Africa.

Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.

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Cuscó, Ivon; Medrano, Andrés; Gener, Blanca; Vilardell, Mireia; Gallastegui, Fátima; Villa, Olaya; González, Eva; Rodríguez-Santiago, Benjamín; Vilella, Elisabet; Del Campo, Miguel; Pérez-Jurado, Luis A

2009-05-15

Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

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Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

A STUDY ON PRINTMAKING IN MING AND QING DYNSTIES IN CHINA

Institute of Scientific and Technical Information of China (English)

赵丽媛

2017-01-01

Ming and Qing Dynasties printmaking have a unique form of expression, color and content. This article focuses on the artistic characteristics of the woodcut New Year paintings in the Ming and Qing Dynasties. Ming and Qing printmaking simple, natural, bold. Ming and Qing Dynasties folk woodcut New Year paintings of the composition of the pursuit of integrity, rich, sym-metrical, so that the composition of the screen harmony and unity. It is worth learning for our absorption.

The Tūqmāq and the Ming China: The Tūqmāq and the Chinese Relations during the Ming Period (1394–1456

Directory of Open Access Journals (Sweden)

Kenzheakhmet N.

2017-12-01

Full Text Available Objective: Little is known about diplomatic relations between the Jūchīd Ulūs and Ming China (1368–1644, even though some evidence of early tributary trade relations exists. The first extant Chinese account about the country of Salai (Saray dates to around 1394, when accounts of diplomatic exchange between the Ming court and the Jūchīd Ulūs began to appear in the Ming shilu (The Veritable Records of the Ming. Research materials: This article analyzes the Ming shilu in order to understand the character of Chinese knowledge about the Jūchīd Ulūs during their years of contact between 1394 and 1456. Additional sources like geographic accounts and maps help define the extent of Chinese knowledge about the khanate, clarify the kinds of information that the Chinese sought and the reasons why, and measure the influence of cross-cultural contact on Ming Chinese understanding of the Jūchīd Ulūs. Results and novelty of the research: The Ming shilu suggests that at least by the end of the fourteenth and the early years of the fifteenth century, Salai (Saray became an integral, and possibly the most important, element in the name that the Ming court used for the country of the Jūchīd Ulūs. The Persian and Mongol historians used the term Tūqmāq and Togmog to refer to the Jūchīd Ulūs, while Ming Chinese historians used the term Tuohema to refer to the Jūchīd Ulūs or the whole Dasht-i Qipchāq, in post-Mongol Central Eurasia. The diplomatic contact between Ming China and the Tuohuma occurred through the Chinese system of tribute trade during the mid-fifteenth century. Under the reign of Yongle (1402–1424, Zhengtong (1435–1449, and Jingtai (1449–1457, the foundations for a flourishing relationship between Ming China and the Jūchīd Ulūs were established. At that time, the Chinese knew the Jūchīd Ulūs by the name Salai (Saray and Tuohuma (Tūqmāq. Despite the political turmoil that erupted after the fall of the Jūchīd Ul

Multiple cell adhesion molecules shaping a complex nicotinic synapse on neurons.

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Triana-Baltzer, Gallen B; Liu, Zhaoping; Gounko, Natalia V; Berg, Darwin K

2008-09-01

Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses.

Evaluation of replacing wheat flour with chia flour (Salvia hispanica L. in pasta

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Matheus Rodrigues Oliveira

2015-08-01

Full Text Available In recent years, chia (Salvia hispanica L. has become increasingly more prevalent in the Brazilian diet and has triggered the interests of many researchers due to its functional properties and associated health benefits. The objective of this study was to develop pasta with different percentages of chia flour in lieu of wheat flour, and to evaluate the impact of chia on the nutritional, technological, and sensory properties of pasta. Pastas were prepared by replacing 7.5% (T1, 15% (T2, and 30% (T3 of wheat flour with chia flour relative to the control formulation (C. The quality of the pastas were evaluated through cooking tests (increase in weight and volume, cooking time, and loss of solids in the cooking water, chemical composition (moisture, fat, fiber, protein, ash, and carbohydrates, and color, using a Minolta colorimeter and sensory analysis by means of acceptance testing. Pasta made with chia flour had higher nutritional value and superior technological characteristics than did the control. Sensory analysis results showed that pasta with 7.5% chia flour had higher rates of acceptability in terms of the flavor, while the control pasta prevailed in terms of color and texture.

Localization of mineralocorticoid receptors at mammalian synapses.

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Eric M Prager

Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

Eyebrow Shapes of Chinese Empresses of the Ming and Qing Dynasties.

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Hwang, Kun; Yoo, Seong Kyung

2018-03-14

The aim of this study was to analyze eyebrow shapes in portraits of Chinese empresses of Ming and Qing dynasties.The frontal portraits of 20 Ming empresses and 24 of Qing in which the eye and eyebrows were identifiable were measured and analyzed. The arch shape did not differ significantly (P > 0.05) between Ming and Qing. The head-up type (66.6%) was significantly more common (P Qing empresses were classified as 5 arch types: L (Lamas), A (Anastasia), H (Hwang), M (Empress Ma), and D (Empress Du). In Ming, type-H (45.0%) was the most frequent, followed by type-D (25.0%). In Qing, type-L (45.8%) was the most frequent, followed by type-H (16.7%) and type-D (16.7%). The relative eyebrow width (REW) of Ming and Qing was 1.59 ± 0.28. The REW of Qing (1.63 ± 0.30) and Ming (1.55 ± 0.26) did not differ significantly. The relative medial height (RMH, 1.05 ± 0.20) and relative lateral height (RLH; 1.05 ± 0.21) were the same, and greater than the relative mid-pupillary height (RPH; 0.84 ± 0.19; P Qing (1.02 ± 0.16) did not differ significantly. The RLH likewise did not differ significantly between Ming (1.01 ± 0.21) and Qing (1.08 ± 0.22). However, the RPH of Ming (0.91 ± 0.21) was significantly (P = 0.042) greater than Qing (0.79 ± 0.17). The relative brow thickness (RBT) of Qing (0.13 ± 0.06) was significantly (p = 0.033) greater than Ming (0.17 ± 0.06). The RBT of Ming and Qing was 0.15 ± 0.06 and increased with time (P = 0.023).The results of this study may be useful for brow lift or the tattooing.

Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

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Zilong Gao

2016-12-01

Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

Don't Just Pet Your Chia.

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Hershey, David R.

1995-01-01

Presents ways to use ChiaPets to link biology-related topics such as taxonomy, morphology, ethnobotany, economic botany, hydroponics, salinity, photomorphogenesis, and phototropism with food and fertilizer chemistry, mathematics, art, and history. (MKR)

Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons

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Sampathkumar, Charanya; Wu, Yuan-Ju; Vadhvani, Mayur; Trimbuch, Thorsten; Eickholt, Britta; Rosenmund, Christian

2016-01-01

Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. DOI: http://dx.doi.org/10.7554/eLife.19374.001 PMID:27782879

A small RNA controls expression of the chitinase ChiA in Listeria monocytogenes

DEFF Research Database (Denmark)

Nielsen, Jesper S; Larsen, Marianne Halberg; Lillebæk, Eva Maria Sternkopf

2011-01-01

role of LhrA in L. monocytogenes. To this end, we determined the effects of LhrA on global-wide gene expression. We observed that nearly 300 genes in L. monocytogenes are either positively or negatively affected by LhrA. Among these genes, we identified lmo0302 and chiA as direct targets of LhrA, thus...... establishing LhrA as a multiple target regulator. Lmo0302 encodes a hypothetical protein with no known function, whereas chiA encodes one of two chitinases present in L. monocytogenes. We show here that LhrA acts as a post-transcriptional regulator of lmo0302 and chiA by interfering with ribosome recruitment......, and we provide evidence that both LhrA and Hfq act to down-regulate the expression of lmo0302 and chiA. Furthermore, in vitro binding experiments show that Hfq stimulates the base pairing of LhrA to chiA mRNA. Finally, we demonstrate that LhrA has a negative effect on the chitinolytic activity of L...

Fatty acids profile of chia oil-loaded lipid microparticles

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M. F. Souza

Full Text Available ABSTRACT Encapsulation of poly-unsaturated fatty acid (PUFAis an alternative to increase its stability during processing and storage. Chia (Salvia hispanica L. oil is a reliable source of both omega-3 and omega-6 and its encapsulation must be better evaluated as an effort to increase the number of foodstuffs containing PUFAs to consumers. In this work chia oil was extracted and encapsulated in stearic acid microparticles by the hot homogenization technique. UV-Vis spectroscopy coupled with Multivariate Curve Resolution with Alternating Least-Squares methodology demonstrated that no oil degradation or tocopherol loss occurred during heating. After lyophilization, the fatty acids profile of the oil-loaded microparticles was determined by gas chromatography and compared to in natura oil. Both omega-3 and omega-6 were effectively encapsulated, keeping the same omega-3:omega-6 ratio presented in the in natura oil. Calorimetric analysis confirmed that encapsulation improved the thermal stability of the chia oil.

Application of enzymatic methods for chia (Salvia hispanica L oil extraction

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Norma Ciau-Solís

2016-07-01

Full Text Available Aim. The aim was to evaluate the use of different enzymatic treatments on the oil extraction yield from Chia (Salvia hispanica L. seeds Methods. Enzymatic extraction was performed by treating of whole and degummed chia flours with different conditions of enzyme concentration, pH and temperature. Commercial enzymes were employed: Viscozyme LTM (endo-1,3 (4-betaglucanase derived from Aspergillus aculeatus, with 100 FBG g (Beta Glucanase-unit Fungal and Neutrase0.8LTM, neutral protease with 0.8 AU-NH/g of activity, derived from Bacillus amyloliquefaciens. Results. All treatments of enzymatic oil extraction were different (P <0.05 and the maximum oil yield obtained was 9.35%. Conclusion. Oil extraction using enzymatic methods is not a viable for chia seed

Effect of baking and storage on the fatty acid composition of cookies with chia seed meal

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Chia (Salvia hispanica L.) seed is an ancient crop of the Aztecs that has recently gained interest as a functional food. Chia seeds are a good source of polyphenolic compounds with antioxidant activity. However, the effect of baking and storage on the antioxidant properties of chia seed meal is not ...

Microstructure, chemical composition and mucilage exudation of chia (Salvia hispanica L.) nutlets from Argentina.

Science.gov (United States)

Capitani, Marianela I; Ixtaina, Vanesa Y; Nolasco, Susana M; Tomás, Mabel C

2013-12-01

The micromorphology and anatomy of nutlets, myxocarpy (mucilage exudation) and mucilage structure of Argentinean chia were described using scanning electron microscopy (SEM). The proximal composition of nutlets and mucilage was also studied. Chia nutlets are made up of a true seed and a pericarp enclosing the seed; they are small, glabrous, elliptic and apically rounded. The pericarp has cuticle, exocarp, mesocarp and bone cells vertically arranged and endocarp. The myxocarpy was carefully recorded by SEM. After 5 min in contact with water, the cuticle of nutlets is broken and the exocarp cell content gradually surrounds the rest of the nutlet. The proximal composition of chia nutlets was studied; fat is the major component (327 ± 8.0 g kg(-1)) followed by protein (293 ± 4.0 g kg(-1)) and fiber (276 ± 1.0 g kg(-1)). Extractions of chia nutlets with water at room temperature yielded 38 ± 1.0 g kg(-1) (dry basis) of mucilage. The fresh mucilage structure was similar to a network of open pores. The freeze-dried crude mucilage contained more ash, residual fat and protein than commercial guar and locust bean gum. The solubility of 10.0 g L(-1) w/v solution of chia freeze-dried crude mucilage in water increased with temperature, being maximal at 60 °C (870 g kg(-1)). The results obtained show a fast exudation of chia mucilage when nutlets are in contact with water. The freeze-dried crude mucilage hydrates easily in water, even at low temperatures. Chia nutlets have mucilaginous substances, with interesting functional properties from a technological and physiological point of view. © 2013 Society of Chemical Industry.

Espina: A Tool for the Automated Segmentation and Counting of Synapses in Large Stacks of Electron Microscopy Images

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Morales, Juan; Alonso-Nanclares, Lidia; Rodríguez, José-Rodrigo; DeFelipe, Javier; Rodríguez, Ángel; Merchán-Pérez, Ángel

2011-01-01

The synapses in the cerebral cortex can be classified into two main types, Gray's type I and type II, which correspond to asymmetric (mostly glutamatergic excitatory) and symmetric (inhibitory GABAergic) synapses, respectively. Hence, the quantification and identification of their different types and the proportions in which they are found, is extraordinarily important in terms of brain function. The ideal approach to calculate the number of synapses per unit volume is to analyze 3D samples reconstructed from serial sections. However, obtaining serial sections by transmission electron microscopy is an extremely time consuming and technically demanding task. Using focused ion beam/scanning electron microscope microscopy, we recently showed that virtually all synapses can be accurately identified as asymmetric or symmetric synapses when they are visualized, reconstructed, and quantified from large 3D tissue samples obtained in an automated manner. Nevertheless, the analysis, segmentation, and quantification of synapses is still a labor intensive procedure. Thus, novel solutions are currently necessary to deal with the large volume of data that is being generated by automated 3D electron microscopy. Accordingly, we have developed ESPINA, a software tool that performs the automated segmentation and counting of synapses in a reconstructed 3D volume of the cerebral cortex, and that greatly facilitates and accelerates these processes. PMID:21633491

ESPINA: a tool for the automated segmentation and counting of synapses in large stacks of electron microscopy images

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Juan eMorales

2011-03-01

Full Text Available The synapses in the cerebral cortex can be classified into two main types, Gray’s type I and type II, which correspond to asymmetric (mostly glutamatergic excitatory and symmetric (inhibitory GABAergic synapses, respectively. Hence, the quantification and identification of their different types and the proportions in which they are found, is extraordinarily important in terms of brain function. The ideal approach to calculate the number of synapses per unit volume is to analyze three-dimensional samples reconstructed from serial sections. However, obtaining serial sections by transmission electron microscopy is an extremely time consuming and technically demanding task. Using FIB/SEM microscopy, we recently showed that virtually all synapses can be accurately identified as asymmetric or symmetric synapses when they are visualized, reconstructed and quantified from large three-dimensional tissue samples obtained in an automated manner. Nevertheless, the analysis, segmentation and quantification of synapses is still a labor intensive procedure. Thus, novel solutions are currently necessary to deal with the large volume of data that is being generated by automated 3D electron microscopy. Accordingly, we have developed ESPINA, a software tool that performs the automated segmentation and counting of synapses in a reconstructed 3D volume of the cerebral cortex, and that greatly facilitates and accelerates these processes.

Regulation of dopamine D1 receptor dynamics within the postsynaptic density of hippocampal glutamate synapses.

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Laurent Ladepeche

Full Text Available Dopamine receptor potently modulates glutamate signalling, synaptic plasticity and neuronal network adaptations in various pathophysiological processes. Although key intracellular signalling cascades have been identified, the cellular mechanism by which dopamine and glutamate receptor-mediated signalling interplay at glutamate synapse remain poorly understood. Among the cellular mechanisms proposed to aggregate D1R in glutamate synapses, the direct interaction between D1R and the scaffold protein PSD95 or the direct interaction with the glutamate NMDA receptor (NMDAR have been proposed. To tackle this question we here used high-resolution single nanoparticle imaging since it provides a powerful way to investigate at the sub-micron resolution the dynamic interaction between these partners in live synapses. We demonstrate in hippocampal neuronal networks that dopamine D1 receptors (D1R laterally diffuse within glutamate synapses, in which their diffusion is reduced. Disrupting the interaction between D1R and PSD95, through genetical manipulation and competing peptide, did not affect D1R dynamics in glutamatergic synapses. However, preventing the physical interaction between D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of diffusing D1R. Together, these data provide direct evidence that the interaction between D1R and NMDAR in synapses participate in the building of the dopamine-receptor-mediated signalling, and most likely to the glutamate-dopamine cross-talk.

Addition of chia seed mucilage for reduction of fat content in bread and cakes.

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Fernandes, Sibele Santos; Salas-Mellado, Myriam de Las Mercedes

2017-07-15

In this study, breads and chocolate cakes were prepared with different levels of chia mucilage dried at 50°C or lyophilized as fat, resulting in healthier products. Results indicated that breads and chocolate cakes made with chia mucilage can replace up to 50% of fat without affecting the technological and physical characteristics. The replacement of 75% of fat, for both types of mucilage, had a significant reduction in fat content of 56.6% in breads and 51.6% in cakes, producing a slight decrease in the technological characteristics of the products. Sensorial parameters showed good acceptability, with greater purchase intent for both products when added with chia mucilage dried at 50°C. Therefore, chia mucilage proved to be a new alternative for replacing fat in food products, preserving the quality attributes and making them healthier foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection and Identification of the First Viruses in Chia (Salvia hispanica

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Marcos G. Celli

2014-09-01

Full Text Available Chia (Salvia hispanica, an herbaceous plant native to Latin America, has become important in the last 20 years due to its beneficial effects on health. Here, we present the first record and identification of two viruses in chia plants. The comparison of the complete nucleotide sequences showed the presence of two viral species with the typical genome organization of bipartite New World begomovirus, identified as Sida mosaic Bolivia virus 2 and Tomato yellow spot virus, according to the ICTV taxonomic criteria for begomovirus classification. DNA-A from Sida mosaic Bolivia virus 2 exhibited 96.1% nucleotide identity with a Bolivian isolate of Sida micrantha, and Tomato yellow spot virus showed 95.3% nucleotide identity with an Argentine bean isolate. This is the first report of begomoviruses infecting chia as well as of the occurrence of Sida mosaic Bolivia virus 2 in Argentina.

Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

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Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

2017-03-15

Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses

Omega-3 fatty acids and oxidative stability of ice cream supplemented with olein fraction of chia (Salvia hispanica L.) oil

OpenAIRE

Ullah, Rahman; Nadeem, Muhammad; Imran, Muhammad

2017-01-01

Background Chia (Salvia hispanica L.) has been regarded as good source of polyunsaturated omega-3 fatty acids with cardiac, hepatic, hypotensive, antiallergic and antidiabetic role. Concentration of omega-3 fatty acids in chia oil can be enhanced by fractionation. Olein/low melting fraction of chia oil has higher concentration of omega-3 fatty acids. Therefore, main objective of current investigation was determination of various concentration effect of olein fraction of chia oil on omega-3 fa...

The effect of gamma radiation on Chia (Salvia hispanica L.) edible film

International Nuclear Information System (INIS)

Chierentin, Gabriel S.; Teixeira, Bruna S.; Del Mastro, Nélida L.

2017-01-01

Edible films and coatings have received considerable attention in recent years for their advantages over synthetic films for edible packaging materials. Chia seeds (Salvia hispanica L.) have functional and important nutritional values: protein content (15 - 25%), fats (30 - 33%), carbohydrates (26 - 41%), dietary fiber (18 - 30%), and ash (4-5%). It also contains a high amount of vitamins, minerals, and antioxidants. Mucilage of chia, a natural exudates from chia seeds, is mainly composed of xylose, glucose and glucuronic acid forming a branched polysaccharide. In the present preliminary work whole chia seeds were irradiated in a "6"0Co source Gammacell 220 (AECL) with doses of 0, 5 and 10 kGy, dose rate about 0.8 kGy h"-"1. The irradiated seeds were crushed and soaked in an aqueous solution (6% w/w) together with glycerol (1% w/w), under magnetic stirring for 15 minutes at room temperature and poured into casting plates. The plates were placed in an oven with forced air circulation at 35 °C for at least 20 h. Water uptake, moisture, solubility and water activity of the films were established. The most expressive result was a decrease in water uptake with the increase of the radiation dose. Solubility remained almost unaffected by radiation in doses of 5kGy and moisture analysis showed also a decrease with dose. (author)

The effect of gamma radiation on Chia (Salvia hispanica L.) edible film

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Chierentin, Gabriel S.; Teixeira, Bruna S.; Del Mastro, Nélida L., E-mail: gabrielsouza.ch@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2017-11-01

Edible films and coatings have received considerable attention in recent years for their advantages over synthetic films for edible packaging materials. Chia seeds (Salvia hispanica L.) have functional and important nutritional values: protein content (15 - 25%), fats (30 - 33%), carbohydrates (26 - 41%), dietary fiber (18 - 30%), and ash (4-5%). It also contains a high amount of vitamins, minerals, and antioxidants. Mucilage of chia, a natural exudates from chia seeds, is mainly composed of xylose, glucose and glucuronic acid forming a branched polysaccharide. In the present preliminary work whole chia seeds were irradiated in a {sup 60}Co source Gammacell 220 (AECL) with doses of 0, 5 and 10 kGy, dose rate about 0.8 kGy h{sup -1}. The irradiated seeds were crushed and soaked in an aqueous solution (6% w/w) together with glycerol (1% w/w), under magnetic stirring for 15 minutes at room temperature and poured into casting plates. The plates were placed in an oven with forced air circulation at 35 °C for at least 20 h. Water uptake, moisture, solubility and water activity of the films were established. The most expressive result was a decrease in water uptake with the increase of the radiation dose. Solubility remained almost unaffected by radiation in doses of 5kGy and moisture analysis showed also a decrease with dose. (author)

Effects on bread and oil quality after functionalization with microencapsulated chia oil.

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González, Agustín; Martínez, Marcela L; León, Alberto E; Ribotta, Pablo D

2018-03-23

Omega-3 and omega-6 fatty acids-rich oils suffer oxidation reactions that alter their chemical and organoleptic quality. Microencapsulation can be a powerful tool for protection against ambient conditions. In the present study, the addition of microencapsulated chia oil as an ingredient in bread preparations and its effect on the technological and chemical quality of breads was investigated. Microencapsulation of chia oil was carried out by freeze-drying with soy proteins as wall material and oil release was determined under in vitro gastric and intestinal conditions. Encapsulated oil-containing bread showed no differences in specific volume, average cell area, firmness and chewiness with respect to control bread. Unencapsulated oil-containing bread showed a marked increase in hydroperoxide values respect to control, whereas encapsulated oil-containing bread values were not affected by baking and bread storage. The fatty acid profiles showed a decrease of 13% and 16%, respectively, in α-linolenic acid in the encapsulated and unencapsulated oils with respect to bulk chia oil. Sensory analysis showed no significant differences between bread samples. The addition of encapsulated chia oil did not alter the technological quality of breads and prevented the formation of hydroperoxide radicals. A ration of encapsulated oil-containing bread contributes 60% of the recommended dietary intake of omega-3 fatty acids. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Effect of chia seed (Salvia hispanica L.) consumption on cardiovascular risk factors in humans: a systematic review

OpenAIRE

Ferreira, Cynthia de Souza; Fomes, Lucilia de Fátima de Sousa; Silva, Gilze Espirito Santo da; Rosa, Glorimar

2015-01-01

Introduction: chia is a seed rich in such nutrients as proteins, n-3 fatty acids and especially alpha-linolenic acid (ALA), minerals, fibers and antioxidants. Efforts have been made to assess whether human consumption of chia can reduce cardiovascular risk factors; however, it has not been established as effective and the findings of the few studies to have looked into the matter are inconsistent. Aim: to systematize the findings of studies assessing the effect the consumption of chia seed, e...

The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain.

Science.gov (United States)

Peng, Y; Lu, Z; Li, G; Piechowicz, M; Anderson, M; Uddin, Y; Wu, J; Qiu, S

2016-07-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which has a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD.

LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

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Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

2016-07-01

Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

Mr.Seah Moon Ming Leadership & Management

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

@@ Life and Work Philosophy Seah Moon Ming considers life a continuous journey of learning,adaptation and attainment of goals.He believes that as long as there are changes,you will need to learn - to learn to adapt and to play a useful role in a dynamic and ever-changing world.

Activity-dependent control of NMDA receptor subunit composition at hippocampal mossy fibre synapses.

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Carta, Mario; Srikumar, Bettadapura N; Gorlewicz, Adam; Rebola, Nelson; Mulle, Christophe

2018-02-15

CA3 pyramidal cells display input-specific differences in the subunit composition of synaptic NMDA receptors (NMDARs). Although at low density, GluN2B contributes significantly to NMDAR-mediated EPSCs at mossy fibre synapses. Long-term potentiation (LTP) of NMDARs triggers a modification in the subunit composition of synaptic NMDARs by insertion of GluN2B. GluN2B subunits are essential for the expression of LTP of NMDARs at mossy fibre synapses. Single neurons express NMDA receptors (NMDARs) with distinct subunit composition and biophysical properties that can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells from mice of both sexes, we found that mossy fibre (MF) synapses display a markedly lower proportion of GluN2B-containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known. Here we show that long-term potentiation (LTP) of NMDARs, which is selectively expressed at MF-CA3 pyramidal cell synapses, triggers a modification in the subunit composition of synaptic NMDARs by insertion of GluN2B. This activity-dependent recruitment of GluN2B at mature MF-CA3 pyramidal cell synapses contrasts with the removal of GluN2B subunits at other glutamatergic synapses during development and in response to activity. Furthermore, although expressed at low levels, GluN2B is necessary for the expression of LTP of NMDARs at MF-CA3 pyramidal cell synapses. Altogether, we reveal a previously unknown activity-dependent regulation and function of GluN2B subunits that may contribute to the heterogeneous plasticity induction rules in CA3 pyramidal cells. © 2017 Centre Nationnal de la Recherche Scientifique. The Journal of Physiology © 2017 The Physiological Society.

Use of a chiA probe for detection of chitinase genes in bacteria from the Chesapeake Bay

Digital Repository Service at National Institute of Oceanography (India)

Ramaiah, N.; Hill, R.T.; Chun, J.; Ravel, J.; Matte, M.H.; Straube, W.L.; Colwell, R.R.

PCR primers specific for the chiA gene were designed by alignment and selection of highly conserved regions of chiA sequences from Serratia marcescens, Alteromonas sp., Bacillus circulans and Aeromonas caviae. These primers were used to amplify a...

Metabolomics driven analysis by UAEGC-MS and antioxidant activity of chia (Salvia hispanica L.) commercial and mutant seeds.

Science.gov (United States)

de Falco, Bruna; Fiore, Alberto; Rossi, Roberta; Amato, Mariana; Lanzotti, Virginia

2018-07-15

Chia is a food plant producing seeds which have seen increasing interest owing to their health benefits. This work is the first report on the metabolite profile, total polyphenols and antioxidant activity of chia seeds, determined by ultrasound-assisted extraction, coupled with gas chromatography-mass spectrometry (UAE GC-MS). Different chia sources were compared: two commercial (black and white) and three early flowering (G3, G8 and G17) mutant genotypes. Organic extracts were mainly composed of mono- and polyunsaturated fatty acids with alpha-linolenic being the most abundant. Polar extracts contained sucrose, methylgalactoside and glucose as main sugars. Antioxidant activity and total polyphenolic content were correlated. Chemical composition and yield potential of early flowering genotypes were different from commercial chia, and while white chia showed the highest content of omega-3 fatty acids, the high content of nutraceuticals in G17 and G8 suggests them as a potential source of raw materials for the food/feed industry. Copyright © 2018 Elsevier Ltd. All rights reserved.

Whole and crushed nutlets of chia (Salvia hispanica from Mexico as a source of functional gums

Directory of Open Access Journals (Sweden)

Maira Segura-Campos

2014-12-01

Full Text Available The objective of this study was to characterize the chemical and functional properties of Mexican chia (Salvia hispanica gums extracted from defatted whole and crushed nutlets using the Soxhlet and SFE-CO2 methods. Chia gums have interesting chemical and functional properties for the food industry. The oil and gum yields were in the range of 1.98-16.42% and 5.81-12.60%, respectively. The defatting procedure did not affect significantly the oil and gum extraction; the nutlet type (whole or crushed was the only parameter influencing the yield. The proximate composition and the protein and fiber contents of chia gum were evaluated. Low contents of protein and fiber and high NFE levels were found in whole nutlet gums. The functional properties of chia gum extracted from whole and crushed nutlets with the Soxhlet and SFE-COs methods showed the following ranges of water absorption capacity of 62.64 to 143.66 g/g, water adsorption capacity of 0.69 to 1.35 g/g, and water and oil holding capacity of 100 to 149.28 g/g and19.5 to 40.4 g/g, respectively. The rheological behavior exhibited by the gums was pseudoplastic or shear thinning. From a functional perspective, chia gum is an important food component due its emulsifier and stabilizer potentials.

Analytical Characterization of Butter Oil Enriched with Omega-3 and 6 Fatty Acid Sthrough Chia (Salvia hispanica L.) Seed Oil

OpenAIRE

Muhammad Nadeem; Muhammad Ajmal; Fazal Rahman; Muhammad Ayaz

2015-01-01

Analytical characterization of blends of butter oil and chia (Salvia hispanica L.) seed oil was performed. Chia oil was added in butter oil at four different levels i.e. 6.25%, 12.5%, 18.75% and 25% (T1, T2, T3 and T4), butter oil without any addition of chia oil served as control. Blends of butter oil and chia oil were packaged in tin containers, stored at ambient temperature (34±2oC) for 90-days. Iodine values of control, T1, T2, T3 and T4 were 36.85, 45.63, 57.22, 67.45 and 76.37 (cg/g).Co...

Effect of Qi Ming Granule on the choroidal circulation in diabetic patients

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Ke-Jun Li

2016-03-01

Full Text Available AIM:To investigate the effect of a Chinese medicine(Qi Ming granuleon the retinal and choroidal circulation in diabetes patients. METHODS: According to the results of fundus fluorescein angiography(FFA, all the 45 diabetes patients were divided into no diabetic retinopathy(NDRgroup and nonproliferative diabetic retinopathy(NPDRgroup. All subjects were examined by FFA and indocyanine green angiography(ICGAat the same time. After taken Qi Ming granule for 3mo, all subjects were examined by the same method. FFA and ICGA were used to evaluate the retinal and choroidal circulation and their features. The key points were filling time for the retinal and choroidal circulation before and after treatments. The accuracy data was used to evaluate the effect.RESULTS: After taken Qi Ming granule for 3mo, there were significant decrease of the retina and the choroid filling time in NDR and NPDR groups. The occurrence rate of various abnormal angiographic features were significantly decreased. CONCLUSION: Qi Ming granule can accelerate the blood flow of retina and choroid, improve the blood circulation in diabetes patients, and delay the occurrence and development of diabetic retinopathy.

Glutamatergic System and Schizophrenia

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Osman Ozdemir

2016-12-01

Full Text Available Glutamate is the major excitatory neurotransmitter in the brain. It has a role several cognitive functions including learning, memory and perception. Glutamatergic neurotransmission is also involved in regulating neuronal migration, synaptogenesis, and the pruning neurons. Glutamatergic exci-totoxicity has been implicated in various neuropsychiatric disorders. Accumulating evidence suggests that glutamatergic dysfunction may contribute to the pathogenesis of schizophrenia. The N-methyl-D-aspartic acid (NMDA receptor antagonists such as phencyclidine and ketamine can cause both the positive and negative symptoms psychotic symptoms in normal humans, and worsen these symptoms in persons with schizophrenia. Hence, it has been hypotesized that schizophrenia may be associated with decreased NMDA-receptor activity. According to the hypothesis, NMDA reseptor hypofunction can lead to decreased inhibition of glutamatergic neurons and excessive glutamate release. Finally, the reduction of gray matter in several brain regions seen in patients with schizophrenia has been suggested to be the result of neurotoxicity mediated by NMDA receptors. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 394-405

Improvement of Chia Seeds with Antioxidant Activity, GABA, Essential Amino Acids, and Dietary Fiber by Controlled Germination Bioprocess.

Science.gov (United States)

Gómez-Favela, Mario Armando; Gutiérrez-Dorado, Roberto; Cuevas-Rodríguez, Edith Oliva; Canizalez-Román, Vicente Adrián; Del Rosario León-Sicairos, Claudia; Milán-Carrillo, Jorge; Reyes-Moreno, Cuauhtémoc

2017-12-01

Chia (Salvia hispanica L.) plant is native from southern Mexico and northern Guatemala. Their seeds are a rich source of bioactive compounds which protect consumers against chronic diseases. Germination improves functionality of the seeds due to the increase in the bioactive compounds and associated antioxidant activity. The purpose of this study was to obtain functional flour from germinated chia seeds under optimized conditions with increased antioxidant activity, phenolic compounds, GABA, essential amino acids, and dietary fiber with respect to un-germinated chia seeds. The effect of germination temperature and time (GT = 20-35 °C, Gt = 10-300 h) on protein, lipid, and total phenolic contents (PC, LC, TPC, respectively), and antioxidant activity (AoxA) was analyzed by response surface methodology as optimization tool. Chia seeds were germinated inside plastic trays with absorbent paper moisturized with 50 mL of 100 ppm sodium hypochlorite dissolution. The sprouts were dried (50 °C/8 h) and ground to obtain germinated chia flours (GCF). The prediction models developed for PC, LC, TPC, and AoxA showed high coefficients of determination, demonstrating their adequacy to explain the variations in experimental data. The highest values of PC, LC, TPC, and AoxA were obtained at two different optimal conditions (GT = 21 °C/Gt = 157 h; GT = 33 °C/Gt = 126 h). Optimized germinated chia flours (OGCF) had higher PC, TPC, AoxA, GABA, essential amino acids, calculated protein efficiency ratio (C-PER), and total dietary fiber (TDF) than un-germinated chia seed flour. The OGCF could be utilized as a natural source of proteins, dietary fiber, GABA, and antioxidants in the development of new functional beverages and foods.

[Chemical composition and chromaticity characteristic of Jilan glaze of Ming and Qing official kilns].

Science.gov (United States)

Wu, Jun-ming; Zhang, Mao-lin; Li, Qi-jiang; Wu, Juan; Quan, Kui-shan; Cao, Jian-wen

2012-08-01

Color glazes of Ming and Qing official kilns are excellent representatives of the famous ancient Chinese porcelains. The study of official ware with Jilan glaze has been an important topic. But it made slow progress due to the rarity of samples with strict production management and using system. The recipes, chemical composition and chromaticity characteristic of the Jilan samples excavated from official kilns in the Ming and Qing dynasties were first discussed by systematical testing with the energy dispersive X-ray fluorescence (EDXRF) and color difference meter. The results showed that the porcelain stone content in Jilan bodies of official kiln in the Ming dynasty is higher than the samples of the Qing dynasty. The manganese content in Jilan glazes of the Ming dynasty is higher than that in the Qing dynasty, while the glaze ash addition and the lightness value in the glaze are opposite.

Physical-chemical characterization of quinoa (Chenopodium quinoa Willd., amaranth (Amaranthus caudatus L., and chia (Salvia hispanica L. flours and seeds

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Olga Lucía Torres Vargas

2018-04-01

Full Text Available Quinoa, amaranth, and chia flours have considerable amounts of protein, starch, dietary fiber, lipids, minerals, vitamins, and bioactive components, which provide in them exceptional properties for human nutrition. The aim of this research was the physical-chemical characterization of quinoa, amaranth, and chia flours and seeds through proximal, optical, functional, thermal, and structural analyses. From the results obtained during the proximal analysis, considerable proportions were determined of protein and fiber for the three flours, with the highest values in chia flour at 28.56% and 39.8%, respectively. These results were corroborated by optical microscopy analysis performed on longitudinal cuts in the three types of seeds. Thermal parameters indicated that the three flours presented irreversible thermal degradation processes and glass transition change for amaranth and chia flours at temperatures above 100ºC. Structural characterization of the flours via FTIR have allowed detecting differences in protein and lipid characteristic absorption bands. Diffraction patterns of type A starch were identified for quinoa and amaranth flours, while the chia flour had two crystalline peaks corresponding to calcium and magnesium. Scanning electron microscopy images showed starch aggregates in the quinoa flour, a complex structure composed of spherical proteins that surround the starches in amaranth flour and fibrous structures and spherical proteins in chia flour.

Climatic zoning of chia (Salvia hispanica L. in Chile using a species distribution model

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Daniela Cortés

2017-12-01

Full Text Available Salvia hispanica L., known as chia, is a plant species originally from tropical and subtropical Mesoamerica. It is economically important because its seeds produce omega-3, thus its demand has increased in Chile and internationally. As there is no commercial production in Chile, we investigated the places in the country where this species could be cultivated in order to satisfy at the least the national demand. The aim of the study was to quantify the main climatic requirements of chia and to produce a climatic aptitude map for chia cultivation in Chile. The methodology was based on the Maxent species distribution model. We used 78 georeferenced data points where chia is grown throughout the world, mostly from the GBIF database, along with raster climatic layers from the Worldclim project. We estimated the performance curves of annual precipitation and temperature along with their respective optimal and critical values, in analogy with the Ecocrop method. The maps used two scenarios for crops in different conditions, with and without irrigation. The results indicated that the intermediate depression and coastal edge of mainly the Arica y Parinacota, Tarapacá, Antofagasta and Atacama regions have optimum conditions for irrigated crops, but it would be impossible in rainfed conditions. We conclude that chia’s cultivation niche is reduced due to its tropical climate requirements; however, it can be cultivated under irrigation in northern Chile.

Climatic zoning of chia (Salvia hispanica L.) in Chile using a species distribution model

International Nuclear Information System (INIS)

Cortés, D.; Silva, H.; Baginsky, C.; Morales, L.

2017-01-01

Salvia hispanica L., known as chia, is a plant species originally from tropical and subtropical Mesoamerica. It is economically important because its seeds produce omega-3, thus its demand has increased in Chile and internationally. As there is no commercial production in Chile, we investigated the places in the country where this species could be cultivated in order to satisfy at the least the national demand. The aim of the study was to quantify the main climatic requirements of chia and to produce a climatic aptitude map for chia cultivation in Chile. The methodology was based on the Maxent species distribution model. We used 78 georeferenced data points where chia is grown throughout the world, mostly from the GBIF database, along with raster climatic layers from the Worldclim project. We estimated the performance curves of annual precipitation and temperature along with their respective optimal and critical values, in analogy with the Ecocrop method. The maps used two scenarios for crops in different conditions, with and without irrigation. The results indicated that the intermediate depression and coastal edge of mainly the Arica y Parinacota, Tarapacá, Antofagasta and Atacama regions have optimum conditions for irrigated crops, but it would be impossible in rainfed conditions. We conclude that chia’s cultivation niche is reduced due to its tropical climate requirements; however, it can be cultivated under irrigation in northern Chile.

Climatic zoning of chia (Salvia hispanica L.) in Chile using a species distribution model

Energy Technology Data Exchange (ETDEWEB)

Cortés, D.; Silva, H.; Baginsky, C.; Morales, L.

2017-07-01

Salvia hispanica L., known as chia, is a plant species originally from tropical and subtropical Mesoamerica. It is economically important because its seeds produce omega-3, thus its demand has increased in Chile and internationally. As there is no commercial production in Chile, we investigated the places in the country where this species could be cultivated in order to satisfy at the least the national demand. The aim of the study was to quantify the main climatic requirements of chia and to produce a climatic aptitude map for chia cultivation in Chile. The methodology was based on the Maxent species distribution model. We used 78 georeferenced data points where chia is grown throughout the world, mostly from the GBIF database, along with raster climatic layers from the Worldclim project. We estimated the performance curves of annual precipitation and temperature along with their respective optimal and critical values, in analogy with the Ecocrop method. The maps used two scenarios for crops in different conditions, with and without irrigation. The results indicated that the intermediate depression and coastal edge of mainly the Arica y Parinacota, Tarapacá, Antofagasta and Atacama regions have optimum conditions for irrigated crops, but it would be impossible in rainfed conditions. We conclude that chia’s cultivation niche is reduced due to its tropical climate requirements; however, it can be cultivated under irrigation in northern Chile.

Optimization of mucilage extraction from chia seeds (Salvia hispanica L.) using response surface methodology.

Science.gov (United States)

Orifici, Stefania C; Capitani, Marianela I; Tomás, Mabel C; Nolasco, Susana M

2018-02-25

Chia mucilage has potential application as a functional ingredient; advances on maximizing its extraction yield could represent a significant technological and economic impact for the food industry. Thus, first, the effect of mechanical agitation time (1-3 h) on the exudation of chia mucilage was analyzed. Then, response surface methodology was used to determine the optimal combination of the independent variables temperature (15-85 °C) and seed: water ratio (1: 12-1: 40.8 w/v) for the 2 h exudation that give maximum chia mucilage yield. Experiments were designed according to central composite rotatable design. A second-order polynomial model predicted the variation in extraction mucilage yield with the variables temperature and seed: water ratio. The optimal operating conditions were found to be temperature 85 °C and a seed: water ratio of 1: 31 (w/v), reaching an experimental extraction yield of 116 ± 0.21 g kg -1 (dry basis). The mucilage obtained exhibited good functional properties, mainly in terms of water-holding capacity, emulsifying activity, and emulsion stability. The results obtained show that temperature, seed: water ratio, and exudation time are important variables of the process that affect the extraction yield and the quality of the chia mucilage, determined according to its physicochemical and functional properties. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors.

Science.gov (United States)

Mota, Sandra I; Ferreira, Ildete L; Rego, A Cristina

2014-01-01

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (Aβ) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre- and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by Aβ in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analytical Characterization of Butter Oil Enriched with Omega-3 and 6 Fatty Acid Sthrough Chia (Salvia hispanica L. Seed Oil

Directory of Open Access Journals (Sweden)

Muhammad Nadeem

2015-12-01

Full Text Available Analytical characterization of blends of butter oil and chia (Salvia hispanica L. seed oil was performed. Chia oil was added in butter oil at four different levels i.e. 6.25%, 12.5%, 18.75% and 25% (T1, T2, T3 and T4, butter oil without any addition of chia oil served as control. Blends of butter oil and chia oil were packaged in tin containers, stored at ambient temperature (34±2oC for 90-days. Iodine values of control, T1, T2, T3 and T4 were 36.85, 45.63, 57.22, 67.45 and 76.37 (cg/g.Concentration of omega-3 fatty acids in T1, T2, T3 and T4 were 4.17%, 7.39%, 12.55% and 16.74%. The extent of omega-6 fatty acids in T1, T2, T3 and T4 was 2.81%, 2.94%, 3.15% and 3.32%.Concentration of omega-3 and 6 fatty acids in butter oil can be increased by chia oil.

78 FR 2478 - Culturally Significant Objects Imported for Exhibition Determinations: “Ming Masterpieces From...

Science.gov (United States)

2013-01-11

... ``Ming Masterpieces from the Shanghai Museum,'' imported from abroad for temporary exhibition within the... Determinations: ``Ming Masterpieces From the Shanghai Museum'' SUMMARY: Notice is hereby given of the following... at the Los Angeles County Museum of Art, Los Angeles, CA, from on or about March 3, 2013, until on or...

[Textual research on circulation of the Ming edition of Li Heng's Xiu zhen fang (Pocket Formulary)].

Science.gov (United States)

Yang, Jinping; Liu, Peng; Lu, Mingjing; Lu, Xing; Li, Shaolin; Jin, Xiumei

2015-03-01

Xiu zhen fang (Pocket Formulary) is a recipe book of the Ming Dynasty, inspired and managed by Zhu Su, compiled by Li Heng of liangyisuo (good physician house) in Zhou wangfu (Zhou's royal palace). The book was compiled and published twice during the reigns of the Hongwu and Yongle Emperors of the Ming Dynasty. Because of its high practicability, there were some editions in circulation, and the book was published several times only in the Ming Dynasty. At present, the earliest extanteditionwas the little character version of Yongle, and the version in the 4(th) year of Zhengde Emperor of the Ming Dynasty was a reprinting edition based on the Yongle edition, sharingthe same edition system. Most of the editions appeared after the reign of Zhengtong Emperor of the Ming Dynasty, titled by "kui ben (head version)" and "da quan (complete edition)" were the editionspublished in the local bookshops, which had rather distinct differences from the Yongle edition system not only in the its format but also in its contents.

Population growth, deforestation, and fuel substitution in Ming Beijing (Ecology, China)

Energy Technology Data Exchange (ETDEWEB)

Chiu, C.L. [Academy of Sinica, Taipei (Taiwan)

2003-03-01

This article investigates why people of Beijing started to burn coal instead of logs after the middle Ming Dynasty. The records of the city's population, illegal logging and the government's fuel policy showed the Beijing's population boom, which resulted in a stronger demand of cooking fuel and construction materials, had led to illegal logging. In the early 16th century, there were hardly any trees on the Yan Mountain north of Beijing. On the other hand, to provide huge amounts of fuel for the palace and offices, the government set up a charcoal works on the northern Tiahang Mountain, which is southwest of Beijing. In 1442, 57,000 tons firewood and charcoal were burned for official purposes. Even though the quantity declined later, it still consumed 30,000 tons firewood and charcoal a year during the middle of the 16th century. After the middle of the 15th century, forests around Beijing disappeared due to extensive logging. The prices of logs also went up. Therefore people started to use easily available coal. Since the late 15th century, written accounts of coal mining in the mountain west of Beijing were increasing. In the early Ming, Beijing's households burned logs. Since then, more and more adopted coal burning especially during the late Ming. The city became so dependent on West Mountain's coal mine that any northern invasion that crossed the Great Wall would cause a coal supply problem. Fuel substitution in Beijing throughout the Ming Dynasty was a good example of environmental change caused by urban development. After the loss of forests and the mass consumption of coal, the city's environment also changed. Ever since the late Ming, coal-burning-caused problems such as earth dumping and air pollution were worsening. Evidently, the city of Beijing was suffering from the decay of its environment since the late 16th century.

Fatty acids characterization, oxidative perspectives and consumer acceptability of oil extracted from pre-treated chia (Salvia hispanica L.) seeds.

Science.gov (United States)

Imran, Muhammad; Nadeem, Muhammad; Manzoor, Muhammad Faisal; Javed, Amna; Ali, Zafar; Akhtar, Muhammad Nadeem; Ali, Muhammad; Hussain, Yasir

2016-09-20

Chia (Salvia hispanica L.) seeds have been described as a good source of lipids, protein, dietary fiber, polyphenolic compounds and omega-3 polyunsaturated fatty acids. The consumption of chia seed oil helps to improve biological markers related to metabolic syndrome diseases. The oil yield and fatty acids composition of chia oil is affected by several factors such as pre-treatment method and size reduction practices. Therefore, the main mandate of present investigate was to study the effect of different seed pre-treatments on yield, fatty acids composition and sensory acceptability of chia oil at different storage intervals and conditions. Raw chia seeds were characterized for proximate composition. Raw chia seeds after milling were passed through sieves to obtain different particle size fractions (coarse, seed particle size ≥ 10 mm; medium, seed particle size ≥ 5 mm; fine, seed particle size ≤ 5 mm). Heat pre-treatment of chia seeds included the water boiling (100 C°, 5 min), microwave roasting (900 W, 2450 MHz, 2.5 min), oven drying (105 ± 5 °C, 1 h) and autoclaving (121 °C, 15 lbs, 15 min) process. Extracted oil from pre-treated chia seeds were stored in Tin cans at 25 ± 2 °C and 4 ± 1 °C for 60-days and examined for physical (color, melting point, refractive index), oxidative (iodine value, peroxide value, free fatty acids), fatty acids (palmitic, stearic, oleic, linoleic, α-linolenic) composition and sensory (appearance, flavor, overall acceptability) parameters, respectively. The proximal composition of chia seeds consisted of 6.16 ± 0.24 % moisture, 34.84 ± 0.62 % oil, 18.21 ± 0.45 % protein, 4.16 ± 0.37 % ash, 23.12 ± 0.29 % fiber, and 14.18 ± 0.23 % nitrogen contents. The oil yield as a result of seed pre-treatments was found in the range of 3.43 ± 0.22 % (water boiled samples) to 32.18 ± 0.34 % (autoclaved samples). The oil samples at day 0 indicated the

Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

Science.gov (United States)

Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

2016-01-01

A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

Towards a Collective Intelligence: Transmediality and the Wu Ming Project

Directory of Open Access Journals (Sweden)

Melina Anne Masterson

2014-11-01

Full Text Available Dagli albori della Seconda Repubblica in Italia,  le strategie di dominio sui mass media dell’ex premier Silvio Berlusconi hanno avuto un effetto considerevole sull’immaginario culturale italiano. In un approccio multisensoriale e multimediale alla scrittura, il collettivo Wu Ming mette in questione i paradigmi culturali che negli ultimi venti anni sono diventati egemonici. L’esperienza di un romanzo dei Wu Ming va ben oltre la parola stampata poiché cerca di stimolare tutti i cinque sensi per arricchire il modo in cui il lettore vive quello che c’è sulla pagina, dimostrando esempi chiari della «convergence culture» coniata da Henry Jenkins. Questo saggio esamina l’interazione tra parola e immagine messa in atto dal collettivo tramite il sito Pinterest e illustra come questo aspetto del loro progetto rappresenti un microcosmo di un approccio complessivo alla creazione estetica e alla pratica culturale. Inoltre, questo saggio descrive in che modo il processo collettivo di consumo portato avanti dai Wu Ming contribuisca alla formazione delle «communities of sentiment» di Arjun Appadurai e alla «intelligenza collettiva» di Jenkins. Queste sono formazioni che rivitalizzano il concetto di cultura popolare per la nostra epoca digitale e offrono un’alternativa ad un immaginario culturale italiano sovra-determinato dalle pratiche del Berlusconismo.

A Response to Stewart, McElwee, and Ming

Science.gov (United States)

Martin, Garry L.; Yu, C. T.

2010-01-01

In a recent article published in "The Behavior Analyst," Stewart, McElwee, and Ming (2010) suggested that "scientific experts in scientific contexts" should use more "technically accurate and precise labeling" when describing the Assessment of Basic Learning Abilities (ABLA) in published articles. They concluded by stating, "We believe that…

Analytical Characterization of Butter Oil Enriched with Omega-3 and 6 Fatty Acids Through Chia (Salvia hispanica L.) Seed Oil

International Nuclear Information System (INIS)

Nadeem, M.; Ajmal, M.; Rehman, F.; Ayaz, M.

2015-01-01

Analytical characterization of blends of butter oil and chia (Salvia hispanica L.) seed oil was performed. Chia oil was added in butter oil at four different levels i.e. 6.25 percentage, 12.5 percentage, 18.75 percentage and 25 percentage (T/sub 1/, T/sub 2/, T/sub 3/ and T/sub 4/), butter oil without any addition of chia oil served as control. Blends of butter oil and chia oil were packaged in tin containers, stored at ambient temperature (34±2 degree C) for 90-days. Iodine values of control, T/sub 1/, T/sub 2/, T/sub 3/ and T/sub 4/ were 36.85, 45.63, 57.22, 67.45 and 76.37 (cg/g percentage). Concentration of omega-3 fatty acids in T/sub 1/, T/sub 2/, T/sub 3/ and T/sub 4/ were 4.17 percentage, 7.39 percentage, 12.55 percentage and 16.74 percentage. The extent of omega-6 fatty acids in T/sub 1/, T/sub 2/, T/sub 3/ and T/sub 4/ was 2.81 percentage, 2.94 percentage, 3.15 percentage and 3.32 percentage. Concentration of omega-3 and 6 fatty acids in butter oil can be increased by chia oil. (author)

Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear.

Science.gov (United States)

Zhu, Xiao-Na; Liu, Xian-Dong; Zhuang, Hanyi; Henkemeyer, Mark; Yang, Jing-Yu; Xu, Nan-Jie

2016-09-28

The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase-dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved. Generation of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB-ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal

The Promising Future of Chia, Salvia hispanica L.

OpenAIRE

Mohd Ali, Norlaily; Yeap, Swee Keong; Ho, Wan Yong; Beh, Boon Kee; Tan, Sheau Wei; Tan, Soon Guan

2012-01-01

With increasing public health awareness worldwide, demand for functional food with multiple health benefits has also increased. The use of medicinal food from folk medicine to prevent diseases such as diabetes, obesity, and cardiovascular problems is now gaining momentum among the public. Seed from Salvia hispanica L. or more commonly known as chia is a traditional food in central and southern America. Currently, it is widely consumed for various health benefits especially in maintaining heal...

EFFECT OF CHIA SEED (SALVIA HISPANICA L.) CONSUMPTION ON CARDIOVASCULAR RISK FACTORS IN HUMANS: A SYSTEMATIC REVIEW.

Science.gov (United States)

de Souza Ferreira, Cynthia; dd Sousa Fomes, Lucilia de Fátima; da Silva, Gilze Espirito Santo; Rosa, Glorimar

2015-11-01

chia is a seed rich in such nutrients as proteins, n-3 fatty acids and especially alpha-linolenic acid (ALA), minerals, fibers and antioxidants. Efforts have been made to assess whether human consumption of chia can reduce cardiovascular risk factors; however, it has not been established as effective and the findings of the few studies to have looked into the matter are inconsistent. to systematize the findings of studies assessing the effect the consumption of chia seed, either milled or whole, has in the prevention/control of cardiovascular risk factors in humans. this is a systematic literature review (SLR) with no meta-analysis. The articles scrutinizedwere identified in the electronic databases Lilacs, Medline (Pub- Med version), Cochrane, Scielo, Scopus, and Web of Science under the keywords"dyslipidemia" or "dislipidemia", "hyperlipidemia" or "hiperlipidemia", "obesity" or "obesidade", "salvia"or"salviahispanica", "Lamiaceae" or "chia", "hypertension" or "hipertensão", "hypertrygliceridemia" or "hipertrigliceridemia", and "riscocardiovascular" or "cardiovascularrisk." We chose for our selection English-, Portuguese- or Spanish-language articles about clinical trials on humans and published within the last ten years. The biases of risk analysis were carried out considering 6 of the 8 criteria of the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1. seven studies (n = 200) fit our inclusion criteria. Of the chosen clinical trials, only one was not randomized. Five of the studies were blind experiments. Two of the studies were acute trials, both of them randomized. Of the chia seed interventions, one study showed a significant drop in systolic blood pressure (SBP) and inflammatory markers, yet there was no change in body mass, lipid profile or blood sugar. In four of the studies reviewed there was a significant spike in ALA and eicosapentaenoic acid (EPA), with no significant change to other parameters. In the acute trials, post

Size and receptor density of glutamatergic synapses: a viewpoint from left-right asymmetry of CA3-CA1 connections

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Yoshiaki Shinohara

2009-07-01

Full Text Available Synaptic plasticity is considered to be the main mechanism for learning and memory. Excitatory synapses in the cerebral cortex and hippocampus undergo plastic changes during development and in response to electric stimulation. It is widely accepted that this process is mediated by insertion and elimination of various glutamate receptors. In a series of recent investigations on left-right asymmetry of hippocampal CA3-CA1 synapses, glutamate receptor subunits have been found to have distinctive expression patterns that depend on the postsynaptic density (PSD area. Particularly notable are the GluR1 AMPA receptor subunit and NR2B NMDA receptor subunit, where receptor density has either a supra-linear (GluR1 AMPA or inverse (NR2B NMDAR relationship to the PSD area. We review current understanding of structural and physiological synaptic plasticity and propose a scheme to classify receptor subtypes by their expression pattern with respect to PSD area.

Comparison of flax (Linum usitatissimum) and Salba-chia (Salvia hispanica L.) seeds on postprandial glycemia and satiety in healthy individuals: a randomized, controlled, crossover study.

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Vuksan, V; Choleva, L; Jovanovski, E; Jenkins, A L; Au-Yeung, F; Dias, A G; Ho, H V T; Zurbau, A; Duvnjak, L

2017-02-01

Flax and Salba-chia seeds have risen in popularity owing to their favorable nutrient composition, including a high fiber content. Despite having comparable nutritional profiles, preliminary observations suggest differences in gelling properties, an attribute that may alter the kinetics of food digestion. Thus, we compared the effect of two seeds on postprandial glycemia and satiety scores. Fifteen healthy participants (M/F: 5/10; age: 23.9±3 years; BMI: 22.2±0.8 kg/m 2 ) were randomized to receive a 50 g glucose challenge, alone or supplemented with either 25 g ground Salba-chia or 31.5 g flax, on three separate occasions. Blood glucose samples and satiety ratings were collected at fasting and over 2-h postprandially. In addition, in vitro viscosity of the beverages was assessed utilizing standard rheological methodology. Both Salba-chia and flax reduced blood glucose area under the curve over 120 min by 82.5±19.7 mmol/l (P<0.001) and 60.0±19.7 mmol/l (P=0.014), respectively, relative to a glucose control. Salba-chia reduced peak glucose (-0.64±0.24 mmol/l; P=0.030) and increased time to peak (11.3±3.8 min; P=0.015) compared with flax. Salba-chia significantly reduced the mean ratings of desire to eat (-7±2 mm; P=0.005), prospective consumption (-7±2 mm; P=0.010) and overall appetite score (-6±2 mm; P=0.012), when compared with flax. The viscosity of Salba-chia, flax and control was 49.9, 2.5, and 0.002 Pa·s, respectively. Despite the similarities in nutritional composition, Salba-chia appears to have the ability to convert glucose into a slow-release carbohydrate and affect satiety to a greater extent than flax, possibly due to the higher fiber viscosity. Incorporation of either flax or Salba-chia into the diet may be beneficial, although use of Salba-chia may confer additional benefit.

Influence of Pollen, Chia Seeds and Cranberries Addition on the Physical and Probiotics Characteristics of Yogurt

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Carmen Pop

2015-05-01

Full Text Available Yoghurt is a fermented milk product obtained from fermentation of Lactobacillus bulgaricus and Streptococcus thermophilus strains. The effect of bee pollen, chia seeds and cranberries on the viability of probiotic bacteria in yogurts during storage (21 days at refrigerated temperature (4°C was evaluated. The yogurt supplementation with 1,4 % chia seeds and 7,6% cranberries significantly improves the stability of the lactic acid bacteria, that contained the recommended levels of (106–107 cfu/g probiotic bacteria at the end of 21-day shelf life.

The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.

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Rubio, María E; Matsui, Ko; Fukazawa, Yugo; Kamasawa, Naomi; Harada, Harumi; Itakura, Makoto; Molnár, Elek; Abe, Manabu; Sakimura, Kenji; Shigemoto, Ryuichi

2017-11-01

The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.

Glutamatergic substrates of drug addiction and alcoholism1

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Gass, Justin T.; Foster Olive, M.

2008-01-01

The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and mematine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism. PMID:17706608

Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing

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Rodrigo Valenzuela

2015-08-01

Full Text Available α-Linolenic acid (ALA is the precursor of docosahexaenoic acid (DHA in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L., a plant native to some Latin American countries, is high in ALA (up to 60% and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22–35 years old tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21 and a chia group (n = 19, which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA ingestion, no showing modification of arachidonic acid (AA, eicosapentaenoic acid (EPA and DHA; (ii a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

Omega-3 fatty acids, phenolic compounds and antioxidant characteristics of chia oil supplemented margarine.

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Nadeem, Muhammad; Imran, Muhammad; Taj, Imran; Ajmal, Muhammad; Junaid, Muhammad

2017-05-31

Chia (Salvia hispanica L.) is known as power house of omega fatty acids which has great health benefits. It contains up to 78% linolenic acid (ω-3) and 18% linoleic acid (ω-6), which could be a great source of omega-3 fatty acids for functional foods. Therefore, in this study, margarines were prepared with supplementation of different concentrations of chia oil to enhance omega-3 fatty acids, antioxidant characteristics and oxidative stability of the product. Margarines were formulated from non-hydrogenated palm oil, palm kernel and butter. Margarines were supplemented with 5, 10, 15 and 20% chia oil (T 1 , T 2 , T 3 and T 4 ), respectively. Margarine without any addition of chia oil was kept as control. Margarine samples were stored at 5 °C for a period of 90 days. Physico-chemical (fat, moisture, refractive index, melting point, solid fat index, fatty acids profile, total phenolic contents, DPPH free radical scavenging activity, free fatty acids and peroxide value) and sensory characteristics were studied at the interval of 45 days. The melting point of T 1 , T 2 , T 3 and T 4 developed in current investigation were 34.2, 33.8, 33.1 and 32.5 °C, respectively. The solid fat index of control, T 1 , T 2 , T 3 and T 4 were 47.21, 22.71, 20.33, 18.12 and 16.58%, respectively. The α-linolenic acid contents in T 1 , T 2 , T 3 and T 4 were found 2.92, 5.85, 9.22, 12.29%, respectively. The concentration of eicosanoic acid in T 2 , T 3 and T 4 was 1.82, 3.52, 6.43 and 9.81%, respectively. The content of docosahexanoic acid in T 2 , T 3 and T 4 was present 1.26, 2.64, 3.49 and 5.19%, respectively. The omega-3 fatty acids were not detected in the control sample. Total phenolic contents of control, T 1 , T 2 , T 3 and T 4 samples were 0.27, 2.22, 4.15, 7.23 and 11.42 mg GAE/mL, respectively. DPPH free radical scavenging activity for control, T 1 , T 2 , T 3 and T 4 was noted 65.8, 5.37, 17.82, 24.95, 45.42 and 62.8%, respectively. Chlorogenic acid, caffeic acid

Survival of Salmonella during Production of Partially Sprouted Pumpkin, Sunflower, and Chia Seeds Dried for Direct Consumption.

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Keller, Susanne E; Anderson, Nathan M; Wang, Can; Burbick, Stephen J; Hildebrandt, Ian M; Gonsalves, Lauren J; Suehr, Quincy J; Farakos, Sofia M Santillana

2018-04-01

Ready-to-eat foods based on dried partially sprouted seeds have been associated with foodborne salmonellosis. Whereas research has focused on the potential for Salmonella initially present in or on seeds to grow and survive during fresh sprout production, little is known about the potential for growth and survival of Salmonella associated with seeds that have been partially sprouted and dried. The goal of this study was to determine the growth of Salmonella during soaking for partial germination of pumpkin, sunflower, and chia seeds and subsequent survival during drying and storage. Pumpkin, sunflower, and chia seeds were inoculated with a four-serotype Salmonella cocktail by the dry transfer method and were soaked in sterile water at 25 or 37°C for 24 h. During the soaking period, Salmonella exhibited growth rates of 0.37 ± 0.26, 0.27 ± 0.12, and 0.45 ± 0.19 log CFU/h at 25°C and 0.94 ± 0.44, 1.04 ± 0.84, and 0.73 ± 0.36 log CFU/h at 37°C for chia, pumpkin, and sunflower seeds, respectively. Soaked seeds were drained and dried at 25, 51, and 60°C. Drying resulted in >5 log CFU/g loss at both 51 and 60°C and ∼3 log CFU/g loss at 25°C on partially sprouted pumpkin and sunflower seeds. There was no decrease in Salmonella during drying of chia seeds at 25°C, and only drying at 60°C provided losses >5 log CFU/g. Dried seeds were stored at 37 and 45°C at 15 and 76% relative humidity (RH) levels. The combination of temperature and RH exerted a stronger effect than either factor alone, such that rates at which Salmonella decreased generally followed this order: 37°C at 15% RH < 45°C at 15% RH < 37°C at 76% RH < 45°C at 76% RH for all seeds tested. Rates differed based on seed type, with chia seeds and chia seed powder having the smallest rate of Salmonella decrease, followed by sunflower and pumpkin seeds. Drying at higher temperatures (50 and 61°C) or storing at elevated temperature and humidity (45°C and 76% RH) resulted in significantly different

Study on elemental features of Longquan celadon at Fengdongyan kiln site in Yuan and Ming Dynasties by EDXRF

Energy Technology Data Exchange (ETDEWEB)

Li, L. [Key Laboratory of Nuclear Analysis Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China); Feng, S.L., E-mail: fengsl@ihep.ac.cn [Key Laboratory of Nuclear Analysis Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China); Feng, X.Q.; Xu, Q.; Yan, L.T.; Ma, B.; Liu, L. [Key Laboratory of Nuclear Analysis Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China)

2012-12-01

The energy dispersive X-ray fluorescence (EDXRF) is used to determine the chemical compositions of Longquan celadon body and glaze at Fengdongyan kiln in Yuan and Ming Dynasties. In order to analyze the elemental features in different cultural periods, 196 typical Longquan celadon shards are selected including the Early Yuan (EY), the Middle and Late Yuan (MLY), the Early Ming (EM) and the Middle Ming (MM) periods. The results indicate that the contents of K{sub 2}O, CaO, TiO{sub 2} and Fe{sub 2}O{sub 3} for celadon body and glaze are various in different cultural periods. The b values b=RO/(RO+R{sub 2}O), RO represents for alkali-earth metal elements and R{sub 2}O stands for alkali metal elements) show that the glazes of Longquan celadon in Yuan and Ming Dynasties belong to the category of calcium-alkali glaze. The principal component analysis (PCA) exhibits that the raw materials used for body and glaze in four periods have the inheritance relation. The only difference is that the raw materials for glaze in MM period were similar to those in EM period. The producing and firing technology of Longquan celadon had reached a higher level in the Early Ming Dynasty.

Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

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Perea, Gertrudis; Gómez, Ricardo; Mederos, Sara; Covelo, Ana; Ballesteros, Jesús J; Schlosser, Laura; Hernández-Vivanco, Alicia; Martín-Fernández, Mario; Quintana, Ruth; Rayan, Abdelrahman; Díez, Adolfo; Fuenzalida, Marco; Agarwal, Amit; Bergles, Dwight E; Bettler, Bernhard; Manahan-Vaughan, Denise; Martín, Eduardo D; Kirchhoff, Frank; Araque, Alfonso

2016-12-24

Interneurons are critical for proper neural network function and can activate Ca 2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABA A receptors, potentiation involved astrocyte GABA B receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABA B receptor ( Gabbr1 ) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

Effect of the addition of chia's by-product on the composition of fatty acids in hamburgers through chemometric methods.

Science.gov (United States)

Souza, Aloisio H P; Gohara, Aline K; Rotta, Eliza M; Chaves, Marcia A; Silva, Claudia M; Dias, Lucia F; Gomes, Sandra T M; Souza, Nilson E; Matsushita, Makoto

2015-03-30

Hamburger is a meat-based food that is easy to prepare and is widely consumed. It can be enriched using different ingredients, such as chia's by-product, which is rich in omega-3. Chemometrics is a very interesting tool to assess the influence of ingredients in the composition of foods. A complete factorial design 2(2) (two factors in two levels) with duplicate was performed to investigate the influence of the factors (1) concentration of textured soy proteins (TSP) and (2) concentration of chia flour partially defatted (CFPD) as a partial replacement for the bovine meat and porcine fat mix in hamburgers. The results of proximal composition, lipid oxidation, fatty acids sums, ratios, and nutritional indexes were used to propose statistical models. The factors TSP and CFPD were significant, and the increased values contributed to improve the composition in fatty acids, crude protein, and ash. Principal components analysis distinguished the samples with a higher content of chia. In desirability analysis, the highest level of TSP and CFPD was described as the optimal region, and it was not necessary to make another experimental point. The addition of chia's by-product is an alternative to increase the α-linolenic contents and to obtain nutritionally balanced food. © 2014 Society of Chemical Industry.

Omega-3 fatty acids and oxidative stability of ice cream supplemented with olein fraction of chia (Salvia hispanica L.) oil.

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Ullah, Rahman; Nadeem, Muhammad; Imran, Muhammad

2017-02-07

Chia (Salvia hispanica L.) has been regarded as good source of polyunsaturated omega-3 fatty acids with cardiac, hepatic, hypotensive, antiallergic and antidiabetic role. Concentration of omega-3 fatty acids in chia oil can be enhanced by fractionation. Olein/low melting fraction of chia oil has higher concentration of omega-3 fatty acids. Therefore, main objective of current investigation was determination of various concentration effect of olein fraction of chia oil on omega-3 fatty acids, oxidative stability and sensory characteristics of ice cream. Ice cream samples were prepared by partially replacing the milk fat with olein fraction of chia oil at 5, 10, 15 and 20% concentrations (T 1 , T 2 , T 3 and T 4 ), respectively. Ice cream prepared from 100% milk fat was kept as control. Ice cream samples stored at -18 °C for 60 days were analysed at 0, 30 and 60 days of the storage period. Fatty acid profile, total phenolic contents, total flavonoids, free fatty acids, peroxide value, anisidine value and sensory characteristics of ice cream samples was studied. Concentration of α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid in T 4 was 13.24, 0.58, 0.42 and 0.31%, respectively. Total phenolic contents of control, T 1 , T 2 , T 3 and T 4 were recorded 0.12, 1.65, 3.17, 5.19 and 7.48 mg GAE/mL, respectively. Total flavonoid content of control, T 1 , T 2 , T 3 and T 4 were found 0.08, 0.64, 1.87, 3.16 and 4.29 mg Quercetin Equivalent/mL. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity of control, T 1 , T 2 , T 3 and T 4 was noted 5.61, 17.43, 36.84, 51.17 and 74.91%, respectively. After 60 days of storage period, the highest peroxide value of 1.84 (MeqO 2 /kg) was observed in T 4 , which was much less than allowable limit of 10 (MeqO 2 /kg). Flavour score was non-significant after 30 days of storage period. Supplementation of ice cream with olein fraction of chia oil enhanced the concentration of

The Antimicrobial Activity of the Essential Oil of Pistacia lentiscus var. Chia

NARCIS (Netherlands)

Gkogka, E.; Hazeleger, W.C.; Posthumus, M.A.; Beumer, R.R.

2013-01-01

The essential oil of the resin of Pistacia lentiscus var. Chia (mastic oil) was studied in vitro against a wide range of foodborne pathogenic and spoilage microorganisms with a diffusion and a dilution method. Furthermore its chemical composition was analyzed by means of Gas Chromatography-Mass

Imaging the glutamatergic system in vivo - relevance to schizophrenia

Energy Technology Data Exchange (ETDEWEB)

Bressan, R.A.; Pilowsky, L.S. [Inst. of Psychiatry, London (United Kingdom); Inst. of Nuclear Medicine, University College of London Medical School (United Kingdom)

2000-11-01

Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system. (orig.)

Imaging the glutamatergic system in vivo - relevance to schizophrenia

International Nuclear Information System (INIS)

Bressan, R.A.; Pilowsky, L.S.

2000-01-01

Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system. (orig.)

Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication.

Science.gov (United States)

Rozanski, Gabriela M; Li, Qi; Stanley, Elise F

2013-04-01

The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS-glial cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transglial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 receptor. Isolated DRG cell clusters exhibited daisy-chain and branching NS-glial cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the glial-to-neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus.

Science.gov (United States)

Naylor, David E; Liu, Hantao; Niquet, Jerome; Wasterlain, Claude G

2013-06-01

After 1h of lithium-pilocarpine status epilepticus (SE), immunocytochemical labeling of NMDA receptor NR1 subunits reveals relocation of subunits from the interior to the cell surface of dentate gyrus granule cells and CA3 pyramidal cells. Simultaneously, an increase in NMDA-miniature excitatory postsynaptic currents (mEPSC) as well as an increase in NMDA receptor-mediated tonic currents is observed in hippocampal slices after SE. Mean-variance analysis of NMDA-mEPSCs estimates that the number of functional postsynaptic NMDA receptors per synapse increases 38% during SE, and antagonism by ifenprodil suggests that an increase in the surface representation of NR2B-containing NMDA receptors is responsible for the augmentation of both the phasic and tonic excitatory currents with SE. These results provide a potential mechanism for an enhancement of glutamatergic excitation that maintains SE and may contribute to excitotoxic injury during SE. Therapies that directly antagonize NMDA receptors may be a useful therapeutic strategy during refractory SE. Copyright © 2013 Elsevier Inc. All rights reserved.

The Vibrio cholerae Extracellular Chitinase ChiA2 Is Important for Survival and Pathogenesis in the Host Intestine

Science.gov (United States)

Mondal, Moumita; Nag, Dhrubajyoti; Koley, Hemanta; Saha, Dhira Rani; Chatterjee, Nabendu Sekhar

2014-01-01

In aquatic environments, Vibrio cholerae colonizes mainly on the chitinous surface of copepods and utilizes chitin as the sole carbon and nitrogen source. Of the two extracellular chitinases essential for chitin utilization, the expression of chiA2 is maximally up-regulated in host intestine. Recent studies indicate that several bacterial chitinases may be involved in host pathogenesis. However, the role of V. cholerae chitinases in host infection is not yet known. In this study, we provide evidence to show that ChiA2 is important for V. cholerae survival in intestine as well as in pathogenesis. We demonstrate that ChiA2 de-glycosylates mucin and releases reducing sugars like GlcNAc and its oligomers. Deglycosylation of mucin corroborated with reduced uptake of alcian blue stain by ChiA2 treated mucin. Next, we show that V. cholerae could utilize mucin as a nutrient source. In comparison to the wild type strain, ΔchiA2 mutant was 60-fold less efficient in growth in mucin supplemented minimal media and was also ∼6-fold less competent to survive when grown in the presence of mucin-secreting human intestinal HT29 epithelial cells. Similar results were also obtained when the strains were infected in mice intestine. Infection with the ΔchiA2 mutant caused ∼50-fold less fluid accumulation in infant mice as well as in rabbit ileal loop compared to the wild type strain. To see if the difference in survival of the ΔchiA2 mutant and wild type V. cholerae was due to reduced adhesion of the mutant, we monitored binding of the strains on HT29 cells. The initial binding of the wild type and mutant strain was similar. Collectively these data suggest that ChiA2 secreted by V. cholerae in the intestine hydrolyzed intestinal mucin to release GlcNAc, and the released sugar is successfully utilized by V. cholerae for growth and survival in the host intestine. PMID:25244128

Heaths and forests of the western hills of Chia, Bogota savanna, Colombia

International Nuclear Information System (INIS)

Cortes S, Sandra P.; Van der Hammen, Thomas; Rangel Ch, J Orlando

2000-01-01

The authors make a study of the heaths and forests of the western hills of the population of Chia, located in the savanna of Bogota and the presence or absences of these in the same Bogota savanna; the authors treat topics like their physiognomy and composition, distribution and ecology among other topics

Un ente innovativo di ricerca e di servizi per la informazione geospaziale: GIS Research Center della Feng-Chia University di Taiwan (GIS.FCU

Directory of Open Access Journals (Sweden)

Mauro Salvemini

2012-04-01

Full Text Available La storia di un Laboratorio GIS a Taiwan nato da un accordo tra Feng-Chia University e la Università di Roma “LaSapienza” oggi tra i primi nel mondo nel settore dell’informazione geospaziale per la ricerca nell’ambito dei testdell’interoperabilità. A body of research and innovative services for geospatial infor-mation: GIS Research Center of Feng-Chia University in Taiwan (GIS.FCU The story of a GIS laboratory in Taiwan born on an agreement between the Feng-Chia University and the University of Rome "La Sapienza" now among the first in the world in the field of information for research for geospatial application.

Metabotropic glutamatergic receptors and their ligands in drug addiction.

Science.gov (United States)

Pomierny-Chamioło, Lucyna; Rup, Kinga; Pomierny, Bartosz; Niedzielska, Ewa; Kalivas, Peter W; Filip, Małgorzata

2014-06-01

Glutamatergic excitatory transmission is implicated in physiological and pathological conditions like learning, memory, neuronal plasticity and emotions, while glutamatergic abnormalities are reported in numerous neurological and psychiatric disorders, including neurodegenerative diseases, epilepsy, stroke, traumatic brain injury, depression, anxiety, schizophrenia and pain. Also, several lines of evidence have accumulated indicating a pivotal role for glutamatergic neurotransmission in mediating addictive behaviors. Among the proteins regulating glutamatergic transmission, the metabotropic glutamate receptors (mGluR) are being developed as pharmacological targets for treating many neuropsychiatric disorders, including drug addiction. In this review we describe the molecular structure of mGluRs and their distribution, physiology and pharmacology in the central nervous system, as well as their use as targets in preclinical studies of drug addiction. Copyright © 2013 Elsevier Inc. All rights reserved.

Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons

DEFF Research Database (Denmark)

Leão, Richardson N.; Colom, Luis V.; Borgius, Lotta

2012-01-01

(MS) neurons in mice. In glutamatergic neurons Aβ increases firing frequency and blocks the A- and the M-current (IA and IM, respectively). While the IA block is similar in other MS neuron classes, the block of IM is specific to glutamatergic neurons. IM block and a simulated Aβ block mimic the Aβ......-induced increase in spontaneous firing in glutamatergic neurons. Calcium imaging shows that under control conditions glutamatergic neurons rarely fire while nonglutamatergic neurons fire coherently at theta frequencies. Aβ increases the firing rate of glutamatergic neurons while nonglutamatergic neurons lose theta...... firing coherence. Our results demonstrate that Aβ-induced dysfunction of glutamatergic neurons via IM decrease diminishes MS rhythmicity, which may negatively affect hippocampal rhythmogenesis and underlie the memory loss observed in Alzheimer's disease....

Role of the origin of glutamatergic synaptic inputs in controlling synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

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Gilles Erwann Martin

2015-07-01

Full Text Available It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens, a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the nucleus accumbens receives glutamatergic inputs from distinct brain regions (e.g. the prefrontal cortex, the amygdala and the hippocampus, each region providing different information (e.g. spatial, emotional and cognitive. Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD and long-term potentiation (tLTP and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute EtOH has little effects on higher order information coming from the prefrontal cortex (PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

Influences of chia flour and the concentration of total solids on the characteristics of ‘dulce de leche’ from goat milk

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Marcia Alves CHAVES

2018-03-01

Full Text Available Abstract A factorial categorical design totalling six treatments was applied to investigate the influence of the substitution of corn starch with whole and partially defatted chia flour under the technical characteristics (centesimal composition, instrumental analyses, and sensory evaluation and nutritional disorders (composition of fatty acids and index of the nutritional quality of the lipid fraction of ‘dulce de leche’ concentrated to 72 and 78 °B. The treatments with chia flour concentrated to 72 °B showed higher moisture content and lower compression force, and when the concentration range increased to 78 °B, the levels of total lipids amounted up to 1.40 times when compared to treatment with corn starch. The polyunsaturated fatty acids, particularly omega-3 and omega-6 levels, were higher in treatments with chia flour on both tracks of concentration, allowing a reduction in the atherogenic index and thrombogenic index effects and the n-6/n-3 ratio. The treatments of ‘dulce de leche’ with a lower concentration of soluble solids obtained greater acceptance and consumer purchase intention. The application of whole chia flour in small proportions and in the concentration of 72 °B was the most appropriate under the studied conditions, showing improvement in the nutritional quality and with good technical aspects of candy made with goat milk.

Salba-chia (Salvia hispanica L.) in the treatment of overweight and obese patients with type 2 diabetes: A double-blind randomized controlled trial.

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Vuksan, V; Jenkins, A L; Brissette, C; Choleva, L; Jovanovski, E; Gibbs, A L; Bazinet, R P; Au-Yeung, F; Zurbau, A; Ho, H V T; Duvnjak, L; Sievenpiper, J L; Josse, R G; Hanna, A

2017-02-01

Preliminary findings indicate that consumption of Salba-chia (Salvia hispanica L.), an ancient seed, improves management of type 2 diabetes and suppresses appetite. The aim of this study was to assesse the effect of Salba-chia on body weight, visceral obesity and obesity-related risk factors in overweight and obese adults with type 2 diabetes. A double-blind, randomized, controlled trial with two parallel groups involved 77 overweight or obese patients with type 2 diabetes (HbA 1c : 6.5-8.0%; BMI: 25-40 kg/m 2 ). Both groups followed a 6-month calorie-restricted diet; one group received 30 g/1000 kcal/day of Salba-chia, the other 36 g/1000 kcal/day of an oat bran-based control. Primary endpoint was change in body weight over 6-months. Secondary endpoints included changes in waist circumference, body composition, glycemic control, C-reactive protein, and obesity-related satiety hormones. At 6-months, participants on Salba-chia had lost more weight than those on control (1.9 ± 0.5 kg and 0.3 ± 0.4 kg, respectively; P = 0.020), accompanied by a greater reduction in waist circumference (3.5 ± 0.7 cm and 1.1 ± 0.7 cm, respectively; P = 0.027). C-reactive protein was reduced by 1.1 ± 0.5 mg/L (39 ± 17%) on Salba-chia, compared to 0.2 ± 0.4 mg/L (7 ± 20%) on control (P = 0.045). Plasma adiponectin on the test intervention increased by 6.5 ± 0.7%, with no change observed on control (P = 0.022). The results of this study, support the beneficial role of Salba-chia seeds in promoting weight loss and improvements of obesity related risk factors, while maintaining good glycemic control. Supplementation of Salba-chia may be a useful dietary addition to conventional therapy in the management of obesity in diabetes. REGISTRATION: clinicaltrials.gov identifier: NCT01403571. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the

Study on the property of the production for Fengdongyan kiln in Early Ming dynasty by INAA and EDXRF

International Nuclear Information System (INIS)

Li, L.; Huang, Y.; Sun, H.Y.; Yan, L.T.; Feng, S.L.; Xu, Q.; Feng, X.Q.

2016-01-01

A lot of official wares carved “Guan” or the dragon patterns were excavated on the strata of Ming dynasty of the Fengdongyan kiln site at Dayao County. The imperial porcelain was fired in Hongwu and Yongle eras. However, the emergence of this imperial porcelain has triggered academic debate about the property of Fengdongyan kiln in the Early Ming dynasty. Based on the differences of the official kiln management, some scholars have determined that the property of the production for this kiln was the civilian kiln. According to the historical textural records and typology, others preliminary confirmed that Fengdongyan kiln was the official kiln. In this paper, the elemental compositions of body and glaze in imperial and civilian porcelain are study by INAA and EDXRF for determining the property of the production for this kiln in Early Ming dynasty. After the processing of experimental data by geochemical analysis and principal component analysis, the result show that the raw materials for making body and glaze in imperial porcelain are similar with those of the civilian porcelain and the degrees of elutriation for body can be slightly different in HW-M period of Ming dynasty. The analytical results support the view that the Fengdongyan kiln is civilian not official.

Study on the property of the production for Fengdongyan kiln in Early Ming dynasty by INAA and EDXRF

Energy Technology Data Exchange (ETDEWEB)

Li, L. [Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China); Huang, Y.; Sun, H.Y. [Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China); University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049 (China); Yan, L.T.; Feng, S.L.; Xu, Q. [Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China); Feng, X.Q., E-mail: fengxq@ihep.ac.cn [Institute of High Energy Physics, Chinese Academy of Sciences, 19 Yu Quan Lu, Beijing 100049 (China)

2016-08-15

A lot of official wares carved “Guan” or the dragon patterns were excavated on the strata of Ming dynasty of the Fengdongyan kiln site at Dayao County. The imperial porcelain was fired in Hongwu and Yongle eras. However, the emergence of this imperial porcelain has triggered academic debate about the property of Fengdongyan kiln in the Early Ming dynasty. Based on the differences of the official kiln management, some scholars have determined that the property of the production for this kiln was the civilian kiln. According to the historical textural records and typology, others preliminary confirmed that Fengdongyan kiln was the official kiln. In this paper, the elemental compositions of body and glaze in imperial and civilian porcelain are study by INAA and EDXRF for determining the property of the production for this kiln in Early Ming dynasty. After the processing of experimental data by geochemical analysis and principal component analysis, the result show that the raw materials for making body and glaze in imperial porcelain are similar with those of the civilian porcelain and the degrees of elutriation for body can be slightly different in HW-M period of Ming dynasty. The analytical results support the view that the Fengdongyan kiln is civilian not official.

Development of gluten-free bread using tartary buckwheat and chia flour rich in flavonoids and omega-3 fatty acids as ingredients.

Science.gov (United States)

Costantini, Lara; Lukšič, Lea; Molinari, Romina; Kreft, Ivan; Bonafaccia, Giovanni; Manzi, Laura; Merendino, Nicolò

2014-12-15

In this study, chia seed flour, which is rich in omega-3 alpha-linolenic acid, and common and tartary buckwheat flour, which has a high antioxidant activity, were integrated into different types of bread with the aim of improving their nutritional value and healthy features. Our results indicate that bread made with chia and tartary buckwheat flour was more acceptable in many nutritional aspects compared to the control (common wheat bread); it contained a higher amount of protein (20%), insoluble dietary fibres (74%), ash (51%), and alpha-linolenic acid (67.4%). Moreover, this bread possessed lower energy (14%) and carbohydrate contents (24%) compared to the control. Tartary buckwheat also improved the total antioxidant capacity of the bread (about 75%) and provided a considerable amount of flavonoids, which are healthy non-nutritional compounds. Overall, chia and tartary buckwheat represent excellent raw materials for the formulation of gluten-free bread with high nutritional value. Copyright © 2014 Elsevier Ltd. All rights reserved.

On-chip photonic synapse.

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Cheng, Zengguang; Ríos, Carlos; Pernice, Wolfram H P; Wright, C David; Bhaskaran, Harish

2017-09-01

The search for new "neuromorphic computing" architectures that mimic the brain's approach to simultaneous processing and storage of information is intense. Because, in real brains, neuronal synapses outnumber neurons by many orders of magnitude, the realization of hardware devices mimicking the functionality of a synapse is a first and essential step in such a search. We report the development of such a hardware synapse, implemented entirely in the optical domain via a photonic integrated-circuit approach. Using purely optical means brings the benefits of ultrafast operation speed, virtually unlimited bandwidth, and no electrical interconnect power losses. Our synapse uses phase-change materials combined with integrated silicon nitride waveguides. Crucially, we can randomly set the synaptic weight simply by varying the number of optical pulses sent down the waveguide, delivering an incredibly simple yet powerful approach that heralds systems with a continuously variable synaptic plasticity resembling the true analog nature of biological synapses.

The immunological synapse

DEFF Research Database (Denmark)

Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

2003-01-01

. A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...

[Analysis of Xin'an imperial medical officials in the Ming and Qing Dynasties].

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Wan, S M; Liu, B S; Lu, X

2017-01-28

Xin'an imperial medical officials of the Ming and Qing Dynasties was a special group of Xin'an doctors. It had exerted a positive and active impact on the development of traditional Chinese medicine. Rooted in the Xin'an region, with higher literacy and noble medical ethics and medical knowhow, through the imperial enlistment, examination, and other ways to enter the palace as imperial medical officials. During their tenure, they wrote books and communicated and merged with the folk medicine actively. After retiring, they were still involved actively in folk medicine activities, thus promoting and influencing the development of local medicine. The formation of Xin'an community of imperial medical officials in the Ming and Qing Dynasties was closely related to the prosperity of regional culture and commerce, and the development of medicine in Xin'an region.

Network Intrusion Dataset Assessment

Science.gov (United States)

2013-03-01

International Conference on Computational Intelligence and Natural Computing, volume 2, pages 413–416, June 2009. • Rung Ching Chen, Kai -Fan Cheng, and...Chia-Fen Hsieh . “Using rough set and support vector machine for network intrusion detection.” International Journal of Network Security & Its...intrusion detection using FP tree rules.” Journal Of Advanced Networking and Applications, 1(1):30–39, 2009. • Ming-Yang Su, Gwo-Jong Yu , and Chun-Yuen

The Images of Jesus in the Emergence of Christian Spirituality in Ming and Qing China

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Xiaobai Chu

2016-03-01

Full Text Available Images of Jesus Christ played an important role in the emergence of Christian spirituality in Ming and Qing China. Of the great many images that we know from this period, this paper introduces five of them: Jesus as infant, criminal, gate, brother, and pig. The paper unfolds the historical, anthropological, and theological layers of these images to reveal the original tension between Christian spirituality and Chinese culture. The central thesis of the paper therefore is that this tension is reflected in the images of Jesus Christ and, moreover, that analyzing this tension allows us to achieve a more profound understanding of the emergence of Christian spirituality in Ming, Qing, and perhaps even today’s China.

Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

Science.gov (United States)

Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

2017-01-01

The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

Glutamatergic system abnormalities in posttraumatic stress disorder.

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Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Matsuoka, Yutaka

2015-12-01

Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity. We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD). This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses. Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07). These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.

Wireless synapses in bio-inspired neural networks

Science.gov (United States)

Jannson, Tomasz; Forrester, Thomas; Degrood, Kevin

2009-05-01

Wireless (virtual) synapses represent a novel approach to bio-inspired neural networks that follow the infrastructure of the biological brain, except that biological (physical) synapses are replaced by virtual ones based on cellular telephony modeling. Such synapses are of two types: intracluster synapses are based on IR wireless ones, while intercluster synapses are based on RF wireless ones. Such synapses have three unique features, atypical of conventional artificial ones: very high parallelism (close to that of the human brain), very high reconfigurability (easy to kill and to create), and very high plasticity (easy to modify or upgrade). In this paper we analyze the general concept of wireless synapses with special emphasis on RF wireless synapses. Also, biological mammalian (vertebrate) neural models are discussed for comparison, and a novel neural lensing effect is discussed in detail.

A recombinant Anticarsia gemmatalis MNPV harboring chiA and v-cath genes from Choristoneura fumiferana defective NPV induce host liquefaction and increased insecticidal activity.

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Anabele Azevedo Lima

Full Text Available One of the interesting features of Anticarsia gemmatalis multiple nucleopolyhedrovirus isolate 2D (AgMNPV-2D genome is the absence of chitinase (chiA and cathepsin (v-cath genes. This characteristic may be responsible for the lack of liquefaction and melanization in A. gemmatalis larvae killed by AgMNPV-2D infection. This study aimed to test the hypothesis that CHIA and V-CATH proteins from Choristonera fumiferana DEF multiple nucleopolyhedrovirus (CfDEFNPV are able to liquefy and melanize the cuticle of A. gemmatalis larvae infected by a recombinant AgMNPV containing chiA and v-cath genes inserted in its genome. A fragment from the CfDefNPV genome containing chiA and v-cath genes was inserted into the genome of AgMNPV-2D. The recombinant virus (vAgp2100Cf.chiA/v-cath was purified and used to infect insect cells and larvae. Transcripts of v-cath and chiA genes were detected along the infection of insect cells by qRT-PCR, from early to late phases of infection. The analysis of A. gemmatalis larvae killed by vAgp2100Cf.chiA/v-cath infection confirmed the hypothesis proposed. The vAgp2100Cf.chiA/v-cath showed higher insecticidal activity against third instar A. gemmatalis larvae when compared to AgMNPV-2D. The mean time to death was also lower for the vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D at 10 days post infection. Occlusion body production was higher in A. gemmatalis larvae infected with vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D. Enzyme assays showed higher chitinase and cysteine protease activities in insect cells and insects infected with vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D. The introduction of chiA and v-cath genes into the genome of AgMNPV improves its insecticidal activity against A. gemmatalis larvae and this recombinant virus could be used as an alternative to the wild type virus to control this important insect pest.

IEOH MING PEI: UNA IDEA, TRES VARIACIONES / Ieoh Ming Pei: one idea, three variations

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Alberto Donaire Rodríguez

2010-05-01

Full Text Available RESUMENEl texto siguiente es un resumen de mi lección de despedida, el 18 de noviembre de 2006, al jubilarme en la Escuela de Arquitectura de Sevilla. Como no se grabó y nunca llevo escritas mis clases, ésta es una reconstrucción basada en mi guión y en las notas tomadas por algunos asistentes, a los que agradezco su interés. Por vez primera se celebraba en la Escuela un acto de esta naturaleza, por iniciativa del entonces Director, Jaime Navarro Casas. A él agradezco su presencia y sus palabras, e igualmente a Juan Luis Trillo de Leyva, que hizo una especie de recorrido sentimental de mi paso por la Escuela, que escuché con emoción. En el mismo curso dieron luego su lección de despedida dos profesores que han dejado en nosotros honda huella, Rafael Manzano y José Luis Manzanares. Estos actos son un bello colofón de una carrera académica. La clase fue una reflexión sobre la arquitectura, al hilo del comentario de tres obras del arquitecto Ieoh Ming Pei en tres ciudades diferentes: las ampliaciones de la National Gallery de Washington, del Museo del Louvre de París y del Deutsches Historisches Museum de Berlín. SUMMARYThe following text is a summary of my valedictory lecture, on 18 November 2006, on my retirement from the School of Architecture of Seville. As it was not recorded, and my never having written up my classes, this is a reconstruction based on my outline and the notes taken by some of those present, whom I thank for their interest. This was the first time an act of this nature was held in the School, on the initiative of the then Director, Jaime Navarro Casas. I thank him for his presence and his words, and also Juan Luis Trillo de Leyva, who made a sort of sentimental journey of my time at the School, to which I listened with emotion. Later, valedictory lectures were given by two teachers who have left a profound imprint on us, Rafael Manzano and José Luis Manzanares. These acts are a beautiful conclusion to an

Spray dried microparticles of chia oil using emulsion stabilized by whey protein concentrate and pectin by electrostatic deposition.

Science.gov (United States)

Noello, C; Carvalho, A G S; Silva, V M; Hubinger, M D

2016-11-01

Chia seed oil has a high content of α-linolenic acid (60%) and linoleic acid (20%). Use of this oil in different products is limited due to its liquid state, and the presence of insaturation is a trigger for oxidation. In this context, to facilitate the incorporation of chia oil in food products and increase its protection against oxidation, the aim of this work was to produce chia oil microparticles by spray drying using emulsions stabilized by whey protein concentrate (ζ-potential +13.4 at pH3.8) and pectin (ζ-potential -40.4 at pH3.8) through the electrostatic layer-by-layer deposition technique and emulsions prepared with only whey protein concentrate. Emulsions stabilized by whey protein concentrate and stabilized by whey protein concentrate-pectin were prepared using maltodextrin (10 DE) and modified starch (Hi-Cap® 100). They were characterized in relation to stability, droplet size, ζ-Potential and optical microscopy. The microparticles were characterized in relation to moisture content, water activity, particle size, microstructure and oxidative stability by the Rancimat method. Emulsions stabilized by whey protein concentrate-pectin with added maltodextrin 10 DE and emulsions stabilized by whey protein concentrate with added modified starch (Hi-Cap® 100) were stable after 24h. Emulsions stabilized by whey protein concentrate and by whey protein concentrate-pectin showed droplets with mean diameter ranging from 0.80 to 1.31μm, respectively and ζ-potential varying from -6.9 to -27.43mV, respectively. After spray drying, the microparticles showed an mean diameter ranging from 7.00 to 9.00μm. All samples presented high encapsulation efficiency values, above 99%. Microparticles produced with modified starch showed a smoother spherical surface than particles with maltodextrin 10 DE, which presented a wrinkled surface. All microparticles exhibited higher oxidative stability than chia oil in pure form. Copyright © 2016 Elsevier Ltd. All rights reserved.

GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

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Leire Reguero

Full Text Available BACKGROUND: Type-1 cannabinoid receptors (CB(1R are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH that participates in homeostatic and behavioral functions including food intake. Although CB(1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB(1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB(1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. METHODOLOGY/PRINCIPAL FINDINGS: Light and electron microscopy techniques were used to analyze CB(1R distribution in the VMH of CB(1R-WT, CB(1R-KO and conditional mutant mice bearing a selective deletion of CB(1R in cortical glutamatergic (Glu-CB(1R-KO or GABAergic neurons (GABA-CB(1R-KO. At light microscopy, CB(1R immunolabeling was observed in the VMH of CB(1R-WT and Glu-CB(1R-KO animals, being remarkably reduced in GABA-CB(1R-KO mice. In the electron microscope, CB(1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB(1R immunopositive profiles and CB(1R density in terminals making asymmetric or symmetric synapses in CB(1R-WT mice. Furthermore, the proportion of CB(1R immunopositive terminals/preterminals in CB(1R-WT and Glu-CB(1R-KO mice was reduced in GABA-CB(1R-KO mutants. CB(1R density was similar in all animal conditions. Finally, the percentage of CB(1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB(1R-KO mutants relative to CB(1R-WT mice, indicating that CB(1R was distributed in cortical and subcortical excitatory synaptic terminals. CONCLUSIONS/SIGNIFICANCE: Our anatomical results support the idea that the VMH is a relevant hub candidate in

Background Materials on Ching Ming Festival [And] Winter Festival [And] Dragon Boat Festival.

Science.gov (United States)

Lew, Helene

This publication contains three background papers on Chinese festivals which are still celebrated by Chinese Americans. The first festival discussed--Ching Ming--is a celebration of the coming of spring and the occasion of the first outing of the year. This paper discusses the historical development of the festival since prehistoric times,…

Micro SR-XRF analysis on underglaze copper red porcelain of ming dynasty

International Nuclear Information System (INIS)

Guan Li; Zhu Jian; Yang Yimin; Fan Changsheng; Chen Dongliang; Xu Wei; Zhang Jing; Wang Lihua

2013-01-01

Background: The firing techniques of producing underglaze copper red porcelain emerged in the Yuan dynasty and reached its maturity during the Ming and Qing Dynasties in Jingdezhen city. The technique of producing underglaze red porcelain was sensitive to the firing temperature and atmosphere, so it was very hard to produce and also difficult to display red color under the surface successfully. Purpose and Methods: The micro SR-XRF technique was employed to analysis a piece of sherd of underglaze copper red porcelain of early Ming dynasty. The Chemical compositions of glaze and color areas were presented, and the elemental contents in different color areas were obtained by using line-scanning techniques. Results: Some elements such as As and Pb were contained in raw materials, and the content of Cu had obviously increased with the color changing from gray to red. The results indicated that the nature mineral possibly used as the pigment for underglazed copper red porcelain coloration, and the color appearance also depends on the amount of copper in the pigments contained. Conclusions: This paper presents the advantage of the synchrotron radiation XRF technology and contributes to the science evidences for the Chinese ancient porcelain handcraft research. (authors)

Prevention of Noise Damage to Cochlear Synapses

Science.gov (United States)

2017-10-01

Assessment of synapse regeneration : Twelve week old CBA/CaJ mice are exposed to a moderate noise that destroys synapses on inner hair cells (IHCs) but spares...result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells . Excitotoxic trauma damages the postsynaptic cell by...components ............................................. 12 d) Quantitative analysis of effects of neurotrophic factors on synapse regeneration in vitro

Neuromodulation of reciprocal glutamatergic inhibition between antagonistic motoneurons by 5-hydroxytryptamine (5-HT) in crayfish walking system.

Science.gov (United States)

Pearlstein, E; Clarac, F; Cattaert, D

1998-01-23

In an in vitro preparation of the crayfish thoracic locomotor system, paired intracellular recordings were performed from antagonistic depressor (Dep) and levator (Lev) motoneurons (MNs) that control the second joint of walking legs. Connections between these two groups of MNs consist mainly of inhibitory connections and weak electrotonic synapses. Injection of depolarizing current into a Lev MN results in a hyperpolarization in a Dep MN, and vice versa. This reciprocal glutamatergic inhibition, is not changed in the presence of the sodium channel blocker tetrodotoxin (TTX) and therefore is likely supported by a direct connection between MNs. By contrast, reciprocal inhibition is largely reduced in the presence of 5-hydroxytryptamine (5-HT; 10 microM). Direct micro-application of glutamate pressure-ejected close to an intracellularly recorded MN, evoked an inhibitory response in that MN, accompanied by a decrease of input resistance. These two effects were dramatically reduced in the presence of 5-HT. Thus 5-HT could be involved in mechanisms of dynamic reconfigurations of the neural network controlling leg movements in crayfish.

Naturally occurring compounds affect glutamatergic neurotransmission in rat brain.

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Martini, Lucia Helena; Jung, Fernanda; Soares, Felix Antunes; Rotta, Liane Nanci; Vendite, Deusa Aparecida; Frizzo, Marcos Emilio dos Santos; Yunes, Rosendo A; Calixto, João Batista; Wofchuk, Susana; Souza, Diogo O

2007-11-01

Natural products, including those derived from plants, have largely contributed to the development of therapeutic drugs. Glutamate is the main excitatory neurotransmitter in the central nervous system and it is also considered a nociceptive neurotransmitter, by acting on peripheral nervous system. For this reason, in this study we investigated the effects of the hydroalcoholic extracts from Drymis winteri (polygodial and drimanial), Phyllanthus (rutin and quercetine), Jathopha elliptica (jatrophone), Hedyosmum brasiliense (13HDS), Ocotea suaveolens (Tormentic acid), Protium kleinii (alphabeta-amyrin), Citrus paradise (naringin), soybean (genistein) and Crataeva nurvala (lupeol), described as having antinociceptive effects, on glutamatergic transmission parameters, such as [(3)H]glutamate binding, [(3)H]glutamate uptake by synaptic vesicles and astrocyte cultures, and synaptosomal [(3)H]glutamate release. All the glutamatergic parameters were affected by one or more of these compounds. Specifically, drimanial and polygodial presented more broad and profound effects, requiring more investigation on their mechanisms. The putative central side effects of these compounds, via the glutamatergic system, are discussed.

The balancing act of GABAergic synapse organizers.

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Ko, Jaewon; Choii, Gayoung; Um, Ji Won

2015-04-01

GABA (γ-aminobutyric acid) is the main neurotransmitter at inhibitory synapses in the mammalian brain. It is essential for maintaining the excitation and inhibition (E/I) ratio, whose imbalance underlies various brain diseases. Emerging information about inhibitory synapse organizers provides a novel molecular framework for understanding E/I balance at the synapse, circuit, and systems levels. This review highlights recent advances in deciphering these components of the inhibitory synapse and their roles in the development, transmission, and circuit properties of inhibitory synapses. We also discuss how their dysfunction may lead to a variety of brain disorders, suggesting new therapeutic strategies based on balancing the E/I ratio.

The influence of the glutamatergic system on cognition in schizophrenia: A systematic review.

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Thomas, Elizabeth H X; Bozaoglu, Kiymet; Rossell, Susan L; Gurvich, Caroline

2017-06-01

Previous literature showing the role of the glutamatergic system on cognition in schizophrenia has been inconclusive. 44 relevant pharmacological, candidate gene and neuroimaging studies were identified through systematic search following PRISMA guidelines. To be included, studies must have observed at least one objective measure of cognitive performance in patients with schizophrenia and either manipulated or measured the glutamatergic system. Of the cognitive domains observed, memory, working memory and executive functions appear to be most influenced by the glutamatergic pathway. In addition, evidence from the literature suggests that presynaptic components synthesis and uptake of glutamate is involved in memory, while postsynaptic signalling appears to be involved in working memory. In addition, it appears that the glutamatergic pathway is particularly involved in cognitive flexibility and learning potential in regards to executive functioning. The glutamatergic system appears to contribute to the cognitive deficits in schizophrenia, whereby different parts of the pathway are associated with different cognitive domains. This review demonstrates the necessity for cognition to be examined by domain as opposed to globally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developmental Connectivity and Molecular Phenotypes of Unique Cortical Projection Neurons that Express a Synapse-Associated Receptor Tyrosine Kinase.

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Kast, Ryan J; Wu, Hsiao-Huei; Levitt, Pat

2017-11-28

The complex circuitry and cell-type diversity of the cerebral cortex are required for its high-level functions. The mechanisms underlying the diversification of cortical neurons during prenatal development have received substantial attention, but understanding of neuronal heterogeneity is more limited during later periods of cortical circuit maturation. To address this knowledge gap, connectivity analysis and molecular phenotyping of cortical neuron subtypes that express the developing synapse-enriched MET receptor tyrosine kinase were performed. Experiments used a MetGFP transgenic mouse line, combined with coexpression analysis of class-specific molecular markers and retrograde connectivity mapping. The results reveal that MET is expressed by a minor subset of subcerebral and a larger number of intratelencephalic projection neurons. Remarkably, MET is excluded from most layer 6 corticothalamic neurons. These findings are particularly relevant for understanding the maturation of discrete cortical circuits, given converging evidence that MET influences dendritic elaboration and glutamatergic synapse maturation. The data suggest that classically defined cortical projection classes can be further subdivided based on molecular characteristics that likely influence synaptic maturation and circuit wiring. Additionally, given that MET is classified as a high confidence autism risk gene, the data suggest that projection neuron subpopulations may be differentially vulnerable to disorder-associated genetic variation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

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Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

2016-05-04

Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

Chronic stress from adolescence to aging in the prefrontal cortex: A neuroimmune perspective.

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Macht, Victoria A; Reagan, Lawrence P

2018-04-01

The development of the organism is a critical variable which influences the magnitude, duration, and reversibility of the effects of chronic stress. Such factors are relevant to the prefrontal cortex (PFC), as this brain region is the last to mature, the first to decline, and is highly stress-sensitive. Therefore, this review will examine the intersection between the nervous system and immune system at glutamatergic synapses in the PFC across three developmental periods: adolescence, adulthood, and aging. Glutamatergic synapses are tightly juxtaposed with microglia and astrocytes, and each of these cell types exhibits their own developmental trajectory. Not only does chronic stress differentially impact each of these cell types across development, but chronic stress also alters intercellular communication within this quad-partite synapse. These observations suggest that developmental shifts in both neural and immune function across neurons, microglia, and astrocytes mediate shifting effects of chronic stress on glutamatergic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.

A new measure for the strength of electrical synapses

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Julie S Haas

2015-09-01

Full Text Available Electrical synapses, like chemical synapses, mediate intraneuronal communication. Electrical synapses are typically quantified by subthreshold measurements of coupling, which fall short in describing their impact on spiking activity in coupled neighbors. Here we describe a novel measurement for electrical synapse strength that directly evaluates the effect of synaptically transmitted activity on spike timing. This method, also applicable to neurotransmitter-based synapses, communicates the considerable strength of electrical synapses. For electrical synapses measured in rodent slices of the thalamic reticular nucleus, spike timing is modulated by tens of ms by activity in a coupled neighbor.

Recombinant Bacillus thuringiensis subsp. kurstaki HD73 strain that synthesizes Cry1Ac and chimeric ChiA74∆sp chitinase inclusions.

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González-Ponce, Karen S; Casados-Vázquez, Luz E; Salcedo-Hernández, Rubén; Bideshi, Dennis K; Del Rincón-Castro, María C; Barboza-Corona, José E

2017-05-01

In this study, the endochitinase chiA74 gene lacking its secretion signal peptide sequence (chiA74∆sp) was fused in frame with the sequence coding for the C-terminal crystallization domain and transcription terminator of cry1Ac. The chimeric gene was expressed under the strong pcytA-p/STAB-SD promoter system in an acrystalliferous Cry - B strain of Bacillus thuringiensis and B. thuringiensis subsp. kurstaki HD73. We showed that the chimeric ChiA74∆sp produced amorphous inclusions in both Cry - B and HD73. In addition to the amorphous inclusions putatively composed of the chimera, bipyramidal Cry1Ac crystals, smaller than the wild-type crystal, were observed in recombinant HD73, and chitinase activity was remarkably higher (75-fold) in this strain when compared with parental HD73. Moreover, we observed that lyophilized samples of a mixture containing Cry1Ac, amorphous inclusions, and spores maintained chitinase activity. Amorphous inclusions could not be separated from Cry1Ac crystals by sucrose gradient centrifugation. Interestingly, the chitinase activity of purified Cry1Ac/amorphous inclusions was 51-fold higher compared to purified Cry1Ac inclusions of parental HD73, indicating that the increased enzymatic activity was due primarily to the presence of the atypical amorphous component. The possibility that the chimera is occluded with the Cry1Ac crystal, thereby contributing to the increased endochitinolytic activity, cannot be excluded. Finally, bioassays against larvae of Spodoptera frugiperda with spore/crystals of HD73 or spore-crystal ChiA74∆sp chimeric inclusions of recombinant HD73 strain showed LC 50 s of 396.86 and 290.25 ng/cm 2 , respectively. Our study suggests a possible practical application of the chimera in formulations of B. thuringiensis-based lepidopteran larvicides.

Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

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Facciolo Rosa

2011-01-01

Full Text Available Abstract Background Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB and hibernating (HIB hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR, 3-(+-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators. Results From the behavioral results it appears that the two glutamatergic compounds exerted distinct effects. In the first case local infusion of basolateral complexes (BLA with NMDAR antagonist caused very great (p Conclusion We conclude that predominant drinking events evoked by glutamatergic mechanisms, in the presence of prevalently down regulated levels of NR1/2A of some telencephalic and hypothalamic areas appear to constitute an important neuronal switch at least during arousal stage of hibernation. The establishment of the type of glutamatergic subtypes that are linked to successful hibernating states, via drinking stimuli, may have useful bearings toward sleeping disorders.

Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

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Heresco-Levy, Uriel

2003-10-01

The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

The study of ancient porcelain of Hutian kiln site from Five dynasty (902-979) to Ming dynasty (1368-1644) by INAA

International Nuclear Information System (INIS)

Lin Cheng; Junling Wang; Rongwu Li; Meitian Li

2015-01-01

Minor and trace elements of 398 pieces of ancient porcelain of Hutian kiln site from Five dynasty (AD 902-979) to Ming dynasty (AD 1368-1644) were determined by instrumental neutron activate analysis (INAA). The data of INAA and PCA show the ages of all the porcelain can be divided into Five dynasty, Northern Song dynasty, Southern Song dynasty, Early Yuan dynasty, Later Yuan dynasty and Ming dynasty according to their chemical compositions. Moreover, some archaeological questions about the ancient porcelain are discussion also. (author)

Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal.

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Sossin, Wayne S

2018-01-01

Synapses are diverse in form and function. While there are strong evidential and theoretical reasons for believing that memories are stored at synapses, the concept of a specialized "memory synapse" is rarely discussed. Here, we review the evidence that memories are stored at the synapse and consider the opposing possibilities. We argue that if memories are stored in an active fashion at synapses, then these memory synapses must have distinct molecular complexes that distinguish them from other synapses. In particular, examples from Aplysia sensory-motor neuron synapses and synapses on defined engram neurons in rodent models are discussed. Specific hypotheses for molecular complexes that define memory synapses are presented, including persistently active kinases, transmitter receptor complexes and trans-synaptic adhesion proteins.

Organizers of inhibitory synapses come of age.

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Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

2017-08-01

While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of Brain-Derived Neurotrophic Factor Exocytosis and Gamma-Aminobutyric Acidergic Interneuron Synapse by the Schizophrenia Susceptibility Gene Dysbindin-1.

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Yuan, Qiang; Yang, Feng; Xiao, Yixin; Tan, Shawn; Husain, Nilofer; Ren, Ming; Hu, Zhonghua; Martinowich, Keri; Ng, Julia S; Kim, Paul J; Han, Weiping; Nagata, Koh-Ichi; Weinberger, Daniel R; Je, H Shawn

2016-08-15

Genetic variations in dystrobrevin binding protein 1 (DTNBP1 or dysbindin-1) have been implicated as risk factors in the pathogenesis of schizophrenia. The encoded protein dysbindin-1 functions in the regulation of synaptic activity and synapse development. Intriguingly, a loss of function mutation in Dtnbp1 in mice disrupted both glutamatergic and gamma-aminobutyric acidergic transmission in the cerebral cortex; pyramidal neurons displayed enhanced excitability due to reductions in inhibitory synaptic inputs. However, the mechanism by which reduced dysbindin-1 activity causes inhibitory synaptic deficits remains unknown. We investigated the role of dysbindin-1 in the exocytosis of brain-derived neurotrophic factor (BDNF) from cortical excitatory neurons, organotypic brain slices, and acute slices from dysbindin-1 mutant mice and determined how this change in BDNF exocytosis transsynaptically affected the number of inhibitory synapses formed on excitatory neurons via whole-cell recordings, immunohistochemistry, and live-cell imaging using total internal reflection fluorescence microscopy. A decrease in dysbindin-1 reduces the exocytosis of BDNF from cortical excitatory neurons, and this reduction in BDNF exocytosis transsynaptically resulted in reduced inhibitory synapse numbers formed on excitatory neurons. Furthermore, application of exogenous BDNF rescued the inhibitory synaptic deficits caused by the reduced dysbindin-1 level in both cultured cortical neurons and slice cultures. Taken together, our results demonstrate that these two genes linked to risk for schizophrenia (BDNF and dysbindin-1) function together to regulate interneuron development and cortical network activity. This evidence supports the investigation of the association between dysbindin-1 and BDNF in humans with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effective Lactobacillus plantarum and Bifidobacterium infantis encapsulation with chia seed (Salvia hispanica L.) and flaxseed (Linum usitatissimum L.) mucilage and soluble protein by spray drying.

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Bustamante, Mariela; Oomah, B Dave; Rubilar, Mónica; Shene, Carolina

2017-02-01

Mucilage (M) and soluble protein (SP) extracted from chia seed and flaxseed were used as encapsulating material for two probiotic bacteria: Bifidobacterium infantis and Lactobacillus plantarum by spray drying. Probiotic survival and viability after spray drying and during storage were evaluated. B. infantis and L. plantarum displayed high survival (⩾98%) after encapsulation with mixtures of maltodextrin (MD) combined with M and SP from flaxseed (MD:FM:FSP - 7.5:0.2:7.5%, w/w/w) and chia seed (MD:CM:CSP - 7.5:0.6:7.5%, w/w/w), respectively. These ternary blends protected the probiotics and enhanced their resistance to simulated gastric juice and bile solution. Probiotics encapsulated with the ternary blends incorporated in instant juice powder exhibited high viability (>9Log10CFU/g) after 45days refrigerated storage. Encapsulation with the ternary blends reduced particle size of the probiotic powders thereby offering additional functional benefits. Our results reveal that chia seed and flaxseed are excellent sources of probiotic encapsulating agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stamatina Dimakopoulou onMing-QianMa’s Poetry as Re-Reading

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2010-05-01

Full Text Available Ming-Qian Ma. Poetry as Re-Reading: American Avant-Garde Poetry and the Poetics of Counter-Method. Evanston, Illinois: Northwestern University Press, 2008. Pp. 301. ISBN 978-0810124851In the Preface to the 1979 Enlarging the Temple: New Directions in American Poetry during the 1960s – Charles Altieri formulated a re-alignment that defined much criticism of postwar and contemporary American poetry to come. Altieri set “the work of Heidegger and the later Wittgenstein,” in resonance with the “i...

Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions

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Carmine Tomasetti

2017-01-01

Full Text Available Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of “synapse-based” psychiatric therapeutic strategies.

Synaptic glutamate release by postnatal rat serotonergic neurons in microculture.

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Johnson, M D

1994-02-01

Serotonergic neurons are thought to play a role in depression and obsessive compulsive disorder. However, their functional transmitter repertoire is incompletely known. To investigate this repertoire, intracellular recordings were obtained from 132 cytochemically identified rat mesopontine serotonergic neurons that had re-established synapses in microcultures. Approximately 60% of the neurons evoked excitatory glutamatergic potentials in themselves or in target neurons. Glutamatergic transmission was frequently observed in microcultures containing a solitary serotonergic neuron. Evidence for co-release of serotonin and glutamate from single raphe neurons was also obtained. However, evidence for gamma-aminobutyric acid release by serotonergic neurons was observed in only two cases. These findings indicate that many cultured serotonergic neurons form glutamatergic synapses and may explain several observations in slices and in vivo.

Ca(2+) influx and neurotransmitter release at ribbon synapses.

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Cho, Soyoun; von Gersdorff, Henrique

2012-01-01

Ca(2+) influx through voltage-gated Ca(2+) channels triggers the release of neurotransmitters at presynaptic terminals. Some sensory receptor cells in the peripheral auditory and visual systems have specialized synapses that express an electron-dense organelle called a synaptic ribbon. Like conventional synapses, ribbon synapses exhibit SNARE-mediated exocytosis, clathrin-mediated endocytosis, and short-term plasticity. However, unlike non-ribbon synapses, voltage-gated L-type Ca(2+) channel opening at ribbon synapses triggers a form of multiquantal release that can be highly synchronous. Furthermore, ribbon synapses appear to be specialized for fast and high throughput exocytosis controlled by graded membrane potential changes. Here we will discuss some of the basic aspects of synaptic transmission at different types of ribbon synapses, and we will emphasize recent evidence that auditory and retinal ribbon synapses have marked differences. This will lead us to suggest that ribbon synapses are specialized for particular operating ranges and frequencies of stimulation. We propose that different types of ribbon synapses transfer diverse rates of sensory information by expressing a particular repertoire of critical components, and by placing them at precise and strategic locations, so that a continuous supply of primed vesicles and Ca(2+) influx leads to fast, accurate, and ongoing exocytosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells

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Brill Monika S

2011-04-01

Full Text Available Abstract Background While the diversity and spatio-temporal origin of olfactory bulb (OB GABAergic interneurons has been studied in detail, much less is known about the subtypes of glutamatergic OB interneurons. Results We studied the temporal generation and diversity of Neurog2-positive precursor progeny using an inducible genetic fate mapping approach. We show that all subtypes of glutamatergic neurons derive from Neurog2 positive progenitors during development of the OB. Projection neurons, that is, mitral and tufted cells, are produced at early embryonic stages, while a heterogeneous population of glutamatergic juxtaglomerular neurons are generated at later embryonic as well as at perinatal stages. While most juxtaglomerular neurons express the T-Box protein Tbr2, those generated later also express Tbr1. Based on morphological features, these juxtaglomerular cells can be identified as tufted interneurons and short axon cells, respectively. Finally, targeted electroporation experiments provide evidence that while the majority of OB glutamatergic neurons are generated from intrabulbar progenitors, a small portion of them originate from extrabulbar regions at perinatal ages. Conclusions We provide the first comprehensive analysis of the temporal and spatial generation of OB glutamatergic neurons and identify distinct populations of juxtaglomerular interneurons that differ in their antigenic properties and time of origin.

Revisão: Composição química, propriedades funcionais e aplicações tecnológicas da semente de chia (Salvia hispanica L em alimentos

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Michele Silveira Coelho

2014-12-01

Full Text Available A chia (Salvia hispanica L. é uma semente antiga utilizada pelos maias e astecas como alimento para aumentar a resistência física. Essa semente é fonte natural de ácidos graxos ômega-3, fibras e proteínas, além de outros componentes nutricionais importantes, como os antioxidantes. Além disso, oferece um potencial na indústria de alimentos devido aos seus componentes funcionais, com aplicações no enriquecimento de pães, bolos e barras de cereais, produção de hidrolisados proteicos para aplicação em produtos de panificação, produção de maionese com adição de mucilagem de chia, entre outros produtos. Esta revisão tem como objetivo apresentar as possíveis aplicações em alimentos, demonstrando o quanto a chia ainda pode ser explorada nessa área.

Glutamatergic neurotransmission modulates hypoxia-induced hyperventilation but not anapyrexia

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Paula P.M. de

2004-01-01

Full Text Available The interaction between pulmonary ventilation (V E and body temperature (Tb is essential for O2 delivery to match metabolic rate under varying states of metabolic demand. Hypoxia causes hyperventilation and anapyrexia (a regulated drop in Tb, but the neurotransmitters responsible for this interaction are not well known. Since L-glutamate is released centrally in response to peripheral chemoreceptor stimulation and glutamatergic receptors are spread in the central nervous system we tested the hypothesis that central L-glutamate mediates the ventilatory and thermal responses to hypoxia. We measured V E and Tb in 40 adult male Wistar rats (270 to 300 g before and after intracerebroventricular injection of kynurenic acid (KYN, an ionotropic glutamatergic receptor antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG, a metabotropic glutamatergic receptor antagonist or vehicle (saline, followed by a 1-h period of hypoxia (7% inspired O2 or normoxia (humidified room air. Under normoxia, KYN (N = 5 or MCPG (N = 8 treatment did not affect V E or Tb compared to saline (N = 6. KYN and MCPG injection caused a decrease in hypoxia-induced hyperventilation (595 ± 49 for KYN, N = 7 and 525 ± 84 ml kg-1 min-1 for MCPG, N = 6; P < 0.05 but did not affect anapyrexia (35.3 ± 0.2 for KYN and 34.7 ± 0.4ºC for MCPG compared to saline (912 ± 110 ml kg-1 min-1 and 34.8 ± 0.2ºC, N = 8. We conclude that glutamatergic receptors are involved in hypoxic hyperventilation but do not affect anapyrexia, indicating that L-glutamate is not a common mediator of this interaction.

Exploring Triacylglycerol Biosynthetic Pathway in Developing Seeds of Chia (Salvia hispanica L.): A Transcriptomic Approach

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R. V., Sreedhar; Kumari, Priya; Rupwate, Sunny D.; Rajasekharan, Ram; Srinivasan, Malathi

2015-01-01

Chia (Salvia hispanica L.), a member of the mint family (Lamiaceae), is a rediscovered crop with great importance in health and nutrition and is also the highest known terrestrial plant source of heart-healthy omega-3 fatty acid, alpha linolenic acid (ALA). At present, there is no public genomic information or database available for this crop, hindering research on its genetic improvement through genomics-assisted breeding programs. The first comprehensive analysis of the global transcriptome...

Organization of central synapses by adhesion molecules.

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Tallafuss, Alexandra; Constable, John R L; Washbourne, Philip

2010-07-01

Synapses are the primary means for transmitting information from one neuron to the next. They are formed during the development of the nervous system, and the formation of appropriate synapses is crucial for the establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Organization of central synapses by adhesion molecules

OpenAIRE

Tallafuss, Alexandra; Constable, John R.L.; Washbourne, Philip

2010-01-01

Synapses are the primary means for transmitting information from one neuron to the next. They are formed during development of the nervous system, and formation of appropriate synapses is crucial for establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies ...

Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

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Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

2015-12-09

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are

FAT COMPOSITION AND FATTY ACID CHARACTERIZATION OF CHIA SEED (Salvia hispánica L.)

OpenAIRE

Mosquera Quelal, María; Reinoso García, María; Vásquez Castillo, Wilson

2017-01-01

The alterations of the lipid metabolism and the uncertainty at the moment of selecting beneficial foods to the human body lead to the investigation of omega fatty acids. The study is based on the evaluation of the effect of three preparation methods of chía seed, before getting the oil through two extraction methods and the characterization of the lipid fraction of chia seed (Salvia hispánica L.) from Colta-Ecuador. The oil yield of the conditioned seeds showed statistical differences. Regard...

Intercellular protein-protein interactions at synapses.

Science.gov (United States)

Yang, Xiaofei; Hou, Dongmei; Jiang, Wei; Zhang, Chen

2014-06-01

Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer's disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.

The Diversity of Cortical Inhibitory Synapses

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Yoshiyuki eKubota

2016-04-01

Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

Silent synapses in neuromuscular junction development.

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Tomàs, Josep; Santafé, Manel M; Lanuza, Maria A; García, Neus; Besalduch, Nuria; Tomàs, Marta

2011-01-01

In the last few years, evidence has been found to suggest that some synaptic contacts become silent but can be functionally recruited before they completely retract during postnatal synapse elimination in muscle. The physiological mechanism of developmental synapse elimination may be better understood by studying this synapse recruitment. This Mini-Review collects previously published data and new results to propose a molecular mechanism for axonal disconnection. The mechanism is based on protein kinase C (PKC)-dependent inhibition of acetylcholine (ACh) release. PKC activity may be stimulated by a methoctramine-sensitive M2-type muscarinic receptor and by calcium inflow though P/Q- and L-type voltage-dependent calcium channels. In addition, tropomyosin-related tyrosine kinase B (trkB) receptor-mediated brain-derived neurotrophic factor (BDNF) activity may oppose the PKC-mediated ACh release depression. Thus, a balance between trkB and muscarinic pathways may contribute to the final functional suppression of some neuromuscular synapses during development. © 2010 Wiley-Liss, Inc.

Comparative anatomy of phagocytic and immunological synapses

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Florence eNiedergang

2016-01-01

Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

Ketamine attenuates the glutamatergic neurotransmission in the ventral posteromedial nucleus slices of rats.

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Fu, Bao; Liu, Chengxi; Zhang, Yajun; Fu, Xiaoyun; Zhang, Lin; Yu, Tian

2017-08-23

Ketamine is a frequently used intravenous anesthetic, which can reversibly induce loss of consciousness (LOC). Previous studies have demonstrated that thalamocortical system is critical for information transmission and integration in the brain. The ventral posteromedial nucleus (VPM) is a critical component of thalamocortical system. Glutamate is an important excitatory neurotransmitter in the brain and may be involved in ketamine-induced LOC. The study used whole-cell patch-clamp to observe the effect of ketamine (30 μM-1000 μM) on glutamatergic neurotransmission in VPM slices. Ketamine significantly decreased the amplitude of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs), but only higher concentration of ketamine (300 μM and 1000 μM) suppressed the frequency of sEPSCs. Ketamine (100 μM-1000 μM) also decreased the amplitude of glutamatergic miniature excitatory postsynaptic currents (mEPSCs), without altering the frequency. In VPM neurons, ketamine attenuates the glutamatergic neurotransmission mainly through postsynaptic mechanism and action potential may be involved in the process.

Energy-efficient neuron, synapse and STDP integrated circuits.

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Cruz-Albrecht, Jose M; Yung, Michael W; Srinivasa, Narayan

2012-06-01

Ultra-low energy biologically-inspired neuron and synapse integrated circuits are presented. The synapse includes a spike timing dependent plasticity (STDP) learning rule circuit. These circuits have been designed, fabricated and tested using a 90 nm CMOS process. Experimental measurements demonstrate proper operation. The neuron and the synapse with STDP circuits have an energy consumption of around 0.4 pJ per spike and synaptic operation respectively.

Synapse Pathology in Psychiatric and Neurologic Disease

NARCIS (Netherlands)

M. van Spronsen (Myrrhe); C.C. Hoogenraad (Casper)

2010-01-01

textabstractInhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical

Liraglutide Modulates Appetite and Body Weight Via GLP-1R-Expressing Glutamatergic Neurons.

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Adams, Jessica M; Pei, Hongjuan; Sandoval, Darleen A; Seeley, Randy J; Chang, Rui B; Liberles, Stephen D; Olson, David P

2018-05-18

Glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) impact appetite and body weight are still not fully understood. Here, we determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the acute and chronic effects of the GLP1RA liraglutide on food intake, visceral illness, body weight and neural network activation. We found that mice lacking GLP-1Rs in vGAT -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2 -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding. Concomitantly, deletion of GLP-1Rs from glutamatergic neurons completely abolished the neural network activation observed after liraglutide administration. We conclude that liraglutide activates a dispersed but discrete neural network to mediate its physiological effects, and that these effects require GLP-1R expression on glutamatergic but not GABAergic neurons. © 2018 by the American Diabetes Association.

‘Unable to think in my mother’s tongue’: immigrant daughters in Alice Pung’s 'Unpolished Gem' and Hsu-Ming Teo’s 'Behind the Moon'

OpenAIRE

Alice Healy

2010-01-01

This paper explores ‘the immigrant’s story in translation’ through the various instances of language spoken between parents and children. It analyses the experience of immigrant daughters in two ‘Asian-Australian’ texts – Alice Pung’s recent memoir Unpolished Gem and Hsu-Ming Teo’s Behind the Moon. I position these texts in the context of the reception of literature labelled ‘Asian-Australian’ in the market, exploring Hsu-Ming Teo’s critique of such positioning. Centrally, the paper examine...

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

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Chung, Won-Suk; Clarke, Laura E.; Wang, Gordon X.; Stafford, Benjamin K.; Sher, Alexander; Chakraborty, Chandrani; Joung, Julia; Foo, Lynette C.; Thompson, Andrew; Chen, Chinfei; Smith, Stephen J.; Barres, Ben A.

2013-12-01

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.

Functional bread with n-3 alpha linolenic acid from whole chia (Salvia hispanica L.) flour

OpenAIRE

Luna Pizarro, Patricia; Almeida, Eveline Lopes; Coelho, Alessandra Silva; Sammán, Norma Cristina; Hubinger, Miriam Dupas; Chang, Yoon Kil

2014-01-01

This work proposed to study the effects of the addition of whole chia flour (WCF) on the technological, nutritional and sensory qualities of bread. Different WCF contents (0 and 20 %) and vital gluten (VG) (0 and 4 %) were added to bread according to a 22 central composite rotational design. WCF decreased the specific volume, lightness and hue angle of the bread loaves, but did not affect the chroma values. WCF and VG contributed to maintenance of the moisture content of the loaves during the...

Evidence for presynaptically silent synapses in the immature hippocampus

International Nuclear Information System (INIS)

Yoon, Jae Young; Choi, Sukwoo

2017-01-01

Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses. Glutamate transients predicted based on the two presynaptic mechanisms have been shown to activate only high-affinity NMDARs, but not low-affinity AMPARs. Interestingly, a previous study has developed a new approach to distinguish between the two presynaptic mechanisms using dextran, an inert macromolecule that reduces the diffusivity of released glutamate: postsynaptic responses through the fusion pore mechanism, but not through the spillover mechanism, are potentiated by reduced glutamate diffusivity. Therefore, we reasoned that if the fusion pore mechanism underlies silent synapses, dextran application would reveal AMPAR-mediated synaptic responses at silent synapses. In the present study, we recorded AMPAR-mediated synaptic responses at the CA3-CA1 synapses in neonatal rats in the presence of blockers for NMDARs and GABAARs. Bath application of dextran revealed synaptic responses at silent synapses. GYKI53655, a selective AMPAR-antagonist, completely inhibited the unsilenced synaptic responses, indicating that the unsilenced synaptic responses are mediated by AMPARs. The dextran-mediated reduction in glutamate diffusivity would also lead to the activation of metabotropic glutamate receptors (mGluRs), which might induce unsilencing via the activation of unknown intracellular signaling. Hence, we determined whether mGluR-blockers alter

The biochemical anatomy of cortical inhibitory synapses.

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Elizabeth A Heller

Full Text Available Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from the cerebral cortex. We show that these synaptic complexes contain a variety of neurotransmitter receptors, neural cell-scaffolding and adhesion molecules, but that they are entirely lacking in cell signaling proteins. This fundamental distinction between the functions of type 1 and type 2 synapses in the nervous system has far reaching implications for models of synaptic plasticity, rapid adaptations in neural circuits, and homeostatic mechanisms controlling the balance of excitation and inhibition in the mature brain.

[Some problems concerning the population thought in the Ming and Quing dynasties].

Science.gov (United States)

Zhang, M R

1982-09-29

After the middle of the Ming dynasty, the Chinese feudal system began to show some influence of capitalism in its production models. Changes began to take place in its political and economic systems. In 1723, a new method of household taxation was adopted to replace the traditional taxation system, which had been based upon the population of each household. Under the new system, taxation was based upon the size of the land each household owned. As a result of this change, the population showed rapid growth. Intellectuals began to form the concept of curbing excessive population growth. They also began to pay attention to the problems of adequate material supplies, overpopulation, and possible solutions. Chinese intellectuals and scholars of the late Ming and Qing dynasties, including Xu Guangqi, Hong Liangji, Wang Shifeng, and Xue Fucheng realized the serious nature of population growth. In fact, the population figure doubledever 30 years on a regular basis. The rapid population growth caused a decline in the living standard, higher prices for consumer goods, unemployment, a decline in the population quality, and social disorders. Hong Liangji suggested that natural disasters such as floods and droughts could help reduce the population, and that improvement in agriculture, emigration, and tax reductions could promote production. Wang Shifeng was in favor of using severe laws and restrictions on marriage to control population. Xue Fucheng proposed the idea of imitating Western countries to develop capitalism and industries and increase employment opportunities to reduce the pressure of the rapid population growth.

Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

Science.gov (United States)

Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

2016-01-01

Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Low voltage-activated calcium channels gate transmitter release at the dorsal root ganglion sandwich synapse.

Science.gov (United States)

Rozanski, Gabriela M; Nath, Arup R; Adams, Michael E; Stanley, Elise F

2013-11-15

A subpopulation of dorsal root ganglion (DRG) neurons are intimately attached in pairs and separated solely by thin satellite glial cell membrane septa. Stimulation of one neuron leads to transglial activation of its pair by a bi-, purinergic/glutamatergic synaptic pathway, a transmission mechanism that we term sandwich synapse (SS) transmission. Release of ATP from the stimulated neuron can be attributed to a classical mechanism involving Ca(2+) entry via voltage-gated calcium channels (CaV) but via an unknown channel type. Specific blockers and toxins ruled out CaV1, 2.1 and 2.2. Transmission was, however, blocked by a moderate depolarization (-50 mV) or low-concentration Ni(2+) (0.1 mM). Transmission persisted using a voltage pulse to -40 mV from a holding potential of -80 mV, confirming the involvement of a low voltage-activated channel type and limiting the candidate channel type to either CaV3.2 or a subpopulation of inactivation- and Ni(2+)-sensitive CaV2.3 channels. Resistance of the neuron calcium current and SS transmission to SNX482 argue against the latter. Hence, we conclude that inter-somatic transmission at the DRG SS is gated by CaV3.2 type calcium channels. The use of CaV3 family channels to gate transmission has important implications for the biological function of the DRG SS as information transfer would be predicted to occur not only in response to action potentials but also to sub-threshold membrane voltage oscillations. Thus, the SS synapse may serve as a homeostatic signalling mechanism between select neurons in the DRG and could play a role in abnormal sensation such as neuropathic pain.

Short-term ionic plasticity at GABAergic synapses

Directory of Open Access Journals (Sweden)

Joseph Valentino Raimondo

2012-10-01

Full Text Available Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the postsynaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell’s ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.

mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.

Directory of Open Access Journals (Sweden)

Chris P Jew

Full Text Available The group I metabotropic glutamate receptor 5 (mGluR5 has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.

How synapses can enhance sensibility of a neural network

Science.gov (United States)

Protachevicz, P. R.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Baptista, M. S.; Viana, R. L.; Lameu, E. L.; Macau, E. E. N.; Batista, A. M.

2018-02-01

In this work, we study the dynamic range in a neural network modelled by cellular automaton. We consider deterministic and non-deterministic rules to simulate electrical and chemical synapses. Chemical synapses have an intrinsic time-delay and are susceptible to parameter variations guided by learning Hebbian rules of behaviour. The learning rules are related to neuroplasticity that describes change to the neural connections in the brain. Our results show that chemical synapses can abruptly enhance sensibility of the neural network, a manifestation that can become even more predominant if learning rules of evolution are applied to the chemical synapses.

Communication Breakdown: The Impact of Ageing on Synapse Structure

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Petralia, Ronald S.; Mattson, Mark P.; Yao, Pamela J.

2014-01-01

Impaired synaptic plasticity is implicated in the functional decline of the nervous system associated with ageing. Understanding the structure of ageing synapses is essential to understanding the functions of these synapses and their role in the ageing nervous system. In this review, we summarize studies on ageing synapses in vertebrates and invertebrates, focusing on changes in morphology and ultrastructure. We cover different parts of the nervous system, including the brain, the retina, the cochlea, and the neuromuscular junction. The morphological characteristics of aged synapses could shed light on the underlying molecular changes and their functional consequences. PMID:24495392

Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect.

Science.gov (United States)

Yuan, Kejing; Sheng, Huan; Song, Jiaojiao; Yang, Li; Cui, Dongyang; Ma, Qianqian; Zhang, Wen; Lai, Bin; Chen, Ming; Zheng, Ping

2017-11-01

Drug addiction is a chronic brain disorder characterized by the compulsive repeated use of drugs. The reinforcing effect of repeated use of drugs on reward plays an important role in morphine-induced addictive behaviors. The nucleus accumbens (NAc) is an important site where morphine treatment produces its reinforcing effect on reward. However, how morphine treatment produces its reinforcing effect on reward in the NAc remains to be clarified. In the present study, we studied the influence of morphine treatment on the effects of DA and observed whether morphine treatment could directly change glutamatergic synaptic transmission in the NAc. We also explored the functional significance of morphine-induced potentiation of glutamatergic synaptic transmission in the NAc at behavioral level. Our results show that (1) morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc neurons; (2) morphine treatment potentiates glutamatergic input onto NAc neurons, especially the one from the basolateral amygdala (BLA) to the NAc; (3) blockade of glutamatergic synaptic transmission in the NAc or ablation of projection neurons from BLA to NAc significantly decreases morphine treatment-induced increase in locomotor activity. These results suggest that morphine treatment enhances glutamatergic input onto neurons of the NAc via both disinhibitory and stimulating effect and therefore increases locomotor activity. © 2016 Society for the Study of Addiction.

Properties, characterization, and decay of sticky rice–lime mortars from the Wugang Ming dynasty city wall (China)

Energy Technology Data Exchange (ETDEWEB)

Xiao, Ya [State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083 (China); Cultural Relics and Archaeology Institute of Hunan, Changsha 410083 (China); Fu, Xuan; Gu, Haibing [Cultural Relics and Archaeology Institute of Hunan, Changsha 410083 (China); Gao, Feng [State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083 (China); Liu, Shaojun, E-mail: liumatthew@csu.edu.cn [State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083 (China)

2014-04-01

Urgent restoration of the Wugang Ming dynasty city wall brings about the need for a study of the formulation and properties of mortars. In the present paper, mortar samples from the Wugang Ming dynasty city wall were characterized in a combination of sheet polarized light optical microscopy, scanning electron microscopy with X-ray energy dispersive spectrometer, thermogravimetric/differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and inductively coupled plasma emission spectroscopy. Results show that mortars are mainly built up from inorganic calcium carbonate based organic–inorganic hybrid material with a small amount of sticky rice, which plays a crucial role in forming dense and compact microstructure of mortars and effectively hindering penetration of water and air into mortars. Analysis of decayed products shows that the detrimental soluble salts originates from ambient environment. - Highlights: • Mortars used in the Wugang city wall are a calcium carbonate-sticky rice hybrid bonding material. • Carbonation processing is extremely slow due to dense and compact microstructure of mortars. • Decying of mortars results from the appearance of soluble salt from ambient environment.

Properties, characterization, and decay of sticky rice–lime mortars from the Wugang Ming dynasty city wall (China)

International Nuclear Information System (INIS)

Xiao, Ya; Fu, Xuan; Gu, Haibing; Gao, Feng; Liu, Shaojun

2014-01-01

Urgent restoration of the Wugang Ming dynasty city wall brings about the need for a study of the formulation and properties of mortars. In the present paper, mortar samples from the Wugang Ming dynasty city wall were characterized in a combination of sheet polarized light optical microscopy, scanning electron microscopy with X-ray energy dispersive spectrometer, thermogravimetric/differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and inductively coupled plasma emission spectroscopy. Results show that mortars are mainly built up from inorganic calcium carbonate based organic–inorganic hybrid material with a small amount of sticky rice, which plays a crucial role in forming dense and compact microstructure of mortars and effectively hindering penetration of water and air into mortars. Analysis of decayed products shows that the detrimental soluble salts originates from ambient environment. - Highlights: • Mortars used in the Wugang city wall are a calcium carbonate-sticky rice hybrid bonding material. • Carbonation processing is extremely slow due to dense and compact microstructure of mortars. • Decying of mortars results from the appearance of soluble salt from ambient environment

Neural Activity During The Formation Of A Giant Auditory Synapse

NARCIS (Netherlands)

M.C. Sierksma (Martijn)

2018-01-01

markdownabstractThe formation of synapses is a critical step in the development of the brain. During this developmental stage neural activity propagates across the brain from synapse to synapse. This activity is thought to instruct the precise, topological connectivity found in the sensory central

Presynaptic proteoglycans: sweet organizers of synapse development.

Science.gov (United States)

Song, Yoo Sung; Kim, Eunjoon

2013-08-21

Synaptic adhesion molecules control neuronal synapse development. In this issue of Neuron, Siddiqui et al. (2013) and de Wit et al. (2013) demonstrate that LRRTM4, a postsynaptic adhesion molecule, trans-synaptically interacts with presynaptic heparan sulfate proteoglycans (HSPGs) to promote synapse development. Copyright © 2013 Elsevier Inc. All rights reserved.

Interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in minimal hepatic encephalopathy.

Science.gov (United States)

Llansola, Marta; Montoliu, Carmina; Agusti, Ana; Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Gomez-Gimenez, Belen; Malaguarnera, Michele; Dadsetan, Sherry; Belghiti, Majedeline; Garcia-Garcia, Raquel; Balzano, Tiziano; Taoro, Lucas; Felipo, Vicente

2015-09-01

The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in different brain areas and neuronal circuits. There is an interplay between glutamatergic and GABAergic neurotransmission alterations in cognitive and motor impairment in HE. This interplay may occur: (a) in different brain areas involved in specific neuronal circuits; (b) in the same brain area through cross-modulation of glutamatergic and GABAergic neurotransmission. We will summarize some examples of the (1) interplay between glutamatergic and GABAergic neurotransmission alterations in different areas in the basal ganglia-thalamus-cortex circuit in the motor alterations in minimal hepatic encephalopathy (MHE); (2) interplay between glutamatergic and GABAergic neurotransmission alterations in cerebellum in the impairment of cognitive function in MHE through altered function of the glutamate-nitric oxide-cGMP pathway. We will also comment the therapeutic implications of the above studies and the utility of modulators of glutamate and GABA receptors to restore cognitive and motor function in rats with hyperammonemia and hepatic encephalopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Calcium channel-dependent molecular maturation of photoreceptor synapses.

Directory of Open Access Journals (Sweden)

Nawal Zabouri

Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

Calcium channel-dependent molecular maturation of photoreceptor synapses.

Science.gov (United States)

Zabouri, Nawal; Haverkamp, Silke

2013-01-01

Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V)1.4(α(1F)) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V)1.4(α(1F)) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V)1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V)1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V)1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

Microbial Impacts to the Near-Field Environment Geochemistry (MING): A Model for Estimating Microbial Communities in Repository Drifts at Yucca Mountain

International Nuclear Information System (INIS)

Jolley, D.M.; Ehrhorn, T.F.; Horn, J.

2002-01-01

Geochemical and microbiological modeling was performed to evaluate the potential quantities and impact of microorganisms on the geochemistry of the area adjacent to and within nuclear waste packages in the proposed repository drifts at Yucca Mountain, Nevada. The microbial growth results from the introduction of water, ground support, and waste package materials into the deep unsaturated rock. The simulations, which spanned one million years, were accomplished using a newly developed computer code, Microbial Impacts to the Near-Field Environment Geochemistry (MING). MING uses environmental thresholds for limiting microbial growth to temperatures below 120 C and above relative humidities of 90 percent in repository drifts. Once these thresholds are met, MING expands upon a mass balance and thermodynamic approach proposed by McKinley and others (1997), by using kinetic rates to supply constituents from design materials and constituent fluxes including solubilized rock components into the drift, to perform two separate mass-balance calculations as a function of time. The first (nutrient limit) assesses the available nutrients (C, N, P and S) and calculates how many microorganisms can be produced based on a microorganism stoichiometry of C 160 (H 280 O 80 )N 30 P 2 S. The second (energy limit) calculates the energy available from optimally combined redox couples for the temperature, and pH at that time. This optimization maximizes those reactions that produce > 15kJ/mol (limit on useable energy) using an iterative linear optimization technique. The final available energy value is converted to microbial mass at a rate of 1 kg of biomass (dry weight) for every 64 MJ of energy. These two values (nutrient limit and energy limit) are then compared and the smaller value represents the number of microorganisms that can be produced over a specified time. MING can also be adapted to investigate other problems of interest as the model can be used in saturated and unsaturated

IR wireless cluster synapses of HYDRA very large neural networks

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Jannson, Tomasz; Forrester, Thomas

2008-04-01

RF/IR wireless (virtual) synapses are critical components of HYDRA (Hyper-Distributed Robotic Autonomy) neural networks, already discussed in two earlier papers. The HYDRA network has the potential to be very large, up to 10 11-neurons and 10 18-synapses, based on already established technologies (cellular RF telephony and IR-wireless LANs). It is organized into almost fully connected IR-wireless clusters. The HYDRA neurons and synapses are very flexible, simple, and low-cost. They can be modified into a broad variety of biologically-inspired brain-like computing capabilities. In this third paper, we focus on neural hardware in general, and on IR-wireless synapses in particular. Such synapses, based on LED/LD-connections, dominate the HYDRA neural cluster.

Rhythmic changes in synapse numbers in Drosophila melanogaster motor terminals.

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Santiago Ruiz

Full Text Available Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD cycles and constant darkness (DD. We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.

Cell adhesion and matricellular support by astrocytes of the tripartite synapse

NARCIS (Netherlands)

Hillen, Anne E J; Burbach, J Peter H; Hol, Elly M

2018-01-01

Astrocytes contribute to the formation, function, and plasticity of synapses. Their processes enwrap the neuronal components of the tripartite synapse, and due to this close interaction they are perfectly positioned to modulate neuronal communication. The interaction between astrocytes and synapses

Cell Biology of Astrocyte-Synapse Interactions.

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Allen, Nicola J; Eroglu, Cagla

2017-11-01

Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development. Copyright © 2017 Elsevier Inc. All rights reserved.

Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

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Wolf, G; Schmidt, W

1983-01-01

A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

Defects of the Glycinergic Synapse in Zebrafish

Science.gov (United States)

Ogino, Kazutoyo; Hirata, Hiromi

2016-01-01

Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nociceptive processing. The importance of the glycinergic synapse is conserved across vertebrate species. A teleost fish, the zebrafish, offers several advantages as a vertebrate model for research of glycinergic synapse. Mutagenesis screens in zebrafish have isolated two motor defective mutants that have pathogenic mutations in glycinergic synaptic transmission: bandoneon (beo) and shocked (sho). Beo mutants have a loss-of-function mutation of glycine receptor (GlyR) β-subunit b, alternatively, sho mutant is a glycinergic transporter 1 (GlyT1) defective mutant. These mutants are useful animal models for understanding of glycinergic synaptic transmission and for identification of novel therapeutic agents for human diseases arising from defect in glycinergic transmission, such as hyperekplexia or glycine encephalopathy. Recent advances in techniques for genome editing and for imaging and manipulating of a molecule or a physiological process make zebrafish more attractive model. In this review, we describe the glycinergic defective zebrafish mutants and the technical advances in both forward and reverse genetic approaches as well as in vivo visualization and manipulation approaches for the study of the glycinergic synapse in zebrafish. PMID:27445686

Communication, the centrosome and the immunological synapse.

Science.gov (United States)

Stinchcombe, Jane C; Griffiths, Gillian M

2014-09-05

Recent findings on the behaviour of the centrosome at the immunological synapse suggest a critical role for centrosome polarization in controlling the communication between immune cells required to generate an effective immune response. The features observed at the immunological synapse show parallels to centrosome (basal body) polarization seen in cilia and flagella, and the cellular communication that is now known to occur at all of these sites.

Stochastic resonance in small-world neuronal networks with hybrid electrical–chemical synapses

International Nuclear Information System (INIS)

Wang, Jiang; Guo, Xinmeng; Yu, Haitao; Liu, Chen; Deng, Bin; Wei, Xile; Chen, Yingyuan

2014-01-01

Highlights: •We study stochastic resonance in small-world neural networks with hybrid synapses. •The resonance effect depends largely on the probability of chemical synapse. •An optimal chemical synapse probability exists to evoke network resonance. •Network topology affects the stochastic resonance in hybrid neuronal networks. - Abstract: The dependence of stochastic resonance in small-world neuronal networks with hybrid electrical–chemical synapses on the probability of chemical synapse and the rewiring probability is investigated. A subthreshold periodic signal is imposed on one single neuron within the neuronal network as a pacemaker. It is shown that, irrespective of the probability of chemical synapse, there exists a moderate intensity of external noise optimizing the response of neuronal networks to the pacemaker. Moreover, the effect of pacemaker driven stochastic resonance of the system depends largely on the probability of chemical synapse. A high probability of chemical synapse will need lower noise intensity to evoke the phenomenon of stochastic resonance in the networked neuronal systems. In addition, for fixed noise intensity, there is an optimal chemical synapse probability, which can promote the propagation of the localized subthreshold pacemaker across neural networks. And the optimal chemical synapses probability turns even larger as the coupling strength decreases. Furthermore, the small-world topology has a significant impact on the stochastic resonance in hybrid neuronal networks. It is found that increasing the rewiring probability can always enhance the stochastic resonance until it approaches the random network limit

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

Science.gov (United States)

Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG

An Exploratory Study of Spectroscopic Glutamatergic Correlates of Cortical Excitability in Depressed Adolescents

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Charles P. Lewis

2016-11-01

Full Text Available Introduction: Transcranial magnetic stimulation (TMS research has suggested dysfunction in cortical glutamatergic systems in depression, while proton magnetic resonance spectroscopy (1H-MRS studies have demonstrated deficits in concentrations of glutamatergic metabolites in depressed individuals in several cortical regions, including the anterior cingulate cortex (ACC. However, few studies have combined TMS and MRS methods to examine relationships between glutamatergic neurochemistry and excitatory and inhibitory neural functions, and none have utilized TMS-MRS methodology in clinical populations or in youth. This exploratory study aimed to examine relationships between TMS measures of cortical excitability and inhibition and concentrations of glutamatergic metabolites as measured by 1H-MRS in depressed adolescents. Methods: Twenty-four children and adolescents (aged 11-18 years with depressive symptoms underwent TMS testing, which included measures of the resting motor threshold (RMT, cortical silent period (CSP, short-interval intracortical inhibition (SICI, and intracortical facilitation (ICF. Fourteen participants from the same sample also completed 1H-MRS in a 3 T MRI scanner after TMS testing. Glutamate + glutamine (Glx concentrations were measured in medial ACC and left primary motor cortex voxels with a TE-optimized PRESS sequence. Metabolite concentrations were corrected for cerebrospinal fluid after tissue segmentation. Pearson product-moment and Spearman rank-order correlations were calculated to assess relationships between TMS measures and Glx. Results: In the left primary motor cortex voxel, Glx had a significant positive correlation with the RMT. In the medial ACC voxel, Glx had significant positive correlations with ICF at the 10-ms and 20-ms ISIs.Conclusions: These preliminary data implicate glutamate in cortical excitatory processes measured by TMS. Limitations included small sample size, lack of healthy control comparators

Recruitment of activation receptors at inhibitory NK cell immune synapses.

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Nicolas Schleinitz

2008-09-01

Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

A shared synapse architecture for efficient FPGA implementation of autoencoders.

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Suzuki, Akihiro; Morie, Takashi; Tamukoh, Hakaru

2018-01-01

This paper proposes a shared synapse architecture for autoencoders (AEs), and implements an AE with the proposed architecture as a digital circuit on a field-programmable gate array (FPGA). In the proposed architecture, the values of the synapse weights are shared between the synapses of an input and a hidden layer, and between the synapses of a hidden and an output layer. This architecture utilizes less of the limited resources of an FPGA than an architecture which does not share the synapse weights, and reduces the amount of synapse modules used by half. For the proposed circuit to be implemented into various types of AEs, it utilizes three kinds of parameters; one to change the number of layers' units, one to change the bit width of an internal value, and a learning rate. By altering a network configuration using these parameters, the proposed architecture can be used to construct a stacked AE. The proposed circuits are logically synthesized, and the number of their resources is determined. Our experimental results show that single and stacked AE circuits utilizing the proposed shared synapse architecture operate as regular AEs and as regular stacked AEs. The scalability of the proposed circuit and the relationship between the bit widths and the learning results are also determined. The clock cycles of the proposed circuits are formulated, and this formula is used to estimate the theoretical performance of the circuit when the circuit is used to construct arbitrary networks.

Pedestrian Dharma: Slowness and Seeing in Tsai Ming-Liang’s Walker

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Teng-Kuan Ng

2018-06-01

Full Text Available This paper studies the ways that Walker, a short film by the Malaysian-Taiwanese auteur Tsai Ming-Liang, visualizes the relationship between Buddhism and modernity. Via detailed film analysis as well as attention to sources in premodern Buddhist traditions, this paper argues that its filmic performance of Zen walking meditation serves two functions: To present slowness and simplicity as prophetic counterpoints against the dizzying excesses of the contemporary metropolis; and to offer contemplative attentiveness as a therapeutic resource for life in the modern world. By instantiating and cultivating critical shifts in viewerly perspective in the manner of Buddhist ritual practice, Walker invites us to envision how a place of frenetic distraction or pedestrian mundaneness might be transfigured into a site of beauty, wonder, and liberation.

Microbial Impacts to the Near-Field Environment Geochemistry (MING): A Model for Estimating Microbial Communities in Repository Drifts at Yucca Mountain

Energy Technology Data Exchange (ETDEWEB)

D.M. Jolley; T.F. Ehrhorn; J. Horn

2002-03-19

Geochemical and microbiological modeling was performed to evaluate the potential quantities and impact of microorganisms on the geochemistry of the area adjacent to and within nuclear waste packages in the proposed repository drifts at Yucca Mountain, Nevada. The microbial growth results from the introduction of water, ground support, and waste package materials into the deep unsaturated rock. The simulations, which spanned one million years, were accomplished using a newly developed computer code, Microbial Impacts to the Near-Field Environment Geochemistry (MING). MING uses environmental thresholds for limiting microbial growth to temperatures below 120 C and above relative humidities of 90 percent in repository drifts. Once these thresholds are met, MING expands upon a mass balance and thermodynamic approach proposed by McKinley and others (1997), by using kinetic rates to supply constituents from design materials and constituent fluxes including solubilized rock components into the drift, to perform two separate mass-balance calculations as a function of time. The first (nutrient limit) assesses the available nutrients (C, N, P and S) and calculates how many microorganisms can be produced based on a microorganism stoichiometry of C{sub 160}(H{sub 280}O{sub 80})N{sub 30}P{sub 2}S. The second (energy limit) calculates the energy available from optimally combined redox couples for the temperature, and pH at that time. This optimization maximizes those reactions that produce > 15kJ/mol (limit on useable energy) using an iterative linear optimization technique. The final available energy value is converted to microbial mass at a rate of 1 kg of biomass (dry weight) for every 64 MJ of energy. These two values (nutrient limit and energy limit) are then compared and the smaller value represents the number of microorganisms that can be produced over a specified time. MING can also be adapted to investigate other problems of interest as the model can be used in saturated

The cytotoxic T lymphocyte immune synapse at a glance.

Science.gov (United States)

Dieckmann, Nele M G; Frazer, Gordon L; Asano, Yukako; Stinchcombe, Jane C; Griffiths, Gillian M

2016-08-01

The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers. © 2016. Published by The Company of Biologists Ltd.

White-and-blud porcelain of Hutian kiln in Ming dynasty studied by PIXE

International Nuclear Information System (INIS)

Cheng Lin; Feng Songlin; Sha Yin; Cheng Huansheng

2004-01-01

The study of provenance, ages and distinguishing precious ancient porcelain from a fake of Chinese ancient porcelain by modern technologies arose greatly interesting in the circles of archaeologists and scientists in China. Concentration of major and trace elements of white-and-blue porcelain of Hutian kiln in Ming Dynasty were analyzed by PIXE, and elemental distributions of porcelain were analyzed by SPM. The results indicate the elemental distributions in the white glaze, blue glaze and body are homogeneous, respectively. It is a layer nearly 5-10 μm between the body and blue glaze. Probably, cobalt blue pigment used in the blue glaze comes from Jiangxi, Fujian province etc. (authors)

Defects of the Glycinergic Synapse in Zebrafish

OpenAIRE

Ogino, Kazutoyo; Hirata, Hiromi

2016-01-01

Glycine mediates fast inhibitory synaptic transmission. Physiological importance of the glycinergic synapse is well established in the brainstem and the spinal cord. In humans, the loss of glycinergic function in the spinal cord and brainstem leads to hyperekplexia, which is characterized by an excess startle reflex to sudden acoustic or tactile stimulation. In addition, glycinergic synapses in this region are also involved in the regulation of respiration and locomotion, and in the nocicepti...

NKp46 clusters at the immune synapse and regulates NK cell polarization

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Uzi eHadad

2015-09-01

Full Text Available Natural killer cells play an important role in first-line defense against tumor and virus-infected cells. The activity of NK cells is tightly regulated by a repertoire of cell-surface expressed inhibitory and activating receptors. NKp46 is a major NK cell activating receptor that is involved in the elimination of target cells. NK cells form different types of synapses that result in distinct functional outcomes: cytotoxic, inhibitory, and regulatory. Recent studies revealed that complex integration of NK receptor signaling controls cytoskeletal rearrangement and other immune synapse-related events. However the distinct nature by which NKp46 participates in NK immunological synapse formation and function remains unknown. In this study we determined that NKp46 forms microclusters structures at the immune synapse between NK cells and target cells. Over-expression of human NKp46 is correlated with increased accumulation of F-actin mesh at the immune synapse. Concordantly, knock-down of NKp46 in primary human NK cells decreased recruitment of F-actin to the synapse. Live cell imaging experiments showed a linear correlation between NKp46 expression and lytic granules polarization to the immune synapse. Taken together, our data suggest that NKp46 signaling directly regulates the NK lytic immune synapse from early formation to late function.

[Exploration on an overview of history (from Chunqiu to Ming and Qing Dynasties) and species of Chinese exotic traditional medicine].

Science.gov (United States)

Jia, Min-Ru; Wang, Tian-Tian; Lu, Xiao-Lin; Ma, Yu-Ying

2017-05-01

This paper collected and analyzed literatures about starting of traditional medicine and trading of different medicine from Chunqiu Zhanguo to Ming and Qing Dynasties, in order to preliminarily explore on an overview of specie of chinese exotic traditional medicine and trade of different country in different dynasty（from Chunqiu to Ming and Qing Dynasties）, as well as the amount of exotic medicine over two thousand years. (remove repeating and doubtful species), find peculiarity of exotic medicine, sreen species that used to develop the Silk Route and establish quality standards.Finally, We get conclusions are as follows. First, primary,.prosperous and declining stages of development of exotic traditional medicine are Qin and Han, Song-Jin-Yuan, Ming and Qing Dynasties, respectively. Second, according to literature, the stage that has the most species of exotic medicine is song dynasty,approximately have 300. Removing repeating and doubtful species, the believable species are approximate 230 to 250. Meanwhile, the unknown species are approximate 30, which may be different name of one medicine or processed goods, now these medicines are named as "doubtful species". Third, the medicinal parts of exotic medicine are different from Chinese medicine of Han nation. The number of Resin, fruits and seeds kind are more than root and rhizomes kind,mineral medicines are more than animal. Fourth, the major producing area of exotic medicine is some countries and territories related to the Silk Route in the history. Ultimately, this paper preliminarily figure out basic information of exotic medicine of different dynasty in China,that provide reference for learning study and decision of industrial development. Copyright© by the Chinese Pharmaceutical Association.

The 'disector' a tool for quantitative assessment of synaptic plasticity an example on hippocampal synapses and synapse-perforations in ageing rats

NARCIS (Netherlands)

Groot, D.M.G. de; Bierman, E.P.B.; Bruijnzeel, P.L.B.; Woutersen, R.A.

1995-01-01

The 'disector' method was used to estimate number and size of simple non-perforated and complex 'perforated' synapses and their 'perforations' in the hippocampal CA3 area of 3, 12, 24 and 30 months old rats. A decrease with age from 3 to 24 months of age in the number of non-perforated synapses per

Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers.

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Park, Dongseok; Bae, Sungwon; Yoon, Taek Han; Ko, Jaewon

2018-04-18

Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.

Synaptic communication between neurons and NG2+ cells.

Science.gov (United States)

Paukert, Martin; Bergles, Dwight E

2006-10-01

Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.

Stabilization of memory States by stochastic facilitating synapses.

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Miller, Paul

2013-12-06

Bistability within a small neural circuit can arise through an appropriate strength of excitatory recurrent feedback. The stability of a state of neural activity, measured by the mean dwelling time before a noise-induced transition to another state, depends on the neural firing-rate curves, the net strength of excitatory feedback, the statistics of spike times, and increases exponentially with the number of equivalent neurons in the circuit. Here, we show that such stability is greatly enhanced by synaptic facilitation and reduced by synaptic depression. We take into account the alteration in times of synaptic vesicle release, by calculating distributions of inter-release intervals of a synapse, which differ from the distribution of its incoming interspike intervals when the synapse is dynamic. In particular, release intervals produced by a Poisson spike train have a coefficient of variation greater than one when synapses are probabilistic and facilitating, whereas the coefficient of variation is less than one when synapses are depressing. However, in spite of the increased variability in postsynaptic input produced by facilitating synapses, their dominant effect is reduced synaptic efficacy at low input rates compared to high rates, which increases the curvature of neural input-output functions, leading to wider regions of bistability in parameter space and enhanced lifetimes of memory states. Our results are based on analytic methods with approximate formulae and bolstered by simulations of both Poisson processes and of circuits of noisy spiking model neurons.

Advances in synapse formation: forging connections in the worm.

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Cherra, Salvatore J; Jin, Yishi

2015-01-01

Synapse formation is the quintessential process by which neurons form specific connections with their targets to enable the development of functional circuits. Over the past few decades, intense research efforts have identified thousands of proteins that localize to the pre- and postsynaptic compartments. Genetic dissection has provided important insights into the nexus of the molecular and cellular network, and has greatly advanced our knowledge about how synapses form and function physiologically. Moreover, recent studies have highlighted the complex regulation of synapse formation with the identification of novel mechanisms involving cell interactions from non-neuronal sources. In this review, we cover the conserved pathways required for synaptogenesis and place specific focus on new themes of synapse modulation arising from studies in Caenorhabditis elegans. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 Wiley Periodicals, Inc.

Shaping Synapses by the Neural Extracellular Matrix

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Maura Ferrer-Ferrer

2018-05-01

Full Text Available Accumulating data support the importance of interactions between pre- and postsynaptic neuronal elements with astroglial processes and extracellular matrix (ECM for formation and plasticity of chemical synapses, and thus validate the concept of a tetrapartite synapse. Here we outline the major mechanisms driving: (i synaptogenesis by secreted extracellular scaffolding molecules, like thrombospondins (TSPs, neuronal pentraxins (NPs and cerebellins, which respectively promote presynaptic, postsynaptic differentiation or both; (ii maturation of synapses via reelin and integrin ligands-mediated signaling; and (iii regulation of synaptic plasticity by ECM-dependent control of induction and consolidation of new synaptic configurations. Particularly, we focused on potential importance of activity-dependent concerted activation of multiple extracellular proteases, such as ADAMTS4/5/15, MMP9 and neurotrypsin, for permissive and instructive events in synaptic remodeling through localized degradation of perisynaptic ECM and generation of proteolytic fragments as inducers of synaptic plasticity.

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

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Anton-Sanchez, Laura; Bielza, Concha; Merchán-Pérez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Larrañaga, Pedro

2014-01-01

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers. PMID:25206325

Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses.

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Cabezas, Carolina; Buño, Washington

2006-05-01

Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.

Silverization of China during the Ming-Qing Transition (ca. 1550-1700) and the Consequences for Research into the Babylonian Economy

NARCIS (Netherlands)

van Leeuwen, Bas; XU, Yi; Kleber, Kristin; Pirngruber, Reinhard

2016-01-01

In a recent publication, Prof. Van der Spek (2011) made an intriguing comparison between the flows of silver in the Chinese economy at the end of the Ming dynasty and in Babylonia ca. 400-60 BC. He concluded that in China the expansion of the silver economy worked positively for economic growth,

Elucidating the role of AII amacrine cells in glutamatergic retinal waves.

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Firl, Alana; Ke, Jiang-Bin; Zhang, Lei; Fuerst, Peter G; Singer, Joshua H; Feller, Marla B

2015-01-28

Spontaneous retinal activity mediated by glutamatergic neurotransmission-so-called "Stage 3" retinal waves-drives anti-correlated spiking in ON and OFF RGCs during the second week of postnatal development of the mouse. In the mature retina, the activity of a retinal interneuron called the AII amacrine cell is responsible for anti-correlated spiking in ON and OFF α-RGCs. In mature AIIs, membrane hyperpolarization elicits bursting behavior. Here, we postulated that bursting in AIIs underlies the initiation of glutamatergic retinal waves. We tested this hypothesis by using two-photon calcium imaging of spontaneous activity in populations of retinal neurons and by making whole-cell recordings from individual AIIs and α-RGCs in in vitro preparations of mouse retina. We found that AIIs participated in retinal waves, and that their activity was correlated with that of ON α-RGCs and anti-correlated with that of OFF α-RGCs. Though immature AIIs lacked the complement of membrane conductances necessary to generate bursting, pharmacological activation of the M-current, a conductance that modulates bursting in mature AIIs, blocked retinal wave generation. Interestingly, blockade of the pacemaker conductance Ih, a conductance absent in AIIs but present in both ON and OFF cone bipolar cells, caused a dramatic loss of spatial coherence of spontaneous activity. We conclude that during glutamatergic waves, AIIs act to coordinate and propagate activity generated by BCs rather than to initiate spontaneous activity. Copyright © 2015 the authors 0270-6474/15/351675-12$15.00/0.

Absence of Tangentially Migrating Glutamatergic Neurons in the Developing Avian Brain

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Fernando García-Moreno

2018-01-01

Full Text Available Summary: Several neuronal populations orchestrate neocortical development during mammalian embryogenesis. These include the glutamatergic subplate-, Cajal-Retzius-, and ventral pallium-derived populations, which coordinate cortical wiring, migration, and proliferation, respectively. These transient populations are primarily derived from other non-cortical pallial sources that migrate to the dorsal pallium. Are these migrations to the dorsal pallium conserved in amniotes or are they specific to mammals? Using in ovo electroporation, we traced the entire lineage of defined chick telencephalic progenitors. We found that several pallial sources that produce tangential migratory neurons in mammals only produced radially migrating neurons in the avian brain. Moreover, ectopic expression of VP-specific mammalian Dbx1 in avian brains altered neurogenesis but did not convert the migration into a mammal-like tangential movement. Together, these data indicate that tangential cellular contributions of glutamatergic neurons originate from outside the dorsal pallium and that pallial Dbx1 expression may underlie the generation of the mammalian neocortex during evolution. : Neocortical formation crucially depends on the early tangential arrival of several transient glutamatergic neuronal populations. García-Moreno et al. find that these neuronal migrations are absent in the developing brain of chicks. The mammalian uniqueness of these developing migrations suggests a crucial role of these cells in the evolutionary origin of the neocortex. Keywords: neocortex, chick, pallium, ventral pallium, evo-devo, evolution, Dbx1, telencephalon

Alterations in the properties of neonatal thalamocortical synapses with time in in vitro slices.

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Liliana L Luz

Full Text Available New synapses are constantly being generated and lost in the living brain with only a subset of these being stabilized to form an enduring component of neuronal circuitry. The properties of synaptic transmission have primarily been established in a variety of in vitro neuronal preparations. It is not clear, however, if newly-formed and persistent synapses contribute to the results of these studies consistently throughout the lifespan of these preparations. In neonatal somatosensory, barrel, cortex we have previously hypothesized that a population of thalamocortical synapses displaying unusually slow kinetics represent newly-formed, default-transient synapses. This clear phenotype would provide an ideal tool to investigate if such newly formed synapses consistently contribute to synaptic transmission throughout a normal experimental protocol. We show that the proportion of synapses recorded in vitro displaying slow kinetics decreases with time after brain slice preparation. However, slow synapses persist in vitro in the presence of either minocycline, an inhibitor of microglia-mediated synapse elimination, or the TrkB agonist 7,8-dihydroxyflavone a promoter of synapse formation. These findings show that the observed properties of synaptic transmission may systematically change with time in vitro in a standard brain slice preparation.

A Reaction-Diffusion Model for Synapse Growth and Long-Term Memory

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Liu, Kang; Lisman, John; Hagan, Michael

Memory storage involves strengthening of synaptic transmission known as long-term potentiation (LTP). The late phase of LTP is associated with structural processes that enlarge the synapse. Yet, synapses must be stable, despite continual subunit turnover, over the lifetime of an encoded memory. These considerations suggest that synapses are variable-size stable structure (VSSS), meaning they can switch between multiple metastable structures with different sizes. The mechanisms underlying VSSS are poorly understood. While experiments and theory have suggested that the interplay between diffusion and receptor-scaffold interactions can lead to a preferred stable size for synaptic domains, such a mechanism cannot explain how synapses adopt widely different sizes. Here we develop a minimal reaction-diffusion model of VSSS for synapse growth, incorporating the recent observation from super-resolution microscopy that neural activity can build compositional heterogeneities within synaptic domains. We find that introducing such heterogeneities can change the stable domain size in a controlled manner. We discuss a potential connection between this model and experimental data on synapse sizes, and how it provides a possible mechanism to structurally encode graded long-term memory. We acknowledge the support from NSF INSPIRE Award number IOS-1526941 (KL, MFH, JL) and the Brandeis Center for Bioinspired Soft Materials, an NSF MRSEC, DMR- 1420382 (MFH).

A compound memristive synapse model for statistical learning through STDP in spiking neural networks

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Johannes eBill

2014-12-01

Full Text Available Memristors have recently emerged as promising circuit elements to mimic the function of biological synapses in neuromorphic computing. The fabrication of reliable nanoscale memristive synapses, that feature continuous conductance changes based on the timing of pre- and postsynaptic spikes, has however turned out to be challenging. In this article, we propose an alternative approach, the compound memristive synapse, that circumvents this problem by the use of memristors with binary memristive states. A compound memristive synapse employs multiple bistable memristors in parallel to jointly form one synapse, thereby providing a spectrum of synaptic efficacies. We investigate the computational implications of synaptic plasticity in the compound synapse by integrating the recently observed phenomenon of stochastic filament formation into an abstract model of stochastic switching. Using this abstract model, we first show how standard pulsing schemes give rise to spike-timing dependent plasticity (STDP with a stabilizing weight dependence in compound synapses. In a next step, we study unsupervised learning with compound synapses in networks of spiking neurons organized in a winner-take-all architecture. Our theoretical analysis reveals that compound-synapse STDP implements generalized Expectation-Maximization in the spiking network. Specifically, the emergent synapse configuration represents the most salient features of the input distribution in a Mixture-of-Gaussians generative model. Furthermore, the network’s spike response to spiking input streams approximates a well-defined Bayesian posterior distribution. We show in computer simulations how such networks learn to represent high-dimensional distributions over images of handwritten digits with high fidelity even in presence of substantial device variations and under severe noise conditions. Therefore, the compound memristive synapse may provide a synaptic design principle for future neuromorphic

A compound memristive synapse model for statistical learning through STDP in spiking neural networks.

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Bill, Johannes; Legenstein, Robert

2014-01-01

Memristors have recently emerged as promising circuit elements to mimic the function of biological synapses in neuromorphic computing. The fabrication of reliable nanoscale memristive synapses, that feature continuous conductance changes based on the timing of pre- and postsynaptic spikes, has however turned out to be challenging. In this article, we propose an alternative approach, the compound memristive synapse, that circumvents this problem by the use of memristors with binary memristive states. A compound memristive synapse employs multiple bistable memristors in parallel to jointly form one synapse, thereby providing a spectrum of synaptic efficacies. We investigate the computational implications of synaptic plasticity in the compound synapse by integrating the recently observed phenomenon of stochastic filament formation into an abstract model of stochastic switching. Using this abstract model, we first show how standard pulsing schemes give rise to spike-timing dependent plasticity (STDP) with a stabilizing weight dependence in compound synapses. In a next step, we study unsupervised learning with compound synapses in networks of spiking neurons organized in a winner-take-all architecture. Our theoretical analysis reveals that compound-synapse STDP implements generalized Expectation-Maximization in the spiking network. Specifically, the emergent synapse configuration represents the most salient features of the input distribution in a Mixture-of-Gaussians generative model. Furthermore, the network's spike response to spiking input streams approximates a well-defined Bayesian posterior distribution. We show in computer simulations how such networks learn to represent high-dimensional distributions over images of handwritten digits with high fidelity even in presence of substantial device variations and under severe noise conditions. Therefore, the compound memristive synapse may provide a synaptic design principle for future neuromorphic architectures.

Wu-Chia-Pi Solution Attenuates Carbon Tetrachloride-Induced Hepatic Injury through the Antioxidative Abilities of Its Components Acteoside and Quercetin

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Ching-Chiung Wang

2012-12-01

Full Text Available Wu-Chia-Pi medicated wine, composed nine Chinese medicines soaked in 35% alcohol, is widely used in Asia for its health-promoting functions. However, long-term consumption of alcohol could result in liver dysfunction. In this study, Wu-Chia-Pi solution (WCPS and extract (WCPE were prepared by modification of the principals given by the Committee on Chinese Medicine and Pharmacy in Taiwan. The aim of this study was to explore the protective effect of WCPS against carbon tetrachloride (CCl4-induced liver injury and to clarify its active component(s. Antioxidative effects of the test samples were evaluated via MDA inhibition, catalase activity and DPPH-scavenging assays. HPLC was used to analysis the active components. Results showed that WCPS (1 and 5 mL/kg significantly prevented CCl4-induced liver injury without chronic liver toxicity. Referring to the antioxidative activities, WCPE displayed significant MDA inhibitory and DPPH-scavenging activities with IC50 values of 0.91 ± 0.03 and 0.60 ± 0.04 mg/mL, respectively. Catalase activity was also enhanced by treatment of WCPE, acteoside and quercetin. Therefore, we suggest that acteoside and quercetin are the major contributors to the antioxidative and hepatoprotective activities of WCPS, and a possible mechanism could be mediated through reduction of oxidative stress.

The immunological synapse: a focal point for endocytosis and exocytosis.

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Griffiths, Gillian M; Tsun, Andy; Stinchcombe, Jane C

2010-05-03

There are many different cells in the immune system. To mount an effective immune response, they need to communicate with each other. One way in which this is done is by the formation of immunological synapses between cells. Recent developments show that the immune synapse serves as a focal point for exocytosis and endocytosis, directed by centrosomal docking at the plasma membrane. In this respect, formation of the immunological synapse bears striking similarities to cilia formation and cytokinesis. These intriguing observations suggest that the centrosome may play a conserved role in designating a specialized area of membrane for localized endocytosis and exocytosis.

Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.

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Adel Zeidan

Full Text Available Neuroligins (Nlgns are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8-12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.

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

Research on the Distribution and Characteristics of Moso Ethnic Costume during the Ming and Qing Dynasties

Institute of Scientific and Technical Information of China (English)

YANG Linjun

2014-01-01

The “Moso” (麽些) during the Ming and Qing dynasties includes present day Naxi, as well as the present day Mongolians in the areas of Muli, Yanyuan, and the “Nari” and“Namuyi” branches of the Tibetan . The Moso were distributed in the present day area of Lijiang , Diqing, Nujiang;the Mangkang area of Changdu;the Muli, Yanyuan, and Yanbian areas of Liangs-han Prefecture; and Batang and Litang of Ganzi Prefecture .Due to the special geographic environ-ment as well as policies implemented by various dynasties regarding the ethnic people in the border areas, the Moso formed a kind of culture with their own characteristics during the long process of histo-ry.In different historical periods , the Moso's cos-tume and culture also differed-some parts there were passed down , but there was also innovation and development .The regional characteristics of the Moso costume were obvious during the Ming and Qing dynasties.This article, from the perspec-tive historical geography , will discuss the geo-graphical distribution , evolution and formation of Moso costume during the Ming and Qing periods . 　　Costume is a marker of an “ethnic group” , and it includes both clothes and ornaments .Seen from the vertical line of history , the costume of Moso people has various characteristics in various periods;and seen from the horizontal line of histo-ry, the costume has very obvious regional differ-ences.There are few records on Moso costumes before the Ming dynasty .Only a few records are found, for example, in the shiji· xinanyi liezhuan ( An Account of the Southwestern Yi in The Records of the Historian) , xintangshu· nanman zhuan ( An Account of the Southern Barbarians in the New Tang History) .Since the Ming dynasty , there are more records about the Moso in Han Chinese litera-ture in which new characteristics of Moso costume could be noted .A kind of regional distribution of Moso costume appeared , including the Lijiang cos-tume zone , and the Yanyuan

Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

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Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

2009-03-01

Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

Glutamatergic neurotransmission from melanopsin retinal ganglion cells is required for neonatal photoaversion but not adult pupillary light reflex.

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Anton Delwig

Full Text Available Melanopsin-expressing retinal ganglion cells (mRGCs in the eye play an important role in many light-activated non-image-forming functions including neonatal photoaversion and the adult pupillary light reflex (PLR. MRGCs rely on glutamate and possibly PACAP (pituitary adenylate cyclase-activating polypeptide to relay visual signals to the brain. However, the role of these neurotransmitters for individual non-image-forming responses remains poorly understood. To clarify the role of glutamatergic signaling from mRGCs in neonatal aversion to light and in adult PLR, we conditionally deleted vesicular glutamate transporter (VGLUT2 selectively from mRGCs in mice. We found that deletion of VGLUT2 in mRGCs abolished negative phototaxis and light-induced distress vocalizations in neonatal mice, underscoring a necessary role for glutamatergic signaling. In adult mice, loss of VGLUT2 in mRGCs resulted in a slow and an incomplete PLR. We conclude that glutamatergic neurotransmission from mRGCs is required for neonatal photoaversion but is complemented by another non-glutamatergic signaling mechanism for the pupillary light reflex in adult mice. We speculate that this complementary signaling might be due to PACAP neurotransmission from mRGCs.

Analog memristive synapse in spiking networks implementing unsupervised learning

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Erika Covi

2016-10-01

Full Text Available Emerging brain-inspired architectures call for devices that can emulate the functionality of biological synapses in order to implement new efficient computational schemes able to solve ill-posed problems. Various devices and solutions are still under investigation and, in this respect, a challenge is opened to the researchers in the field. Indeed, the optimal candidate is a device able to reproduce the complete functionality of a synapse, i.e. the typical synaptic process underlying learning in biological systems (activity-dependent synaptic plasticity. This implies a device able to change its resistance (synaptic strength, or weight upon proper electrical stimuli (synaptic activity and showing several stable resistive states throughout its dynamic range (analog behavior. Moreover, it should be able to perform spike timing dependent plasticity (STDP, an associative homosynaptic plasticity learning rule based on the delay time between the two firing neurons the synapse is connected to. This rule is a fundamental learning protocol in state-of-art networks, because it allows unsupervised learning. Notwithstanding this fact, STDP-based unsupervised learning has been proposed several times mainly for binary synapses rather than multilevel synapses composed of many binary memristors. This paper proposes an HfO2-based analog memristor as a synaptic element which performs STDP within a small spiking neuromorphic network operating unsupervised learning for character recognition. The trained network is able to recognize five characters even in case incomplete or noisy characters are displayed and it is robust to a device-to-device variability of up to +/-30%.

Analog Memristive Synapse in Spiking Networks Implementing Unsupervised Learning.

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Covi, Erika; Brivio, Stefano; Serb, Alexander; Prodromakis, Themis; Fanciulli, Marco; Spiga, Sabina

2016-01-01

Emerging brain-inspired architectures call for devices that can emulate the functionality of biological synapses in order to implement new efficient computational schemes able to solve ill-posed problems. Various devices and solutions are still under investigation and, in this respect, a challenge is opened to the researchers in the field. Indeed, the optimal candidate is a device able to reproduce the complete functionality of a synapse, i.e., the typical synaptic process underlying learning in biological systems (activity-dependent synaptic plasticity). This implies a device able to change its resistance (synaptic strength, or weight) upon proper electrical stimuli (synaptic activity) and showing several stable resistive states throughout its dynamic range (analog behavior). Moreover, it should be able to perform spike timing dependent plasticity (STDP), an associative homosynaptic plasticity learning rule based on the delay time between the two firing neurons the synapse is connected to. This rule is a fundamental learning protocol in state-of-art networks, because it allows unsupervised learning. Notwithstanding this fact, STDP-based unsupervised learning has been proposed several times mainly for binary synapses rather than multilevel synapses composed of many binary memristors. This paper proposes an HfO 2 -based analog memristor as a synaptic element which performs STDP within a small spiking neuromorphic network operating unsupervised learning for character recognition. The trained network is able to recognize five characters even in case incomplete or noisy images are displayed and it is robust to a device-to-device variability of up to ±30%.

LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

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Ji Won Um

2016-02-01

Full Text Available The four members of the LRRTM family (LRRTM1-4 are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.

Salsolinol facilitates glutamatergic transmission to dopamine neurons in the posterior ventral tegmental area of rats.

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Guiqin Xie

Full Text Available Although in vivo evidence indicates that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse, the underlying mechanisms have not been fully elucidated. We have reported previously that salsolinol stimulates dopamine neurons in the posterior ventral tegmental area (p-VTA partly by reducing inhibitory GABAergic transmission, and that ethanol increases glutamatergic transmission to VTA-dopamine neurons via the activation of dopamine D(1 receptors (D(1Rs. In this study, we tested the hypothesis that salsolinol stimulates dopamine neurons involving activation of D(1Rs. By using whole-cell recordings on p-VTA-dopamine neurons in acute brain slices of rats, we found that salsolinol-induced increase in spike frequency of dopamine neurons was substantially attenuated by DL-2-amino-5-phosphono-valeric acid and 6, 7-dinitroquinoxaline-2, 3-dione, the antagonists of glutamatergic N-Methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Moreover, salsolinol increased the amplitude of evoked excitatory postsynaptic currents (EPSCs and the frequency but not the amplitude of spontaneous EPSCs. Additionally, SKF83566, a D(1R antagonist attenuated the salsolinol-induced facilitation of EPSCs and of spontaneous firing of dopamine neurons. Our data reveal that salsolinol enhances glutamatergic transmission onto dopamine neurons via activation of D(1Rs at the glutamatergic afferents in dopamine neurons, which contributes to salsolinol's stimulating effect on p-VTA dopamine neurons. This appears to be a novel mechanism which contributes toward rewarding properties of salsolinol.

Dynamic Information Encoding With Dynamic Synapses in Neural Adaptation

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Li, Luozheng; Mi, Yuanyuan; Zhang, Wenhao; Wang, Da-Hui; Wu, Si

2018-01-01

Adaptation refers to the general phenomenon that the neural system dynamically adjusts its response property according to the statistics of external inputs. In response to an invariant stimulation, neuronal firing rates first increase dramatically and then decrease gradually to a low level close to the background activity. This prompts a question: during the adaptation, how does the neural system encode the repeated stimulation with attenuated firing rates? It has been suggested that the neural system may employ a dynamical encoding strategy during the adaptation, the information of stimulus is mainly encoded by the strong independent spiking of neurons at the early stage of the adaptation; while the weak but synchronized activity of neurons encodes the stimulus information at the later stage of the adaptation. The previous study demonstrated that short-term facilitation (STF) of electrical synapses, which increases the synchronization between neurons, can provide a mechanism to realize dynamical encoding. In the present study, we further explore whether short-term plasticity (STP) of chemical synapses, an interaction form more common than electrical synapse in the cortex, can support dynamical encoding. We build a large-size network with chemical synapses between neurons. Notably, facilitation of chemical synapses only enhances pair-wise correlations between neurons mildly, but its effect on increasing synchronization of the network can be significant, and hence it can serve as a mechanism to convey the stimulus information. To read-out the stimulus information, we consider that a downstream neuron receives balanced excitatory and inhibitory inputs from the network, so that the downstream neuron only responds to synchronized firings of the network. Therefore, the response of the downstream neuron indicates the presence of the repeated stimulation. Overall, our study demonstrates that STP of chemical synapse can serve as a mechanism to realize dynamical neural

Synapse-specific astrocyte gating of amygdala-related behavior.

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Martin-Fernandez, Mario; Jamison, Stephanie; Robin, Laurie M; Zhao, Zhe; Martin, Eduardo D; Aguilar, Juan; Benneyworth, Michael A; Marsicano, Giovanni; Araque, Alfonso

2017-11-01

The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A 1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

Neuromorphic function learning with carbon nanotube based synapses

International Nuclear Information System (INIS)

Gacem, Karim; Filoramo, Arianna; Derycke, Vincent; Retrouvey, Jean-Marie; Chabi, Djaafar; Zhao, Weisheng; Klein, Jacques-Olivier

2013-01-01

The principle of using nanoscale memory devices as artificial synapses in neuromorphic circuits is recognized as a promising way to build ground-breaking circuit architectures tolerant to defects and variability. Yet, actual experimental demonstrations of the neural network type of circuits based on non-conventional/non-CMOS memory devices and displaying function learning capabilities remain very scarce. We show here that carbon-nanotube-based memory elements can be used as artificial synapses, combined with conventional neurons and trained to perform functions through the application of a supervised learning algorithm. The same ensemble of eight devices can notably be trained multiple times to code successively any three-input linearly separable Boolean logic function despite device-to-device variability. This work thus represents one of the very few demonstrations of actual function learning with synapses based on nanoscale building blocks. The potential of such an approach for the parallel learning of multiple and more complex functions is also evaluated. (paper)

Synchronization of the small-world neuronal network with unreliable synapses

International Nuclear Information System (INIS)

Li, Chunguang; Zheng, Qunxian

2010-01-01

As is well known, synchronization phenomena are ubiquitous in neuronal systems. Recently a lot of work concerning the synchronization of the neuronal network has been accomplished. In these works, the synapses are usually considered reliable, but experimental results show that, in biological neuronal networks, synapses are usually unreliable. In our previous work, we have studied the synchronization of the neuronal network with unreliable synapses; however, we have not paid attention to the effect of topology on the synchronization of the neuronal network. Several recent studies have found that biological neuronal networks have typical properties of small-world networks, characterized by a short path length and high clustering coefficient. In this work, mainly based on the small-world neuronal network (SWNN) with inhibitory neurons, we study the effect of network topology on the synchronization of the neuronal network with unreliable synapses. Together with the network topology, the effects of the GABAergic reversal potential, time delay and noise are also considered. Interestingly, we found a counter-intuitive phenomenon for the SWNN with specific shortcut adding probability, that is, the less reliable the synapses, the better the synchronization performance of the SWNN. We also consider the effects of both local noise and global noise in this work. It is shown that these two different types of noise have distinct effects on the synchronization: one is negative and the other is positive

Spatially restricted actin-regulatory signaling contributes to synapse morphology

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Nicholson, Daniel A.; Cahill, Michael E.; Tulisiak, Christopher T.; Geinisman, Yuri; Penzes, Peter

2012-01-01

The actin cytoskeleton in dendritic spines is organized into microdomains, but how signaling molecules that regulate actin are spatially governed is incompletely understood. Here we examine how the localization of the RacGEF kalirin-7, a well-characterized regulator of actin in spines, varies as a function of postsynaptic density (PSD) area and spine volume. Using serial section electron microscopy (EM), we find that extrasynaptic, but not synaptic, expression of kalirin-7 varies directly with synapse size and spine volume. Moreover, we find that overall expression levels of kalirin-7 differ in spines bearing perforated and non-perforated synapses, due primarily to extrasynaptic pools of kalirin-7 expression in the former. Overall, our findings indicate that kalirin-7 is differentially compartmentalized in spines as a function of both synapse morphology and spine size. PMID:22458534

Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

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Uchigashima, Motokazu; Ohtsuka, Toshihisa; Kobayashi, Kazuto; Watanabe, Masahiko

2016-01-01

Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABAA receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets. PMID:27035941

Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.

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Sickmann, Helle M; Walls, Anne B; Schousboe, Arne; Bouman, Stephan D; Waagepetersen, Helle S

2009-05-01

The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.

Face classification using electronic synapses

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Yao, Peng; Wu, Huaqiang; Gao, Bin; Eryilmaz, Sukru Burc; Huang, Xueyao; Zhang, Wenqiang; Zhang, Qingtian; Deng, Ning; Shi, Luping; Wong, H.-S. Philip; Qian, He

2017-05-01

Conventional hardware platforms consume huge amount of energy for cognitive learning due to the data movement between the processor and the off-chip memory. Brain-inspired device technologies using analogue weight storage allow to complete cognitive tasks more efficiently. Here we present an analogue non-volatile resistive memory (an electronic synapse) with foundry friendly materials. The device shows bidirectional continuous weight modulation behaviour. Grey-scale face classification is experimentally demonstrated using an integrated 1024-cell array with parallel online training. The energy consumption within the analogue synapses for each iteration is 1,000 × (20 ×) lower compared to an implementation using Intel Xeon Phi processor with off-chip memory (with hypothetical on-chip digital resistive random access memory). The accuracy on test sets is close to the result using a central processing unit. These experimental results consolidate the feasibility of analogue synaptic array and pave the way toward building an energy efficient and large-scale neuromorphic system.

Exploring triacylglycerol biosynthetic pathway in developing seeds of Chia (Salvia hispanica L.: a transcriptomic approach.

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Sreedhar R V

Full Text Available Chia (Salvia hispanica L., a member of the mint family (Lamiaceae, is a rediscovered crop with great importance in health and nutrition and is also the highest known terrestrial plant source of heart-healthy omega-3 fatty acid, alpha linolenic acid (ALA. At present, there is no public genomic information or database available for this crop, hindering research on its genetic improvement through genomics-assisted breeding programs. The first comprehensive analysis of the global transcriptome profile of developing Salvia hispanica L. seeds, with special reference to lipid biosynthesis is presented in this study. RNA from five different stages of seed development was extracted and sequenced separately using the Illumina GAIIx platform. De novo assembly of processed reads in the pooled transcriptome using Trinity yielded 76,014 transcripts. The total transcript length was 66,944,462 bases (66.9 Mb, with an average length of approximately 880 bases. In the molecular functions category of Gene Ontology (GO terms, ATP binding and nucleotide binding were found to be the most abundant and in the biological processes category, the metabolic process and the regulation of transcription-DNA-dependent and oxidation-reduction process were abundant. From the EuKaryotic Orthologous Groups of proteins (KOG classification, the major category was "Metabolism" (31.97%, of which the most prominent class was 'carbohydrate metabolism and transport' (5.81% of total KOG classifications followed by 'secondary metabolite biosynthesis transport and catabolism' (5.34% and 'lipid metabolism' (4.57%. A majority of the candidate genes involved in lipid biosynthesis and oil accumulation were identified. Furthermore, 5596 simple sequence repeats (SSRs were identified. The transcriptome data was further validated through confirmative PCR and qRT-PCR for select lipid genes. Our study provides insight into the complex transcriptome and will contribute to further genome-wide research

Effects of Land Use Change on Sediment and Water Yields in Yang Ming Shan National Park, Taiwan

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Thomas C. C. Huang

2015-01-01

Full Text Available The Soil and Water Assessment Tool (SWAT is a watershed-based, semi-distributed hydrologic model for simulating hydrological processes at different spatial scales. The SWAT hydrology and erosion/sediment components are first validated after the hydrologic components calibration. The SWAT model also utilizes geographic information system (GIS and digital elevation model (DEM to delineate watersheds and extract the stream network. This study applies SWAT model to assess the impacts of land use change on soil and water losses from Yang Ming Shan National Park Watershed in northern Taiwan. Although the government has formulated regulations to limit the development, however, intense human activities, such as farming and building construction, still continue to exist. This study utilized two land-use data periods, one in 1996 and another in 2007, along with the SWAT model to simulate soil and water losses in Yang Ming Shan National Park. Based on the baseline scenario, the SWAT model was also successful in simulating the future scenario. Study results for scenario 2007, as compared to 1996 baseline period indicate that land use change shows forest land decreases about 6.9%, agricultural land increases about 9.5%, and causes sediment yield increase of 0.25 t/ha. Human activities deserve more attention when assessing soil and water losses because of their inevitable impacts. Government needs to modify land development policies and plans for land use change detection using satellite imagery to avoid illegal development activities.

Modulation, plasticity and pathophysiology of the parallel fiber-Purkinje cell synapse

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Eriola Hoxha

2016-11-01

Full Text Available The parallel fiber-Purkinje cell synapse represents the point of maximal signal divergence in the cerebellar cortex with an estimated number of about 60 billion synaptic contacts in the rat and 100,000 billions in humans. At the same time, the Purkinje cell dendritic tree is a site of remarkable convergence of more than 100,000 parallel fiber synapses. Parallel fibers activity generates fast postsynaptic currents via AMPA receptors, and slower signals, mediated by mGlu1 receptors, resulting in Purkinje cell depolarization accompanied by sharp calcium elevation within dendritic regions. Long-term depression and long-term potentiation have been widely described for the parallel fiber-Purkinje cell synapse and have been proposed as mechanisms for motor learning. The mechanisms of induction for LTP and LTD involve different signaling mechanisms within the presynaptic terminal and/or at the postsynaptic site, promoting enduring modification in the neurotransmitter release and change in responsiveness to the neurotransmitter. The parallel fiber-Purkinje cell synapse is finely modulated by several neurotransmitters, including serotonin, noradrenaline, and acetylcholine. The ability of these neuromodulators to gate LTP and LTD at the parallel fiber-Purkinje cell synapse could, at least in part, explain their effect on cerebellar-dependent learning and memory paradigms. Overall, these findings have important implications for understanding the cerebellar involvement in a series of pathological conditions, ranging from ataxia to autism. For example, parallel fiber-Purkinje cell synapse dysfunctions have been identified in several murine models of spinocerebellar ataxia (SCA types 1, 3, 5 and 27. In some cases, the defect is specific for the AMPA receptor signaling (SCA27, while in others the mGlu1 pathway is affected (SCA1, 3, 5. Interestingly, the parallel fiber-Purkinje cell synapse has been shown to be hyper-functional in a mutant mouse model of autism

Cell Adhesion, the Backbone of the Synapse: “Vertebrate” and “Invertebrate” Perspectives

OpenAIRE

Giagtzoglou, Nikolaos; Ly, Cindy V.; Bellen, Hugo J.

2009-01-01

Synapses are asymmetric intercellular junctions that mediate neuronal communication. The number, type, and connectivity patterns of synapses determine the formation, maintenance, and function of neural circuitries. The complexity and specificity of synaptogenesis relies upon modulation of adhesive properties, which regulate contact initiation, synapse formation, maturation, and functional plasticity. Disruption of adhesion may result in structural and functional imbalance that may lead to neu...

Glutamatergic model psychoses: prediction error, learning, and inference.

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Corlett, Philip R; Honey, Garry D; Krystal, John H; Fletcher, Paul C

2011-01-01

Modulating glutamatergic neurotransmission induces alterations in conscious experience that mimic the symptoms of early psychotic illness. We review studies that use intravenous administration of ketamine, focusing on interindividual variability in the profundity of the ketamine experience. We will consider this individual variability within a hypothetical model of brain and cognitive function centered upon learning and inference. Within this model, the brains, neural systems, and even single neurons specify expectations about their inputs and responding to violations of those expectations with new learning that renders future inputs more predictable. We argue that ketamine temporarily deranges this ability by perturbing both the ways in which prior expectations are specified and the ways in which expectancy violations are signaled. We suggest that the former effect is predominantly mediated by NMDA blockade and the latter by augmented and inappropriate feedforward glutamatergic signaling. We suggest that the observed interindividual variability emerges from individual differences in neural circuits that normally underpin the learning and inference processes described. The exact source for that variability is uncertain, although it is likely to arise not only from genetic variation but also from subjects' previous experiences and prior learning. Furthermore, we argue that chronic, unlike acute, NMDA blockade alters the specification of expectancies more profoundly and permanently. Scrutinizing individual differences in the effects of acute and chronic ketamine administration in the context of the Bayesian brain model may generate new insights about the symptoms of psychosis; their underlying cognitive processes and neurocircuitry.

Pursuit of Neurotransmitter Functions: Being Attracted with Fascination of the Synapse.

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Konishi, Shiro

2017-01-01

In the beginning of the 1970s, only two chemical substances, acetylcholine and γ-aminobutyric acid (GABA), had been definitely established as neurotransmitters. Under such circumstances, I started my scientific career in Professor Masanori Otsuka's lab searching for the transmitter of primary sensory neurons. Until 1976, lines of evidence had accumulated indicating that the undecapeptide substance P could be released as a transmitter from primary afferent fibers into spinal synapses, although the substance P-mediated synaptic response had yet to be identified. Peripheral synapses could serve as a good model and thus, it was demonstrated in the prevertebral sympathetic ganglia by1985 that substance P released from axon collaterals of primary sensory neurons acts as the transmitter mediating non-cholinergic slow excitatory postsynaptic potential (EPSP). At that time, we also found that autonomic synapses were useful to uncover the transmitter role of the opioid peptide enkephalins, whose functions had been unknown since their discovery in 1975. Accordingly, enkephalins were found to serve a transmitter role in mediating presynaptic inhibition of cholinergic fast and non-cholinergic slow transmission in the prevertebral sympathetic ganglia. In 1990s, we attempted to devise a combined technique of brain slices and patch-clamp recordings. We applied it to study the regulatory mechanisms that operate around cerebellar GABAergic inhibitory synapses, because most of the studies then had centered on excitatory synapses and because inhibitory synapses are crucially involved in brain functions and disorders. Consequently, we discovered novel forms of heterosynaptic interactions, dual actions of a single transmitter, and receptor crosstalk, the details of which are described in this review.

Metaplasticity at CA1 Synapses by Homeostatic Control of Presynaptic Release Dynamics

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Cary Soares

2017-10-01

Full Text Available Summary: Hebbian and homeostatic forms of plasticity operate on different timescales to regulate synaptic strength. The degree of mechanistic overlap between these processes and their mutual influence are still incompletely understood. Here, we report that homeostatic synaptic strengthening induced by prolonged network inactivity compromised the ability of CA1 synapses to exhibit LTP. This effect could not be accounted for by an obvious deficit in the postsynaptic capacity for LTP expression, since neither the fraction of silent synapses nor the ability to induce LTP by two-photon glutamate uncaging were reduced by the homeostatic process. Rather, optical quantal analysis reveals that homeostatically strengthened synapses display a reduced capacity to maintain glutamate release fidelity during repetitive stimulation, ultimately impeding the induction, and thus expression, of LTP. By regulating the short-term dynamics of glutamate release, the homeostatic process thus influences key aspects of dynamic network function and exhibits features of metaplasticity. : Several forms of synaptic plasticity operating over distinct spatiotemporal scales have been described at hippocampal synapses. Whether these distinct plasticity mechanisms interact and influence one another remains incompletely understood. Here, Soares et al. show that homeostatic plasticity induced by network silencing influences short-term release dynamics and Hebbian plasticity rules at hippocampal synapses. Keywords: synapse, LTP, homeostatic plasticity, metaplasticity, iGluSNFR

Adding a purple corn extract in rats supplemented with chia oil decreases gene expression of SREBP-1c and retains Δ5 and Δ6 hepatic desaturase activity, unmodified the hepatic lipid profile.

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Reyna Gallegos, Sixto; Torres Arrunátegui, Génesis; Valenzuela, Rodrigo; Rincón-Cervera, Miguel Ángel; Villanueva Espinoza, María Elena

2018-05-01

Flavonoids upregulate gene expression of PPAR-α and underregulate the gene expression of SREBP-1c, and their intake increases the plasmatic concentration of n-3 LC-PUFAs. However, the biological mechanisms underlying these effects have not been elucidated. In this work, the effect of oral supplementation of ALA from chia (Salvia hispanica L.) seed oil and anthocyanins from a purple corn extract (PCE) on gene expression of SREBP-1c, PPAR-α and Δ5 and Δ6 desaturases (Δ5D and Δ6D), the activity of these enzymes in the liver as well as the hepatic lipid profile were evaluated in thirty-six female Sprague Dawley rats whose diet was supplemented with olive oil (OL), chia oil (CH), olive oil and PCE (OL + PCE) or chia oil and PCE (CH + PCE). Gene expression of PPAR-α was significantly higher when supplemented with CH and CH + PCE, SREBP-1c gene expression was higher when supplemented with chia oil. CH supplementation enhanced Δ5D expression whereas no significant differences between treatments were observed concerning Δ6D gene expression. Activities of both desaturases were increased by including olive oil (OL + PCE and OL), and they were found to be higher in CH + PCE respect to CH for both enzymes. The ALA and n-3 LCPUFAs hepatic content was higher with CH, decreasing the levels of AA and n-6 LCPUFAs. It is concluded that the joint action of flavonoids such as anthocyanins and ALA show an anti-adipogenic effect. Desaturase activity was inhibited by ALA and kept by the anthocyanins from PCE, thus anthocyanins would exert a protective effect on the desaturase activity but they would not affect on its gene expression, however, high doses of ALA increased the production of its metabolites, masking the effect of PCE. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional hallmarks of GABAergic synapse maturation and the diverse roles of neurotrophins

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Rosemarie eGrantyn

2011-07-01

Full Text Available Functional impairment of the adult brain can result from deficits in the ontogeny of GABAergic synaptic transmission. Gene defects underlying autism spectrum disorders, Rett’s syndrome or some forms of epilepsy, but also a diverse set of syndromes accompanying perinatal trauma, hormonal imbalances, intake of sleep-inducing or mood-improving drugs or, quite common, alcohol intake during pregnancy can alter GABA signaling early in life. The search for therapeutically relevant endogenous molecules or exogenous compounds able to alleviate the consequences of dysfunction of GABAergic transmission in the embryonic or postnatal brain requires a clear understanding of its site- and state-dependent development. At the level of single synapses, it is necessary to discriminate between presynaptic and postsynaptic alterations, and to define parameters that can be regarded as both suitable and accessible for the quantification of developmental changes. Here we focus on the performance of GABAergic synapses in two brain structures, the hippocampus and the superior colliculus, describe some novel aspects of neurotrophin effects during the development of GABAergic synaptic transmission and examine the applicability of the following rules: 1 Synaptic transmission starts with GABA, 2 Nascent/immature GABAergic synapses operate in a ballistic mode (multivesicular release, 3 Immature synaptic terminals release vesicles with higher probability than mature synapses, 4 Immature GABAergic synapses are prone to paired pulse and tetanic depression, 5 Synapse maturation is characterized by an increasing dominance of synchronous over asynchronous release, 6 In immature neurons GABA acts as a depolarizing transmitter, 7 Synapse maturation implies IPSC shortening due to an increase in alpha1 subunit expression, 8 Extrasynaptic (tonic conductances can inhibit the development of synaptic (phasic GABA actions.

The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory

NARCIS (Netherlands)

Schmitz, Leanne J M; Klaassen, Remco V; Ruiperez-Alonso, Marta; Zamri, Azra Elia; Stroeder, Jasper; Rao-Ruiz, Priyanka; Lodder, Johannes C; van der Loo, Rolinka J; Mansvelder, Huib D; Smit, August B; Spijker, Sabine; Verhage, Matthijs

2017-01-01

Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with

Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

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Lee, Jae Ho [Institute of Tissue Regeneration Engineering (ITREN), Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Pradhan, Jonu [Department of Nanobio Medical Science, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Maskey, Dhiraj; Park, Ki Sup [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Hong, Sung Hwa [Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Suh, Myung-Whan [Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Kim, Myeung Ju, E-mail: mjukim99@dankook.ac.kr [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Ahn, Seung Cheol, E-mail: ansil67@hanmail.net [Department of Physiology, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of)

2011-02-11

Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

The Dangers of 'Warming and Replenishing' (wenbu ) during the Ming to Qing Epistemic Transition.

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de Vries, Leslie

2015-01-01

Through a case study of Zhao Xianke's One Principle through Medicine ( Yiguan ) (1617?) and Xu Dachun's (1693-1771) denouncements of this text, my article zooms in on divergent discourses on the safety and efficacy of medicinal substances and compounds in late imperial China. Although Xu Dachun's fierce attacks on the popular 'warming and replenishing' ( wenbu ) therapies can be situated in an epistemic shift from the cosmology of 'Song learning' ( songxue ) towards the philology of 'Han learning' ( hanxue ) and 'evidential research' ( kaozheng ), I argue that more complex issues were at stake as well. Changed political, social, ethical, and economic realities shaped new and multifaceted perceptions of the nature of medicine, the medical profession, and the usage of medicinals in the aftermath of the Ming to Qing transition.

Orchestrating cytoskeleton and intracellular vesicle traffic to build functional immunological synapses.

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Soares, Helena; Lasserre, Rémi; Alcover, Andrés

2013-11-01

Immunological synapses are specialized cell-cell contacts formed between T lymphocytes and antigen-presenting cells. They are induced upon antigen recognition and are crucial for T-cell activation and effector functions. The generation and function of immunological synapses depend on an active T-cell polarization process, which results from a finely orchestrated crosstalk between the antigen receptor signal transduction machinery, the actin and microtubule cytoskeletons, and controlled vesicle traffic. Although we understand how some of these particular events are regulated, we still lack knowledge on how these multiple cellular elements are harmonized to ensure appropriate T-cell responses. We discuss here our view on how T-cell receptor signal transduction initially commands cytoskeletal and vesicle traffic polarization, which in turn sets the immunological synapse molecular design that regulates T-cell activation. We also discuss how the human immunodeficiency virus (HIV-1) hijacks some of these processes impairing immunological synapse generation and function. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Asian Cross-border Marriage Migration. Demographic Patterns and Social Issues, Wen-Shan Yang & Melody Chia-Wen Lu (éds

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Jean-Pierre de Saint-Aubert

2012-11-01

Full Text Available Cet ouvrage collectif, qui est le résultat d’une collaboration entre l’International Institute for Asian Studies (IIAS, des Pays-Bas, et la National Science Council (NSC, de Taïwan, est le fruit d’une conférence qui s’est tenue en septembre2006 sur le thème des « mariages transfrontaliers en Asie et en Europe ». Les coordinateurs de l’ouvrage sont Wen-Shan Yang, chercheur à l’Institut of Sociology, Academia Sinica de Taïwan, et Melody Chia-Wen Lu, chercheur à l’International Institute for A...

Dynamic mobility of functional GABAA receptors at inhibitory synapses.

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Thomas, Philip; Mortensen, Martin; Hosie, Alastair M; Smart, Trevor G

2005-07-01

Importing functional GABAA receptors into synapses is fundamental for establishing and maintaining inhibitory transmission and for controlling neuronal excitability. By introducing a binding site for an irreversible inhibitor into the GABAA receptor alpha1 subunit channel lining region that can be accessed only when the receptor is activated, we have determined the dynamics of receptor mobility between synaptic and extrasynaptic locations in hippocampal pyramidal neurons. We demonstrate that the cell surface GABAA receptor population shows no fast recovery after irreversible inhibition. In contrast, after selective inhibition, the synaptic receptor population rapidly recovers by the import of new functional entities within minutes. The trafficking pathways that promote rapid importation of synaptic receptors do not involve insertion from intracellular pools, but reflect receptor diffusion within the plane of the membrane. This process offers the synapse a rapid mechanism to replenish functional GABAA receptors at inhibitory synapses and a means to control synaptic efficacy.

Ultralow power artificial synapses using nanotextured magnetic Josephson junctions

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Schneider, Michael L.; Donnelly, Christine A.; Russek, Stephen E.; Baek, Burm; Pufall, Matthew R.; Hopkins, Peter F.; Dresselhaus, Paul D.; Benz, Samuel P.; Rippard, William H.

2018-01-01

Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies. PMID:29387787

Kalirin, a key player in synapse formation, is implicated in human diseases.

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Mandela, Prashant; Ma, Xin-Ming

2012-01-01

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

[Discussion on professor SHAO Jing-Ming's academic opinion of focusing spirit].

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Ma, Qiao-Lin; Gao, Xi-Yan; Shao, Su-Ju; Shao, Su-Xia; Hu, Bin

2014-06-01

During professor SHAO Jing-ming's academic research and medical practice, his academic opinion of focusing spirit is gradually developed. In terms of nurturing the spirit, attention should be paid on persistence as well as everyday health maintenance and exercise to nurture the spirit of physician. In terms of clinical diagnosis and treatment, patients' psychology, employment and life status should be observed and experienced, which could bring more methods to take essential care of patients' spirit. The treatment should work with psychological counseling, advocating that based on patients' qi and spirit, various forms of treatment methods should be properly used, such as acupuncture or moxibustion or combination of acupuncture and medicine, along with simple acupoint selection and harmony medication. Before clinical treatment of acupuncture, calming the mind is critically emphasized to make a clear diagnosis. During the acupuncture, calming and focusing the mind is necessary as well as emphasizing the details, so acupuncture could be integrated with Chi Gong to create a new warming-sensation technique. In a word, the academic opinion of focusing spirit is shedding an inspiring light upon further study.

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.

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Machado, Nuno J; Simões, Ana Patrícia; Silva, Henrique B; Ardais, Ana Paula; Kaster, Manuella P; Garção, Pedro; Rodrigues, Diana I; Pochmann, Daniela; Santos, Ana Isabel; Araújo, Inês M; Porciúncula, Lisiane O; Tomé, Ângelo R; Köfalvi, Attila; Vaugeois, Jean-Marie; Agostinho, Paula; El Yacoubi, Malika; Cunha, Rodrigo A; Gomes, Catarina A

2017-03-01

Caffeine prophylactically prevents mood and memory impairments through adenosine A 2A receptor (A 2A R) antagonism. A 2A R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A 2A R density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A 2A R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A 2A R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A 2A R controlling synaptic glutamatergic function.

Large variability in synaptic N-methyl-D-aspartate receptor density on interneurons and a comparison with pyramidal-cell spines in the rat hippocampus.

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Nyíri, G; Stephenson, F A; Freund, T F; Somogyi, P

2003-01-01

Pyramidal cells receive input from several types of GABA-releasing interneurons and innervate them reciprocally. Glutamatergic activation of interneurons involves both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) type glutamate receptors expressed in type I synapses, mostly on their dendritic shafts. On average, the synaptic AMPA receptor content is several times higher on interneurons than in the spines of pyramidal cells. To compare the NMDA receptor content of synapses, we used a quantitative postembedding immunogold technique on serial electron microscopic sections, and analysed the synapses on interneuron dendrites and pyramidal cell spines in the CA1 area. Because all NMDA receptors contain the obligatory NR1 subunit, receptor localisation was carried out using antibodies recognising all splice variants of the NR1 subunit. Four populations of synapse were examined: i). on spines of pyramidal cells in stratum (str.) radiatum and str. oriens; ii). on parvalbumin-positive interneuronal dendritic shafts in str. radiatum; iii). on randomly found dendritic shafts in str. oriens and iv). on somatostatin-positive interneuronal dendritic shafts and somata in str. oriens. On average, the size of the synapses on spines was about half of those on interneurons. The four populations of synapse significantly differed in labelling for the NR1 subunit. The median density of NR1 subunit labelling was highest on pyramidal cell spines. It was lowest in the synapses on parvalbumin-positive dendrites in str. radiatum, where more than half of these synapses were immunonegative. In str. oriens, synapses on interneurons had a high variability of receptor content; some dendrites were similar to those in str. radiatum, including the proximal synapses of somatostatin-positive cells, whereas others had immunoreactivity for the NR1 subunit similar to or higher than synapses on pyramidal cell spines. These results show that synaptic NMDA

Memory and pattern storage in neural networks with activity dependent synapses

Science.gov (United States)

Mejias, J. F.; Torres, J. J.

2009-01-01

We present recently obtained results on the influence of the interplay between several activity dependent synaptic mechanisms, such as short-term depression and facilitation, on the maximum memory storage capacity in an attractor neural network [1]. In contrast with the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve activity patterns [2], synaptic facilitation is able to enhance the memory capacity in different situations. In particular, we find that a convenient balance between depression and facilitation can enhance the memory capacity, reaching maximal values similar to those obtained with static synapses, that is, without activity-dependent processes. We also argue, employing simple arguments, that this level of balance is compatible with experimental data recorded from some cortical areas, where depression and facilitation may play an important role for both memory-oriented tasks and information processing. We conclude that depressing synapses with a certain level of facilitation allow to recover the good retrieval properties of networks with static synapses while maintaining the nonlinear properties of dynamic synapses, convenient for information processing and coding.

Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

Science.gov (United States)

Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

2016-01-01

Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.

Sleep: The hebbian reinforcement of the local inhibitory synapses.

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Touzet, Claude

2015-09-01

Sleep is ubiquitous among the animal realm, and represents about 30% of our lives. Despite numerous efforts, the reason behind our need for sleep is still unknown. The Theory of neuronal Cognition (TnC) proposes that sleep is the period of time during which the local inhibitory synapses (in particular the cortical ones) are replenished. Indeed, as long as the active brain stays awake, hebbian learning guarantees that efficient inhibitory synapses lose their efficiency – just because they are efficient at avoiding the activation of the targeted neurons. Since hebbian learning is the only known mechanism of synapse modification, it follows that to replenish the inhibitory synapses' efficiency, source and targeted neurons must be activated together. This is achieved by a local depolarization that may travel (wave). The period of time during which such slow waves are experienced has been named the "slow-wave sleep" (SWS). It is cut into several pieces by shorter periods of paradoxical sleep (REM) which activity resembles that of the awake state. Indeed, SWS – because it only allows local neural activation – decreases the excitatory long distance connections strength. To avoid losing the associations built during the awake state, these long distance activations are played again during the REM sleep. REM and SWS sleeps act together to guarantee that when the subject awakes again, his inhibitory synaptic efficiency is restored and his (excitatory) long distance associations are still there. Copyright © 2015 Elsevier Ltd. All rights reserved.

Eph receptors and ephrins in neuron-astrocyte communication at synapses.

Science.gov (United States)

Murai, Keith K; Pasquale, Elena B

2011-11-01

Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease. Copyright © 2011 Wiley-Liss, Inc.

Molecular switches at the synapse emerge from receptor and kinase traffic.

Directory of Open Access Journals (Sweden)

2005-07-01

Full Text Available Changes in the synaptic connection strengths between neurons are believed to play a role in memory formation. An important mechanism for changing synaptic strength is through movement of neurotransmitter receptors and regulatory proteins to and from the synapse. Several activity-triggered biochemical events control these movements. Here we use computer models to explore how these putative memory-related changes can be stabilised long after the initial trigger, and beyond the lifetime of synaptic molecules. We base our models on published biochemical data and experiments on the activity-dependent movement of a glutamate receptor, AMPAR, and a calcium-dependent kinase, CaMKII. We find that both of these molecules participate in distinct bistable switches. These simulated switches are effective for long periods despite molecular turnover and biochemical fluctuations arising from the small numbers of molecules in the synapse. The AMPAR switch arises from a novel self-recruitment process where the presence of sufficient receptors biases the receptor movement cycle to insert still more receptors into the synapse. The CaMKII switch arises from autophosphorylation of the kinase. The switches may function in a tightly coupled manner, or relatively independently. The latter case leads to multiple stable states of the synapse. We propose that similar self-recruitment cycles may be important for maintaining levels of many molecules that undergo regulated movement, and that these may lead to combinatorial possible stable states of systems like the synapse.

Caracterização física, química e sensorial de sobremesas à base de soja, elaboradas com mucilagem de chia

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Jordana Corralo Spada

2014-02-01

Full Text Available No desenvolvimento de produtos, é de suma importância o conhecimento da influência das modificações da formulação nas propriedades sensoriais, físicas e químicas destes. O objetivo deste trabalho foi caracterizar sobremesas à base de soja com e sem adição de mucilagem de chia, utilizada como espessante alimentar. As formulações foram caracterizadas quanto as suas propriedades reológicas, °Brix, pH e cor. O perfil sensorial foi determinado por Análise Descritiva Quantitativa (ADQ, utilizando-se uma equipe de 10 julgadores treinados. Os resultados mostraram que as amostras não diferiram quanto aos valores de pH, °Brix e coordenada cromática a*. Quanto aos outros parâmetros de cor e reológicos, foram detectadas diferenças significativas entre as amostras, o que mostra a influência do tipo de espessante nestas características. Os resultados da ADQ mostraram que as amostras não apresentaram diferenças estatísticas quanto aos atributos, cor rosa, sabor de goiaba, sabor de soja e cremosidade, porém diferiram quanto à consistência. Com isso, conclui-se que a adição da mucilagem de chia pode ser feita sem causar grandes modificações ao produto.

Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

NARCIS (Netherlands)

Silva, G.; Le Bé, J.-V.; Riachi, I.; Rinaldi, T.; Markram, K.; Markram, H.

2009-01-01

A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and

Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse.

Science.gov (United States)

O'Neill, Joseph; Tobias, Marc C; Hudkins, Matthew; London, Edythe D

2014-10-31

The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment. In the methamphetamine group, small but significant (5-15%, Pright inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (Pabuse. The Beck Depression Inventory score was negatively correlated (Pright inferior frontal cortex. Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey.

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Schüz, A; Demianenko, G P

1995-01-01

Synapses and dendritic spines were investigated in the parietal cortex of the hedgehog (Erinaceus europaeus) and the monkey (Macaca mulatta). There was no significant difference in the density of synapses between the two species (14 synapses/100 microns2 in the hedgehog, 15/100 microns2 in the monkey), neither in the size of the synaptic junctions, in the proportion of Type I and Type II synapses (8-10% were of Type II in the hedgehog, 10-14% in the monkey) nor in the proportion of perforated synapses (8% in the hedgehog, 5% in the monkey). The only striking difference at the electron microscopic level concerned the frequency of synapses in which the postsynaptic profile was deeply indented into the presynaptic terminal. Such synapses were 10 times more frequent in the monkey. Dendritic spines were investigated in Golgi-preparations. The density of spines along dendrites was similar in both species. The results are discussed with regard to connectivity in the cortex of small and large brains.

Changes in rat hippocampal CA1 synapses following imipramine treatment

DEFF Research Database (Denmark)

Chen, Fenghua; Madsen, Torsten M; Wegener, Gregers

2008-01-01

Neuronal plasticity in hippocampus is hypothesized to play an important role in both the pathophysiology of depressive disorders and the treatment. In this study, we investigated the consequences of imipramine treatment on neuroplasticity (including neurogenesis, synaptogenesis, and remodelling...... and number of neurons of hippocampal subregions following imipramine treatment were found. However, the number and percentage of CA1 asymmetric spine synapses increased significantly and, conversely, the percentage of asymmetric shaft synapses significantly decreased in the imipramine treated group. Our...

Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses

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Trouche, Stéphanie; Sasaki, Jennifer M.; Tu, Tiffany; Reijmers, Leon G.

2013-01-01

SUMMARY A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. PMID:24183705

TFH-derived dopamine accelerates productive synapses in germinal centres.

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Papa, Ilenia; Saliba, David; Ponzoni, Maurilio; Bustamante, Sonia; Canete, Pablo F; Gonzalez-Figueroa, Paula; McNamara, Hayley A; Valvo, Salvatore; Grimbaldeston, Michele; Sweet, Rebecca A; Vohra, Harpreet; Cockburn, Ian A; Meyer-Hermann, Michael; Dustin, Michael L; Doglioni, Claudio; Vinuesa, Carola G

2017-07-20

Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T FH ) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T FH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human T FH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T-B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T-B-cell synapse may be advantageous in the face of infection.

NeuroD2 regulates the development of hippocampal mossy fiber synapses

Directory of Open Access Journals (Sweden)

Wilke Scott A

2012-02-01

Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

Directory of Open Access Journals (Sweden)

Isabelle Ayumi Spühler

2016-05-01

Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

Science.gov (United States)

Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

2016-07-01

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. © The Author 2016. Published by Oxford University Press.

Formas retóricas de dizer: o jornalista Celso Ming e seus artigos de opinião

OpenAIRE

Santana, Maiara Pereira de

2015-01-01

Esta dissertação, produzida na linha Texto e discurso nas modalidades oral e escrita, do Programa de Estudos em Língua Portuguesa da Pontifícia Universidade Católica de São Paulo (PUC-SP), tem por objetivo realizar uma leitura retórica de artigo opinativo, especificamente, o de domínio econômico, escrito pelo jornalista Celso Ming para o jornal O Estado de São Paulo. Para análise, adota-se a perspectiva da retórica, arte e técnica grega, que se atém aos discursos que são passíveis de persuasã...

Synapse geometry and receptor dynamics modulate synaptic strength.

Directory of Open Access Journals (Sweden)

Dominik Freche

Full Text Available Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.

Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

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Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

2014-06-01

In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development.

Science.gov (United States)

Chowdhury, Golam M I; Patel, Anant B; Mason, Graeme F; Rothman, Douglas L; Behar, Kevin L

2007-12-01

The contribution of glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons to oxidative energy metabolism and neurotransmission in the developing brain is not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused intravenously with [1,6-(13)C(2)]glucose for different time intervals (time course) or with [2-(13)C]acetate for 2 to 3 h (steady state). Amino acid levels and (13)C enrichments were determined in tissue extracts ex vivo using (1)H-[(13)C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and astroglia) to the (13)C-enrichment time courses of amino acids from [1,6-(13)C(2)]glucose, constrained by the ratios of neurotransmitter cycling (V(cyc))-to-tricarboxylic acid (TCA) cycle flux (V(TCAn)) calculated from the steady-state [2-(13)C]acetate enrichment data. From P10 to P30 increases in total neuronal (glutamate plus GABA) TCA cycle flux (3 x ; 0.24+/-0.05 versus 0.71+/-0.07 micromol per g per min, Pcycling flux (3.1 to 5 x ; 0.07 to 0.11 (+/-0.03) versus 0.34+/-0.03 micromol per g per min, Pcycling (DeltaV(cyc(tot))) and neuronal TCA cycle flux (DeltaV(TCAn(tot))) between P10 and P30 were 0.23 to 0.27 and 0.47 micromol per g per min, respectively, similar to the approximately 1:2 relationship previously reported for adult cortex. For the individual neurons, increases in V(TCAn) and V(cyc) were similar in magnitude (glutamatergic neurons, 2.7 x versus 2.8 to 4.6 x ; GABAergic neurons, approximately 5 x versus approximately 7 x), although GABAergic flux changes were larger. The findings show that glutamate and GABA neurons undergo large and approximately proportional increases in neurotransmitter cycling and oxidative energy metabolism during this major postnatal growth spurt.

Dynamic Observation of Brain-Like Learning in a Ferroelectric Synapse Device

Science.gov (United States)

Nishitani, Yu; Kaneko, Yukihiro; Ueda, Michihito; Fujii, Eiji; Tsujimura, Ayumu

2013-04-01

A brain-like learning function was implemented in an electronic synapse device using a ferroelectric-gate field effect transistor (FeFET). The FeFET was a bottom-gate type FET with a ZnO channel and a ferroelectric Pb(Zr,Ti)O3 (PZT) gate insulator. The synaptic weight, which is represented by the channel conductance of the FeFET, is updated by applying a gate voltage through a change in the ferroelectric polarization in the PZT. A learning function based on the symmetric spike-timing dependent synaptic plasticity was implemented in the synapse device using the multilevel weight update by applying a pulse gate voltage. The dynamic weighting and learning behavior in the synapse device was observed as a change in the membrane potential in a spiking neuron circuit.

Neurotensin enhances glutamatergic EPSCs in VTA neurons by acting on different neurotensin receptors.

Science.gov (United States)

Bose, Poulomee; Rompré, Pierre-Paul; Warren, Richard A

2015-11-01

Neurotensin (NT) is an endogenous neuropeptide that modulates dopamine and glutamate neurotransmission in several limbic regions innervated by neurons located in the ventral tegmental area (VTA). While several studies showed that NT exerted a direct modulation on VTA dopamine neurons less is known about its role in the modulation of glutamatergic neurotransmission in this region. The present study was aimed at characterising the effects of NT on glutamate-mediated responses in different populations of VTA neurons. Using whole cell patch clamp recording technique in horizontal rat brain slices, we measured the amplitude of glutamatergic excitatory post-synaptic currents (EPSCs) evoked by electrical stimulation of VTA afferents before and after application of different concentrations of NT1-13 or its C-terminal fragment, NT8-13. Neurons were classified as either Ih(+) or Ih(-) based on the presence or absence of a hyperpolarisation activated cationic current (Ih). We found that NT1-13 and NT8-13 produced comparable concentration dependent increase in the amplitude of EPSCs in both Ih(+) and Ih(-) neurons. In Ih(+) neurons, the enhancement effect of NT8-13 was blocked by both antagonists, while in Ih(-) neurons it was blocked by the NTS1/NTS2 antagonist, SR142948A, but not the preferred NTS1 antagonist, SR48692. In as much as Ih(-) neurons are non-dopaminergic neurons and Ih(+) neurons represent both dopamine and non-dopamine neurons, we can conclude that NT enhances glutamatergic mediated responses in dopamine, and in a subset of non-dopamine, neurons by acting respectively on NTS1 and an NT receptor other than NTS1. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

NARCIS (Netherlands)

Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

2013-01-01

The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

Artificial Synapses Based on in-Plane Gate Organic Electrochemical Transistors.

Science.gov (United States)

Qian, Chuan; Sun, Jia; Kong, Ling-An; Gou, Guangyang; Yang, Junliang; He, Jun; Gao, Yongli; Wan, Qing

2016-10-05

Realization of biological synapses using electronic devices is regarded as the basic building blocks for neuromorphic engineering and artificial neural network. With the advantages of biocompatibility, low cost, flexibility, and compatible with printing and roll-to-roll processes, the artificial synapse based on organic transistor is of great interest. In this paper, the artificial synapse simulation by ion-gel gated organic field-effect transistors (FETs) with poly(3-hexylthiophene) (P3HT) active channel is demonstrated. Key features of the synaptic behaviors, such as paired-pulse facilitation (PPF), short-term plasticity (STP), self-tuning, the spike logic operation, spatiotemporal dentritic integration, and modulation are successfully mimicked. Furthermore, the interface doping processes of electrolyte ions between the active P3HT layer and ion gels is comprehensively studied for confirming the operating processes underlying the conductivity and excitatory postsynaptic current (EPSC) variations in the organic synaptic devices. This study represents an important step toward building future artificial neuromorphic systems with newly emerged ion gel gated organic synaptic devices.

Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses.

Science.gov (United States)

Trouche, Stéphanie; Sasaki, Jennifer M; Tu, Tiffany; Reijmers, Leon G

2013-11-20

A more complete understanding of how fear extinction alters neuronal activity and connectivity within fear circuits may aid in the development of strategies to treat human fear disorders. Using a c-fos-based transgenic mouse, we found that contextual fear extinction silenced basal amygdala (BA) excitatory neurons that had been previously activated during fear conditioning. We hypothesized that the silencing of BA fear neurons was caused by an action of extinction on BA inhibitory synapses. In support of this hypothesis, we found extinction-induced target-specific remodeling of BA perisomatic inhibitory synapses originating from parvalbumin and cholecystokinin-positive interneurons. Interestingly, the predicted changes in the balance of perisomatic inhibition matched the silent and active states of the target BA fear neurons. These observations suggest that target-specific changes in perisomatic inhibitory synapses represent a mechanism through which experience can sculpt the activation patterns within a neural circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiple synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses

International Nuclear Information System (INIS)

Liu, Chen; Wang, Jiang; Wang, Lin; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok

2014-01-01

Highlights: • Synchronization transitions in hybrid scale-free neuronal networks are investigated. • Multiple synchronization transitions can be induced by the time delay. • Effect of synchronization transitions depends on the ratio of the electrical and chemical synapses. • Coupling strength and the density of inter-neuronal links can enhance the synchronization. -- Abstract: The impacts of information transmission delay on the synchronization transitions in scale-free neuronal networks with electrical and chemical hybrid synapses are investigated. Numerical results show that multiple appearances of synchronization regions transitions can be induced by different information transmission delays. With the time delay increasing, the synchronization of neuronal activities can be enhanced or destroyed, irrespective of the probability of chemical synapses in the whole hybrid neuronal network. In particular, for larger probability of electrical synapses, the regions of synchronous activities appear broader with stronger synchronization ability of electrical synapses compared with chemical ones. Moreover, it can be found that increasing the coupling strength can promote synchronization monotonously, playing the similar role of the increasing the probability of the electrical synapses. Interestingly, the structures and parameters of the scale-free neuronal networks, especially the structural evolvement plays a more subtle role in the synchronization transitions. In the network formation process, it is found that every new vertex is attached to the more old vertices already present in the network, the more synchronous activities will be emerge

Optimal and Local Connectivity Between Neuron and Synapse Array in the Quantum Dot/Silicon Brain

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Duong, Tuan A.; Assad, Christopher; Thakoor, Anikumar P.

2010-01-01

This innovation is used to connect between synapse and neuron arrays using nanowire in quantum dot and metal in CMOS (complementary metal oxide semiconductor) technology to enable the density of a brain-like connection in hardware. The hardware implementation combines three technologies: 1. Quantum dot and nanowire-based compact synaptic cell (50x50 sq nm) with inherently low parasitic capacitance (hence, low dynamic power approx.l0(exp -11) watts/synapse), 2. Neuron and learning circuits implemented in 50-nm CMOS technology, to be integrated with quantum dot and nanowire synapse, and 3. 3D stacking approach to achieve the overall numbers of high density O(10(exp 12)) synapses and O(10(exp 8)) neurons in the overall system. In a 1-sq cm of quantum dot layer sitting on a 50-nm CMOS layer, innovators were able to pack a 10(exp 6)-neuron and 10(exp 10)-synapse array; however, the constraint for the connection scheme is that each neuron will receive a non-identical 10(exp 4)-synapse set, including itself, via its efficacy of the connection. This is not a fully connected system where the 100x100 synapse array only has a 100-input data bus and 100-output data bus. Due to the data bus sharing, it poses a great challenge to have a complete connected system, and its constraint within the quantum dot and silicon wafer layer. For an effective connection scheme, there are three conditions to be met: 1. Local connection. 2. The nanowire should be connected locally, not globally from which it helps to maximize the data flow by sharing the same wire space location. 3. Each synapse can have an alternate summation line if needed (this option is doable based on the simple mask creation). The 10(exp 3)x10(exp 3)-neuron array was partitioned into a 10-block, 10(exp 2)x10(exp 3)-neuron array. This building block can be completely mapped within itself (10,000 synapses to a neuron).

Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats

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Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

2016-01-01

Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥ 0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and CNPase + and OLIG2 + oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho + oligodendrocytes were detected in the corpus callosum at ≥ 0.1%. In the dentate gyrus, CPZ at ≥ 0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1 + and GRIN2A + hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2 + granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. - Highlights: • We examined developmental cuprizone (CPZ) neurotoxicity in maternally exposed rats. • Multiple brain region-specific global gene expression profiling was performed. • CPZ decreased

Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats

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Abe, Hajime [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Tanaka, Takeshi; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Hasegawa-Baba, Yasuko [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

2016-01-01

Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥ 0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and CNPase{sup +} and OLIG2{sup +} oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho{sup +} oligodendrocytes were detected in the corpus callosum at ≥ 0.1%. In the dentate gyrus, CPZ at ≥ 0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1{sup +} and GRIN2A{sup +} hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2{sup +} granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells. - Highlights: • We examined developmental cuprizone (CPZ) neurotoxicity in maternally exposed rats. • Multiple brain region-specific global gene expression profiling

NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area.

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Racca, C; Stephenson, F A; Streit, P; Roberts, J D; Somogyi, P

2000-04-01

Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64-0.70] was much lower than that of the AMPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs.

‘Unable to think in my mother’s tongue’: immigrant daughters in Alice Pung’s 'Unpolished Gem' and Hsu-Ming Teo’s 'Behind the Moon'

Directory of Open Access Journals (Sweden)

Alice Healy

2010-05-01

Full Text Available This paper explores ‘the immigrant’s story in translation’ through the various instances of language spoken between parents and children. It analyses the experience of immigrant daughters in two ‘Asian-Australian’ texts – Alice Pung’s recent memoir Unpolished Gem and Hsu-Ming Teo’s Behind the Moon. I position these texts in the context of the reception of literature labelled ‘Asian-Australian’ in the market, exploring Hsu-Ming Teo’s critique of such positioning. Centrally, the paper examines language in all the traditions and moral understandings that language applies, the transformative speech acts between parent and child, and the creative exploration of English as a spectre re-enforcing ‘white nationalism’.The experience of first generation Chinese Australians, in particular Chinese-Singaporeans, Chinese-Malaysians and Chinese-Cambodians, are explored in a reading of this novel and memoir. The point of connection between them is the very different languages between the generations, to the extent that the daughters think in different languages to their mothers, hence a shift in perceiving the world (and society around them.

Enhanced synaptic activity and epileptiform events in the embryonic Kcc2 deficient hippocampus

Directory of Open Access Journals (Sweden)

Ilgam eKhalilov

2011-11-01

Full Text Available The neuronal potassium-chloride co-transporter Kcc2 is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2+/+ and Kcc2 deficient (Kcc2-/- mouse embryos, we unexpectedly found increased spontaneous neuronal network activity at E18.5, a developmental stage when Kcc2 is thought not to be functional in the hippocampus. Embryonic Kcc2-/- hippocampi have also an augmented synapse density and a higher frequency of spontaneous glutamatergic and GABAergic postsynaptic currents (PSCs than naïve age matched neurons. However, intracellular chloride concentration ([Cl-]i and the reversal potential of GABA-mediated currents (EGABA were similar in embryonic Kcc2+/+ and Kcc2-/- CA3 neurons. In addition, Kcc2 immuno-labelling was cytoplasmic in the majority of neurons suggesting that the molecule is not functional as a plasma membrane chloride co-transporter. Collectively, our results show that already at an embryonic stage, Kcc2 controls the formation of synapses and, when deleted, the hippocampus has a higher density of GABAergic and glutamatergic synapses and generates spontaneous and evoked epileptiform activities. These results may be explained either by a small population of orchestrating neurons in which Kcc2 operates early as a chloride exporter or by transporter independent actions of Kcc2 that are instrumental in synapses formation and networks construction.

A systematic random sampling scheme optimized to detect the proportion of rare synapses in the neuropil.

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da Costa, Nuno Maçarico; Hepp, Klaus; Martin, Kevan A C

2009-05-30

Synapses can only be morphologically identified by electron microscopy and this is often a very labor-intensive and time-consuming task. When quantitative estimates are required for pathways that contribute a small proportion of synapses to the neuropil, the problems of accurate sampling are particularly severe and the total time required may become prohibitive. Here we present a sampling method devised to count the percentage of rarely occurring synapses in the neuropil using a large sample (approximately 1000 sampling sites), with the strong constraint of doing it in reasonable time. The strategy, which uses the unbiased physical disector technique, resembles that used in particle physics to detect rare events. We validated our method in the primary visual cortex of the cat, where we used biotinylated dextran amine to label thalamic afferents and measured the density of their synapses using the physical disector method. Our results show that we could obtain accurate counts of the labeled synapses, even when they represented only 0.2% of all the synapses in the neuropil.

Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL

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Jenkins, Misty R; Stinchcombe, Jane C; Au-Yeung, Byron B; Asano, Yukako; Ritter, Alex T; Weiss, Arthur; Griffiths, Gillian M

2014-01-01

T cell receptor (TCR) activation leads to a dramatic reorganisation of both membranes and receptors as the immunological synapse forms. Using a genetic model to rapidly inhibit Zap70 catalytic activity we examined synapse formation between cytotoxic T lymphocytes and their targets. In the absence of Zap70 catalytic activity Vav-1 activation occurs and synapse formation is arrested at a stage with actin and integrin rich interdigitations forming the interface between the two cells. The membranes at the synapse are unable to flatten to provide extended contact, and Lck does not cluster to form the central supramolecular activation cluster (cSMAC). Centrosome polarisation is initiated but aborts before reaching the synapse and the granules do not polarise. Our findings reveal distinct roles for Zap70 as a structural protein regulating integrin-mediated control of actin vs its catalytic activity that regulates TCR-mediated control of actin and membrane remodelling during formation of the immunological synapse. DOI: http://dx.doi.org/10.7554/eLife.01310.001 PMID:24596147

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

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Chalmers, D.T.; Dewar, D.; Graham, D.I.; Brooks, D.N.; McCulloch, J.

1990-01-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others

Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition.

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Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F; Zhang, Ruli; Koshiya, Naohiro; Smith, Jeffrey C

2016-01-01

The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property.

Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

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Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

2016-01-01

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

Neural circuit rewiring: insights from DD synapse remodeling.

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Kurup, Naina; Jin, Yishi

2016-01-01

Nervous systems exhibit many forms of neuronal plasticity during growth, learning and memory consolidation, as well as in response to injury. Such plasticity can occur across entire nervous systems as with the case of insect metamorphosis, in individual classes of neurons, or even at the level of a single neuron. A striking example of neuronal plasticity in C. elegans is the synaptic rewiring of the GABAergic Dorsal D-type motor neurons during larval development, termed DD remodeling. DD remodeling entails multi-step coordination to concurrently eliminate pre-existing synapses and form new synapses on different neurites, without changing the overall morphology of the neuron. This mini-review focuses on recent advances in understanding the cellular and molecular mechanisms driving DD remodeling.

Synaptic heterogeneity and stimulus-induced modulation of depression in central synapses.

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Hunter, J D; Milton, J G

2001-08-01

Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many forms of plasticity operating over a range of time scales. We develop an optimization method that allows rapid characterization of synapses with multiple time scales of facilitation and depression. Investigation of paired neurons that are postsynaptic to the same identified interneuron in the buccal ganglion of Aplysia reveals that the responses of the two neurons differ in the magnitude of synaptic depression. Also, for single neurons, prolonged stimulation of the presynaptic neuron causes stimulus-induced increases in the early phase of synaptic depression. These observations can be described by a model that incorporates two availability factors, e.g., depletable vesicle pools or desensitizing receptor populations, with different time courses of recovery, and a single facilitation component. This model accurately predicts the responses to novel stimuli. The source of synaptic heterogeneity is identified with variations in the relative sizes of the two availability factors, and the stimulus-induced decrement in the early synaptic response is explained by a slowing of the recovery rate of one of the availability factors. The synaptic heterogeneity and stimulus-induced modifications in synaptic depression observed here emphasize that synaptic efficacy depends on both the individual properties of synapses and their past history.

The chemical component of the mixed GF-TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter.

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Allen, Marcus J; Murphey, R K

2007-07-01

The largest central synapse in adult Drosophila is a mixed electro-chemical synapse whose gap junctions require the product of the shaking-B (shak-B) gene. Shak-B(2) mutant flies lack gap junctions at this synapse, which is between the giant fibre (GF) and the tergotrochanteral motor neuron (TTMn), but it still exhibits a long latency response upon GF stimulation. We have targeted the expression of the light chain of tetanus toxin to the GF, to block chemical transmission, in shak-B(2) flies. The long latency response in the tergotrochanteral muscle (TTM) was abolished indicating that the chemical component of the synapse mediates this response. Attenuation of GAL4-mediated labelling by a cha-GAL80 transgene, reveals the GF to be cholinergic. We have used a temperature-sensitive allele of the choline acetyltransferase gene (cha(ts2)) to block cholinergic synapses in adult flies and this also abolished the long latency response in shak-B(2) flies. Taken together the data provide evidence that both components of this mixed synapse are functional and that the chemical neurotransmitter between the GF and the TTMn is acetylcholine. Our findings show that the two components of this synapse can be separated to allow further studies into the mechanisms by which mixed synapses are built and function.

Energy-efficient STDP-based learning circuits with memristor synapses

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Wu, Xinyu; Saxena, Vishal; Campbell, Kristy A.

2014-05-01

It is now accepted that the traditional von Neumann architecture, with processor and memory separation, is ill suited to process parallel data streams which a mammalian brain can efficiently handle. Moreover, researchers now envision computing architectures which enable cognitive processing of massive amounts of data by identifying spatio-temporal relationships in real-time and solving complex pattern recognition problems. Memristor cross-point arrays, integrated with standard CMOS technology, are expected to result in massively parallel and low-power Neuromorphic computing architectures. Recently, significant progress has been made in spiking neural networks (SNN) which emulate data processing in the cortical brain. These architectures comprise of a dense network of neurons and the synapses formed between the axons and dendrites. Further, unsupervised or supervised competitive learning schemes are being investigated for global training of the network. In contrast to a software implementation, hardware realization of these networks requires massive circuit overhead for addressing and individually updating network weights. Instead, we employ bio-inspired learning rules such as the spike-timing-dependent plasticity (STDP) to efficiently update the network weights locally. To realize SNNs on a chip, we propose to use densely integrating mixed-signal integrate-andfire neurons (IFNs) and cross-point arrays of memristors in back-end-of-the-line (BEOL) of CMOS chips. Novel IFN circuits have been designed to drive memristive synapses in parallel while maintaining overall power efficiency (<1 pJ/spike/synapse), even at spike rate greater than 10 MHz. We present circuit design details and simulation results of the IFN with memristor synapses, its response to incoming spike trains and STDP learning characterization.

ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions.

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Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Potluri, Srilatha; Fu, Xiu-Qing; Luo, Zhen-Ge; Nagappan, Guhan; Chan, Jia Pei; Hempstead, Barbara; Son, Young-Jin; Lu, Bai

2013-06-12

During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo.

Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

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Smith, Lindsey A; McMahon, Lori L

2018-02-01

Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides

Otanps synapse linear relation multiplier circuit

International Nuclear Information System (INIS)

Chible, H.

2008-01-01

In this paper, a four quadrant VLSI analog multiplier will be proposed, in order to be used in the implementation of the neurons and synapses modules of the artificial neural networks. The main characteristics of this multiplier are the small silicon area and the low power consumption and the high value of the weight input voltage. (author)

Impacts of hybrid synapses on the noise-delayed decay in scale-free neural networks

International Nuclear Information System (INIS)

Yilmaz, Ergin

2014-01-01

Highlights: • We investigate the NDD phenomenon in a hybrid scale-free network. • Electrical synapses are more impressive on the emergence of NDD. • Electrical synapses are more efficient in suppressing of the NDD. • Average degree has two opposite effects on the appearance time of the first spike. - Abstract: We study the phenomenon of noise-delayed decay in a scale-free neural network consisting of excitable FitzHugh–Nagumo neurons. In contrast to earlier works, where only electrical synapses are considered among neurons, we primarily examine the effects of hybrid synapses on the noise-delayed decay in this study. We show that the electrical synaptic coupling is more impressive than the chemical coupling in determining the appearance time of the first-spike and more efficient on the mitigation of the delay time in the detection of a suprathreshold input signal. We obtain that hybrid networks including inhibitory chemical synapses have higher signal detection capabilities than those of including excitatory ones. We also find that average degree exhibits two different effects, which are strengthening and weakening the noise-delayed decay effect depending on the noise intensity

Volterra representation enables modeling of complex synaptic nonlinear dynamics in large-scale simulations.

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Hu, Eric Y; Bouteiller, Jean-Marie C; Song, Dong; Baudry, Michel; Berger, Theodore W

2015-01-01

Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO) synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

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Ohno, Takeo; Hasegawa, Tsuyoshi; Tsuruoka, Tohru; Terabe, Kazuya; Gimzewski, James K.; Aono, Masakazu

2011-08-01

Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs , , , ). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag2S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag2S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag2S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2

DEFF Research Database (Denmark)

Zheng, Sika; Gray, Erin E; Chawla, Geetanjali

2012-01-01

. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus...

Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex

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Toriumi, Kazuya; Mouri, Akihiro; Narusawa, Shiho; Aoyama, Yuki; Ikawa, Natsumi; Lu, Lingling; Nagai, Taku; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

2012-01-01

N-methyl--aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression. PMID:22257896

Glutamatergic Effects of Divalproex in Adolescents with Mania: A Proton Magnetic Resonance Spectroscopy Study

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Strawn, Jeffrey R.; Patel, Nick C.; Chu, Wen-Jang; Lee, Jing-Huei; Adler, Caleb M.; Kim, Mi Jung; Bryan, Holly S.; Alfieri, David C.; Welge, Jeffrey A.; Blom, Thomas J.; Nandagopal, Jayasree J.; Strakowski, Stephen M.; DelBello, Melissa P.

2012-01-01

Objectives: This study used proton magnetic resonance spectroscopy ([superscript 1]H MRS) to evaluate the in vivo effects of extended-release divalproex sodium on the glutamatergic system in adolescents with bipolar disorder, and to identify baseline neurochemical predictors of clinical remission. Method: Adolescents with bipolar disorder who were…

Combined effect of chemical and electrical synapses in Hindmarsh-Rose neural networks on synchronization and the rate of information.

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Baptista, M S; Moukam Kakmeni, F M; Grebogi, C

2010-09-01

In this work we studied the combined action of chemical and electrical synapses in small networks of Hindmarsh-Rose (HR) neurons on the synchronous behavior and on the rate of information produced (per time unit) by the networks. We show that if the chemical synapse is excitatory, the larger the chemical synapse strength used the smaller the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find desynchronous behavior. Otherwise, if the chemical synapse is inhibitory, the larger the chemical synapse strength used the larger the electrical synapse strength needed to achieve complete synchronization, and for moderate synaptic strengths one should expect to find synchronous behaviors. Finally, we show how to calculate semianalytically an upper bound for the rate of information produced per time unit (Kolmogorov-Sinai entropy) in larger networks. As an application, we show that this upper bound is linearly proportional to the number of neurons in a network whose neurons are highly connected.

Differential regulation of polarized synaptic vesicle trafficking and synapse stability in neural circuit rewiring in Caenorhabditis elegans.

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Naina Kurup

2017-06-01

Full Text Available Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement.

Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b1

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Doherty, Melissa; Osborne, Douglas G.; Browning, Diana L.; Parker, David C.; Wetzel, Scott A.

2010-01-01

CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction. PMID:20207996

New players tip the scales in the balance between excitatory and inhibitory synapses

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El-Husseini Alaa

2005-03-01

Full Text Available Abstract Synaptogenesis is a highly controlled process, involving a vast array of players which include cell adhesion molecules, scaffolding and signaling proteins, neurotransmitter receptors and proteins associated with the synaptic vesicle machinery. These molecules cooperate in an intricate manner on both the pre- and postsynaptic sides to orchestrate the precise assembly of neuronal contacts. This is an amazing feat considering that a single neuron receives tens of thousands of synaptic inputs but virtually no mismatch between pre- and postsynaptic components occur in vivo. One crucial aspect of synapse formation is whether a nascent synapse will develop into an excitatory or inhibitory contact. The tight control of a balance between the types of synapses formed regulates the overall neuronal excitability, and is thus critical for normal brain function and plasticity. However, little is known about how this balance is achieved. This review discusses recent findings which provide clues to how neurons may control excitatory and inhibitory synapse formation, with focus on the involvement of the neuroligin family and PSD-95 in this process.

Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

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Melanie A Gainey

Full Text Available Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1 during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

Nanogranular SiO{sub 2} proton gated silicon layer transistor mimicking biological synapses

Energy Technology Data Exchange (ETDEWEB)

Liu, M. J.; Huang, G. S., E-mail: gshuang@fudan.edu.cn, E-mail: pfeng@nju.edu.cn; Guo, Q. L.; Tian, Z. A.; Li, G. J.; Mei, Y. F. [Department of Materials Science, Fudan University, Shanghai 200433 (China); Feng, P., E-mail: gshuang@fudan.edu.cn, E-mail: pfeng@nju.edu.cn; Shao, F.; Wan, Q. [School of Electronic Science and Engineering and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093 (China)

2016-06-20

Silicon on insulator (SOI)-based transistors gated by nanogranular SiO{sub 2} proton conducting electrolytes were fabricated to mimic synapse behaviors. This SOI-based device has both top proton gate and bottom buried oxide gate. Electrical transfer properties of top proton gate show hysteresis curves different from those of bottom gate, and therefore, excitatory post-synaptic current and paired pulse facilitation (PPF) behavior of biological synapses are mimicked. Moreover, we noticed that PPF index can be effectively tuned by the spike interval applied on the top proton gate. Synaptic behaviors and functions, like short-term memory, and its properties are also experimentally demonstrated in our device. Such SOI-based electronic synapses are promising for building neuromorphic systems.

Neurotrophin-3 Regulates Synapse Development by Modulating TrkC-PTPσ Synaptic Adhesion and Intracellular Signaling Pathways.

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Han, Kyung Ah; Woo, Doyeon; Kim, Seungjoon; Choii, Gayoung; Jeon, Sangmin; Won, Seoung Youn; Kim, Ho Min; Heo, Won Do; Um, Ji Won; Ko, Jaewon

2016-04-27

Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes. In this study, we present several lines of experimental evidences to support the conclusion that

Long-term potentiation expands information content of hippocampal dentate gyrus synapses.

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Bromer, Cailey; Bartol, Thomas M; Bowden, Jared B; Hubbard, Dusten D; Hanka, Dakota C; Gonzalez, Paola V; Kuwajima, Masaaki; Mendenhall, John M; Parker, Patrick H; Abraham, Wickliffe C; Sejnowski, Terrence J; Harris, Kristen M

2018-03-06

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

Hoisting the Sails, Shining the Bright Pearl——Interviewing LiQingPing, Vice Chairman of the Board of International Pearl Jadeite Jewelry Investment Company, General Manager & CEO of Ming Qin Jewelry Group

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

@@ Li Qingping was born in Wuning County, Jiangxi Province, in 1954. Now, he is Vice Chairman of the Board of International Pearl, Jadeite and Jewelry Investment Company, General Manager & CEO of Ming Qin Jewelry Group.

The sticky synapse

DEFF Research Database (Denmark)

Owczarek, Sylwia Elzbieta; Kristiansen, Lars Villiam; Hortsch, Michael

NCAM-type proteins modulate multiple neuronal functions, including the outgrowth and guidance of neurites, the formation, maturation, and plasticity of synapses, and the induction of both long-term potentiation and long-term depression. The ectodomains of NCAM proteins have a basic structure...... mediate cell-cell adhesion through homophilic interactions and bind to growth factors, growth factor receptors, glutamate receptors, other CAMs, and components of the extracellular matrix. Intracellularly, NCAM-type proteins interact with various cytoskeletal proteins and regulators of intracellular...... signal transduction. A central feature of the synaptic function of NCAM proteins is the regulation of their extracellular interactions by adhesion-modulating glycoepitopes, their removal from the cell surface by endocytosis, and the elimination of their adhesion-mediating interactions by the proteolytic...

Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

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Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

2009-01-01

Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

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Grzegorz eWiera

2015-11-01

Full Text Available Brain is continuously altered in response to experience and environmental changes. One of the underlying mechanisms is synaptic plasticity, which is manifested by modification of synapse structure and function. It is becoming clear that regulated extracellular proteolysis plays a pivotal role in the structural and functional remodeling of synapses during brain development, learning and memory formation. Clearly, plasticity mechanisms may substantially differ between projections. Mossy fiber synapses onto CA3 pyramidal cells display several unique functional features, including pronounced short-term facilitation, a presynaptically expressed LTP that is independent of NMDAR activation, and NMDA-dependent metaplasticity. Moreover, structural plasticity at mossy fiber synapses ranges from the reorganization of projection topology after hippocampus-dependent learning, through intrinsically different dynamic properties of synaptic boutons to pre- and postsynaptic structural changes accompanying LTP induction. Although concomitant functional and structural plasticity in this pathway strongly suggests a role of extracellular proteolysis, its impact only starts to be investigated in this projection. In the present report, we review the role of extracellular proteolysis in various aspects of synaptic plasticity in hippocampal mossy fiber synapses. A growing body of evidence demonstrates that among perisynaptic proteases, tPA/plasmin system, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 and metalloproteinases play a crucial role in shaping plastic changes in this projection. We discuss recent advances and emerging hypotheses on the roles of proteases in mechanisms underlying mossy fiber target specific synaptic plasticity and memory formation.

Astrocyte lipid metabolism is critical for synapse development and function in vivo.

Science.gov (United States)

van Deijk, Anne-Lieke F; Camargo, Nutabi; Timmerman, Jaap; Heistek, Tim; Brouwers, Jos F; Mogavero, Floriana; Mansvelder, Huibert D; Smit, August B; Verheijen, Mark H G

2017-04-01

The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682. © 2017 Wiley Periodicals, Inc.

Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

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Anne-Kathrin Theis

2018-04-01

Full Text Available The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs. For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition123

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Koizumi, Hidehiko; Mosher, Bryan; Tariq, Mohammad F.; Zhang, Ruli

2016-01-01

Abstract The rhythm of breathing in mammals, originating within the brainstem pre-Bötzinger complex (pre-BötC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BötC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BötC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BötC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch-mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre-BötC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property. PMID:27275007

Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers.

Science.gov (United States)

Yuzaki, Michisuke

2010-07-01

Several C1q family members, especially the Cbln and C1q-like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)-Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF-Purkinje cell synaptogenesis in vitro and in vivo. Antigen-unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer. © The Author (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

International Nuclear Information System (INIS)

Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

1983-01-01

Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. [ 125 I]alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic

alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

International Nuclear Information System (INIS)

Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

1983-01-01

Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. [ 125 I]alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic

Alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

Energy Technology Data Exchange (ETDEWEB)

Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

1983-02-01

Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. (/sup 125/I)alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic.

alpha-Bungarotoxin labeling and acetylcholinesterase localization at the Mauthner fiber giant synapse in the hatchetfish

Energy Technology Data Exchange (ETDEWEB)

Day, J.W.; Hall, D.H.; Hall, L.M.; Bennett, M.V.

1983-02-01

Autoradiographic and histochemical techniques have been used to characterize further the pharmacology of transmission at the Mauthner fiber giant synapse of the South American hatchetfish. (/sup 125/I)alpha-Bungarotoxin was applied to hatchetfish medullae and a standard autoradiographic procedure was carried out on 3- to 4-microns sections of glutaraldehyde-fixed tissue. All Mauthner fiber giant synapses, as identified by light microscopic criteria, had closely associated silver grains. Labeling was blocked by d-tubocurarine. Glutaraldehyde-fixed slices of hatchetfish medulla were stained histochemically for acetylcholinesterase; all giant synapses that could be identified in the light microscope showed heavy deposits of reaction product. Staining was blocked by diisopropyl-fluorophosphate, which inhibits both pseudocholinesterase and acetylcholinesterase, but was not blocked by tetraisopropylpyrophosphoramide, a specific pseudocholinesterase inhibitor. This evidence strongly supports the suggestion that the Mauthner fiber giant synapse is nicotinic cholinergic.

Emerging roles of the neurotrophin receptor TrkC in synapse organization.

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Naito, Yusuke; Lee, Alfred Kihoon; Takahashi, Hideto

2017-03-01

Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ). TrkC-PTPσ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPσ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPσ interaction, thus facilitating synapse induction at the pre-synaptic side and increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A crystal structure study has revealed the detailed structure of the TrkC-PTPσ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPσ. Thus, there is strong evidence supporting a role for the TrkC-PTPσ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPσ complex may be the underlying cause of certain psychiatric disorders caused by mutations in the gene encoding TrkC (NTRK3), supporting its role in cognitive functions. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage

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Ewan West

2015-06-01

Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ and the loss of synapses. Aggregation of the cellular prion protein (PrPC by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound “natural Aβ”, sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2 and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson’s disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

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Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

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Dávid Csabai

2018-01-01

Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.

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Tiwari, Vivek; Veeraiah, Pandichelvam; Subramaniam, Vaidyanathan; Patel, Anant Bahadur

2014-03-01

This study investigates the effects of ethanol on neuronal and astroglial metabolism using (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of [1,6-(13)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady-state [2-(13)C]acetate experiment and used as constraints during the metabolic model fitting. (1)H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2-(13)C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using (1)H and (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of (13)C-labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. © 2013 International Society for Neurochemistry.

Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives

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Mauro Pettorruso

2014-01-01

Full Text Available Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.

SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

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Lucas Matt

2018-02-01

Full Text Available Altering AMPA receptor (AMPAR content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1 encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1 modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP, while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.

Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

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Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

2015-01-01

Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

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Lizen, Benoit; Moens, Charlotte; Mouheiche, Jinane; Sacré, Thomas; Ahn, Marie-Thérèse; Jeannotte, Lucie; Salti, Ahmad; Gofflot, Françoise

2017-01-01

Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5 transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown. As a first approach to tackle this question, we aimed at determining the molecular programs downstream of the HOXA5 transcription factor in the context of the postnatal brainstem. A comparative transcriptomic analysis was performed in combination with gene expression localization, using a conditional postnatal Hoxa5 loss-of-function mouse model. After inactivation of Hoxa5 at postnatal days (P)1–P4, we established the transcriptome of the brainstem from P21 Hoxa5 conditional mutants using RNA-Seq analysis. One major finding was the downregulation of several genes associated with synaptic function in Hoxa5 mutant specimens including different actors involved in glutamatergic synapse, calcium signaling pathway, and GABAergic synapse. Data were confirmed and extended by reverse transcription quantitative polymerase chain reaction analysis, and the expression of several HOXA5 candidate targets was shown to co-localize with Hoxa5 transcripts in precerebellar nuclei. Together, these new results revealed that HOXA5, through the regulation of key actors of the glutamatergic/GABAergic synapses and calcium signaling, might be involved in synaptogenesis, synaptic transmission, and synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal brainstem. PMID:29187810

Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

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Benoit Lizen

2017-11-01

Full Text Available Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5 transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown. As a first approach to tackle this question, we aimed at determining the molecular programs downstream of the HOXA5 transcription factor in the context of the postnatal brainstem. A comparative transcriptomic analysis was performed in combination with gene expression localization, using a conditional postnatal Hoxa5 loss-of-function mouse model. After inactivation of Hoxa5 at postnatal days (P1–P4, we established the transcriptome of the brainstem from P21 Hoxa5 conditional mutants using RNA-Seq analysis. One major finding was the downregulation of several genes associated with synaptic function in Hoxa5 mutant specimens including different actors involved in glutamatergic synapse, calcium signaling pathway, and GABAergic synapse. Data were confirmed and extended by reverse transcription quantitative polymerase chain reaction analysis, and the expression of several HOXA5 candidate targets was shown to co-localize with Hoxa5 transcripts in precerebellar nuclei. Together, these new results revealed that HOXA5, through the regulation of key actors of the glutamatergic/GABAergic synapses and calcium signaling, might be involved in synaptogenesis, synaptic transmission, and synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal brainstem.

Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum.

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Rancillac, Armelle; Crépel, Francis

2004-02-01

Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long-term changes in synaptic efficacy. In the present study, we show that long-term potentiation (LTP) and long-term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre- and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF-SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF-PC synapses for presynaptic LTP induced in the same conditions. Thus, long-term changes in synaptic efficacy can be accomplished by PF-SCs synapses as well as by PF-PC synapses, suggesting that both types of plasticity might co-operate during cerebellar motor learning.

Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

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Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

2017-07-01

Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

Fine structure of synapses on dendritic spines

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Michael eFrotscher

2014-09-01

Full Text Available Camillo Golgi’s Reazione Nera led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF, which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin, an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as

Emergent Synapse Organizers: LAR-RPTPs and Their Companions.

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Han, K A; Jeon, S; Um, J W; Ko, J

2016-01-01

Leukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) have emerged as key players that organize various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. Recent research has highlighted the roles of LAR-RPTPs at neuronal synapses in mediating distinct synaptic adhesion pathways through interactions with a host of extracellular ligands and in governing a variety of intracellular signaling cascades through binding to various scaffolds and signaling proteins. In this chapter, we review and update current research progress on the extracellular ligands of LAR-RPTPs, regulation of their extracellular interactions by alternative splicing and heparan sulfates, and their intracellular signaling machineries. In particular, we review structural insights on complexes of LAR-RPTPs with their various ligands. These studies lend support to general molecular mechanisms underlying LAR-RPTP-mediated synaptic adhesion and signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanisms of input and output synaptic specificity: finding partners, building synapses, and fine-tuning communication.

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Rawson, Randi L; Martin, E Anne; Williams, Megan E

2017-08-01

For most neurons to function properly, they need to develop synaptic specificity. This requires finding specific partner neurons, building the correct types of synapses, and fine-tuning these synapses in response to neural activity. Synaptic specificity is common at both a neuron's input and output synapses, whereby unique synapses are built depending on the partnering neuron. Neuroscientists have long appreciated the remarkable specificity of neural circuits but identifying molecular mechanisms mediating synaptic specificity has only recently accelerated. Here, we focus on recent progress in understanding input and output synaptic specificity in the mammalian brain. We review newly identified circuit examples for both and the latest research identifying molecular mediators including Kirrel3, FGFs, and DGLα. Lastly, we expect the pace of research on input and output specificity to continue to accelerate with the advent of new technologies in genomics, microscopy, and proteomics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mitochondria and Neurotransmission: Evacuating the Synapse

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Hollenbeck, Peter J.

2005-01-01

An abundance of mitochondria has been the hallmark of synapses since their first ultrastructural description 50 years ago. Mitochondria have been shown to be essential for synaptic form and function in many systems, but until recently it has not been clear exactly what role(s) they play in neurotransmission. Now, evidence from the nervous system of Drosophila identifies the specific subcellular events that are most dependent upon nearby mitochondria.

Synapse-centric mapping of cortical models to the SpiNNaker neuromorphic architecture

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James Courtney Knight

2016-09-01

Full Text Available While the adult human brain has approximately 8.8x10^10 neurons, this number is dwarfed by its 1x10^15 synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously.

Power-law forgetting in synapses with metaplasticity

International Nuclear Information System (INIS)

Mehta, A; Luck, J M

2011-01-01

The idea of using metaplastic synapses to incorporate the separate storage of long- and short-term memories via an array of hidden states was put forward in the cascade model of Fusi et al. In this paper, we devise and investigate two models of a metaplastic synapse based on these general principles. The main difference between the two models lies in their available mechanisms of decay, when a contrarian event occurs after the build-up of a long-term memory. In one case, this leads to the conversion of the long-term memory to a short-term memory of the opposite kind, while in the other, a long-term memory of the opposite kind may be generated as a result. Appropriately enough, the response of both models to short-term events is not affected by this difference in architecture. On the contrary, the transient response of both models, after long-term memories have been created by the passage of sustained signals, is rather different. The asymptotic behaviour of both models is, however, characterised by power-law forgetting with the same universal exponent

Cadmium action in synapses in the brain

International Nuclear Information System (INIS)

Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto

2001-01-01

Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of 109 CdCl 2 into the amygdala of rats, 109 Cd release into the extracellular space was facilitated by stimulation with high K + , suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 μM CdCl 2 . The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and γ-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures

DEFF Research Database (Denmark)

Suñol, C; Babot, Z; Cristòfol, R

2010-01-01

Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons......3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule......M concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1...

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress.

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Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

2014-07-01

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress

Science.gov (United States)

Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

2014-01-01

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress. PMID:24589888

Tlx3 promotes glutamatergic neuronal subtype specification through direct interactions with the chromatin modifier CBP.

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Atsushi Shimomura

Full Text Available Nervous system development relies on the generation of precise numbers of excitatory and inhibitory neurons. The homeodomain transcription factor, T-cell leukemia 3 (Tlx3, functions as the master neuronal fate regulator by instructively promoting the specification of glutamatergic excitatory neurons and suppressing the specification of gamma-aminobutyric acid (GABAergic neurons. However, how Tlx3 promotes glutamatergic neuronal subtype specification is poorly understood. In this study, we found that Tlx3 directly interacts with the epigenetic co-activator cyclic adenosine monophosphate (cAMP-response element-binding protein (CREB-binding protein (CBP and that the Tlx3 homeodomain is essential for this interaction. The interaction between Tlx3 and CBP was enhanced by the three amino acid loop extension (TALE-class homeodomain transcription factor, pre-B-cell leukemia transcription factor 3 (Pbx3. Using mouse embryonic stem (ES cells stably expressing Tlx3, we found that the interaction between Tlx3 and CBP became detectable only after these Tlx3-expressing ES cells were committed to a neural lineage, which coincided with increased Pbx3 expression during neural differentiation from ES cells. Forced expression of mutated Tlx3 lacking the homeodomain in ES cells undergoing neural differentiation resulted in significantly reduced expression of glutamatergic neuronal subtype markers, but had little effect on the expression on pan neural markers. Collectively, our results strongly suggest that functional interplay between Tlx3 and CBP plays a critical role in neuronal subtype specification, providing novel insights into the epigenetic regulatory mechanism that modulates the transcriptional efficacy of a selective set of neuronal subtype-specific genes during differentiation.

Unsupervised learning by spike timing dependent plasticity in phase change memory (PCM synapses

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Stefano eAmbrogio

2016-03-01

Full Text Available We present a novel one-transistor/one-resistor (1T1R synapse for neuromorphic networks, based on phase change memory (PCM technology. The synapse is capable of spike-timing dependent plasticity (STDP, where gradual potentiation relies on set transition, namely crystallization, in the PCM, while depression is achieved via reset or amorphization of a chalcogenide active volume. STDP characteristics are demonstrated by experiments under variable initial conditions and number of pulses. Finally, we support the applicability of the 1T1R synapse for learning and recognition of visual patterns by simulations of fully connected neuromorphic networks with 2 or 3 layers with high recognition efficiency. The proposed scheme provides a feasible low-power solution for on-line unsupervised machine learning in smart reconfigurable sensors.

Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses

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Haowen Liu

2018-02-01

Full Text Available The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release. Notably, however, Ca2+-independent spontaneous release was observed at GABAergic but not cholinergic synapses. Functional screening led to the identification of hypomorphic unc-64/Syntaxin-1A and snb-1/VAMP2 mutants in which mEPSCs are severely impaired, whereas mIPSCs remain unaltered, indicating differential regulation of these currents at cholinergic and GABAergic synapses. Moreover, Ca2+-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca2+-dependent and Ca2+-independent spontaneous release.

Impact of delays on the synchronization transitions of modular neuronal networks with hybrid synapses

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Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok

2013-09-01

The combined effects of the information transmission delay and the ratio of the electrical and chemical synapses on the synchronization transitions in the hybrid modular neuronal network are investigated in this paper. Numerical results show that the synchronization of neuron activities can be either promoted or destroyed as the information transmission delay increases, irrespective of the probability of electrical synapses in the hybrid-synaptic network. Interestingly, when the number of the electrical synapses exceeds a certain level, further increasing its proportion can obviously enhance the spatiotemporal synchronization transitions. Moreover, the coupling strength has a significant effect on the synchronization transition. The dominated type of the synapse always has a more profound effect on the emergency of the synchronous behaviors. Furthermore, the results of the modular neuronal network structures demonstrate that excessive partitioning of the modular network may result in the dramatic detriment of neuronal synchronization. Considering that information transmission delays are inevitable in intra- and inter-neuronal networks communication, the obtained results may have important implications for the exploration of the synchronization mechanism underlying several neural system diseases such as Parkinson's Disease.

Blocking p75 (NTR) receptors alters polyinnervationz of neuromuscular synapses during development.

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Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2011-09-01

High-resolution immunohistochemistry shows that the receptor protein p75(NTR) is present in the nerve terminal, muscle cell, and glial Schwann cell at the neuromuscular junction (NMJ) of postnatal rats (P4-P6) during the synapse elimination period. Blocking the receptor with the antibody anti-p75-192-IgG (1-5 μg/ml, 1 hr) results in reduced endplate potentials (EPPs) in mono- and polyinnervated synapses ex vivo, but the mean number of functional inputs per NMJ does not change for as long as 3 hr. Incubation with exogenous brain-derived neurotrophic factor (BDNF) for 1 hr (50 nM) resulted in a significant increase in the size of the EPPs in all nerve terminals, and preincubation with anti-p75-192-IgG prevented this potentiation. Long exposure (24 hr) in vivo of the NMJs to the antibody anti-p75-192-IgG (1-2 μg/ml) results in a delay of postnatal synapse elimination and even some regrowth of previously withdrawn axons, but also in some acceleration of the morphologic maturation of the postsynaptic nicotinic acetylcholine receptor (nAChR) clusters. The results indicate that p75(NTR) is involved in both ACh release and axonal retraction during postnatal axonal competition and synapse elimination. Copyright © 2011 Wiley-Liss, Inc.

Rola nasion szałwii hiszpańskiej (chia w żywieniu pacjentów geriatrycznych = The role of chia seeds in nutrition in geriatric patients

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Karina Nowak

2016-03-01

               Geriatric patients are a special group of patients, due to the fact that the body of older people there are many changes associated with aging of the body. Deteriorating performance of many systems including the gastrointestinal tract, and respiratory changes occur in the vessels. Changes in the motility of the esophagus called esophageal senile are the result of diseases that occur in this age group. This reduces the acidity of the gastric juice which is the cause of atrophic mucosa and misuse of proton pump inhibitors. This leads also to a reduction in the number of hepatocytes and thereby reduce the weight of the liver. Changes in the urinary system include reduced ability to concentrate and dilute urine and pH adjustment [1]. Older people often suffer from hypertension, atherosclerosis and other cardiovascular diseases. Products, which are the source of many vitamins, minerals or desirable ingredients in the diet of seniors can include chia seeds. Small grains, rich in protein and fatty acids omega-3 and omega-6, containing 100g more calcium than milk can become an important element in the diet of older people. Included in these alpha-linolenic acid (ALA may lower blood pressure in people with untreated hypertension, supports the work of the brain, improves memory and concentration and has protective effects on the cardiovascular system. GISSI-Prevention Study showed that omega-3 may reduce the risk of sudden death, total mortality and cardiovascular disease in patients after recent myocardial infarction [2

Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

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Qian-Kun Yang

2013-01-01

Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

Maternal dietary loads of alpha-tocopherol increase synapse density and glial synaptic coverage in the hippocampus of adult offspring

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S. Salucci

2014-05-01

Full Text Available An increased intake of the antioxidant α-Tocopherol (vitamin E is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Glia-synapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses was increased. These findings indicate that gestational and neonatal exposure to supranutritional tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant glia-synapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning.

On the Universality and Non-Universality of Spiking Neural P Systems With Rules on Synapses.

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Song, Tao; Xu, Jinbang; Pan, Linqiang

2015-12-01

Spiking neural P systems with rules on synapses are a new variant of spiking neural P systems. In the systems, the neuron contains only spikes, while the spiking/forgetting rules are moved on the synapses. It was obtained that such system with 30 neurons (using extended spiking rules) or with 39 neurons (using standard spiking rules) is Turing universal. In this work, this number is improved to 6. Specifically, we construct a Turing universal spiking neural P system with rules on synapses having 6 neurons, which can generate any set of Turing computable natural numbers. As well, it is obtained that spiking neural P system with rules on synapses having less than two neurons are not Turing universal: i) such systems having one neuron can characterize the family of finite sets of natural numbers; ii) the family of sets of numbers generated by the systems having two neurons is included in the family of semi-linear sets of natural numbers.

Specification of spatial identities of cerebellar neuron progenitors by ptf1a and atoh1 for proper production of GABAergic and glutamatergic neurons.

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Yamada, Mayumi; Seto, Yusuke; Taya, Shinichiro; Owa, Tomoo; Inoue, Yukiko U; Inoue, Takayoshi; Kawaguchi, Yoshiya; Nabeshima, Yo-Ichi; Hoshino, Mikio

2014-04-02

In the cerebellum, the bHLH transcription factors Ptf1a and Atoh1 are expressed in distinct neuroepithelial regions, the ventricular zone (VZ) and the rhombic lip (RL), and are required for producing GABAergic and glutamatergic neurons, respectively. However, it is unclear whether Ptf1a or Atoh1 is sufficient for specifying GABAergic or glutamatergic neuronal fates. To test this, we generated two novel knock-in mouse lines, Ptf1a(Atoh1) and Atoh1(Ptf1a), that are designed to express Atoh1 and Ptf1a ectopically in the VZ and RL, respectively. In Ptf1a(Atoh1) embryos, ectopically Atoh1-expressing VZ cells produced glutamatergic neurons, including granule cells and deep cerebellar nuclei neurons. Correspondingly, in Atoh1(Ptf1a) animals, ectopically Ptf1a-expressing RL cells produced GABAergic populations, such as Purkinje cells and GABAergic interneurons. Consistent results were also obtained from in utero electroporation of Ptf1a or Atoh1 into embryonic cerebella, suggesting that Ptf1a and Atoh1 are essential and sufficient for GABAergic versus glutamatergic specification in the neuroepithelium. Furthermore, birthdating analyses with BrdU in the knock-in mice or with electroporation studies showed that ectopically produced fate-changed neuronal types were generated at temporal schedules closely simulating those of the wild-type RL and VZ, suggesting that the VZ and RL share common temporal information. Observations of knock-in brains as well as electroporated brains revealed that Ptf1a and Atoh1 mutually negatively regulate their expression, probably contributing to formation of non-overlapping neuroepithelial domains. These findings suggest that Ptf1a and Atoh1 specify spatial identities of cerebellar neuron progenitors in the neuroepithelium, leading to appropriate production of GABAergic and glutamatergic neurons, respectively.

Optimal recall from bounded metaplastic synapses: predicting functional adaptations in hippocampal area CA3.

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Cristina Savin

2014-02-01

Full Text Available A venerable history of classical work on autoassociative memory has significantly shaped our understanding of several features of the hippocampus, and most prominently of its CA3 area, in relation to memory storage and retrieval. However, existing theories of hippocampal memory processing ignore a key biological constraint affecting memory storage in neural circuits: the bounded dynamical range of synapses. Recent treatments based on the notion of metaplasticity provide a powerful model for individual bounded synapses; however, their implications for the ability of the hippocampus to retrieve memories well and the dynamics of neurons associated with that retrieval are both unknown. Here, we develop a theoretical framework for memory storage and recall with bounded synapses. We formulate the recall of a previously stored pattern from a noisy recall cue and limited-capacity (and therefore lossy synapses as a probabilistic inference problem, and derive neural dynamics that implement approximate inference algorithms to solve this problem efficiently. In particular, for binary synapses with metaplastic states, we demonstrate for the first time that memories can be efficiently read out with biologically plausible network dynamics that are completely constrained by the synaptic plasticity rule, and the statistics of the stored patterns and of the recall cue. Our theory organises into a coherent framework a wide range of existing data about the regulation of excitability, feedback inhibition, and network oscillations in area CA3, and makes novel and directly testable predictions that can guide future experiments.

Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity

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Hongyu Sun

2018-05-01

Full Text Available Heightened neural excitability in infancy and childhood results in increased susceptibility to seizures. Such early-life seizures are associated with language deficits and autism that can result from aberrant development of the auditory cortex. Here, we show that early-life seizures disrupt a critical period (CP for tonotopic map plasticity in primary auditory cortex (A1. We show that this CP is characterized by a prevalence of “silent,” NMDA-receptor (NMDAR-only, glutamate receptor synapses in auditory cortex that become “unsilenced” due to activity-dependent AMPA receptor (AMPAR insertion. Induction of seizures prior to this CP occludes tonotopic map plasticity by prematurely unsilencing NMDAR-only synapses. Further, brief treatment with the AMPAR antagonist NBQX following seizures, prior to the CP, prevents synapse unsilencing and permits subsequent A1 plasticity. These findings reveal that early-life seizures modify CP regulators and suggest that therapeutic targets for early post-seizure treatment can rescue CP plasticity.

Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

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Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

2008-01-01

Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

Natural killer cell signal integration balances synapse symmetry and migration.

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Fiona J Culley

2009-07-01

Full Text Available Natural killer (NK cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a "stop" signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory "kinapses" are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.

Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

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Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi

2016-01-01

Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2′-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring. PMID:26105135

Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model.

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Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara

2017-07-12

Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by A�

Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2

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Elodie De Bruyckere

2018-04-01

Full Text Available Structural and functional plasticity of synapses are critical neuronal mechanisms underlying learning and memory. While activity-dependent regulation of synaptic strength has been extensively studied, much less is known about the transcriptional control of synapse maintenance and plasticity. Hippocampal mossy fiber (MF synapses connect dentate granule cells to CA3 pyramidal neurons and are important for spatial memory formation and consolidation. The transcription factor Bcl11b/Ctip2 is expressed in dentate granule cells and required for postnatal hippocampal development. Ablation of Bcl11b/Ctip2 in the adult hippocampus results in impaired adult neurogenesis and spatial memory. The molecular mechanisms underlying the behavioral impairment remained unclear. Here we show that selective deletion of Bcl11b/Ctip2 in the adult mouse hippocampus leads to a rapid loss of excitatory synapses in CA3 as well as reduced ultrastructural complexity of remaining mossy fiber boutons (MFBs. Moreover, a dramatic decline of long-term potentiation (LTP of the dentate gyrus-CA3 (DG-CA3 projection is caused by adult loss of Bcl11b/Ctip2. Differential transcriptomics revealed the deregulation of genes associated with synaptic transmission in mutants. Together, our data suggest Bcl11b/Ctip2 to regulate maintenance and function of MF synapses in the adult hippocampus.

Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.

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Araque, A; Ferreira, W; Lucas, S; Buño, W

1992-01-31

The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex.

Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain.

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Tiwari, Vivek; Ambadipudi, Susmitha; Patel, Anant B

2013-10-01

The (13)C nuclear magnetic resonance (NMR) studies together with the infusion of (13)C-labeled substrates in rats and humans have provided important insight into brain energy metabolism. In the present study, we have extended a three-compartment metabolic model in mouse to investigate glutamatergic and GABAergic tricarboxylic acid (TCA) cycle and neurotransmitter cycle fluxes across different regions of the brain. The (13)C turnover of amino acids from [1,6-(13)C2]glucose was monitored ex vivo using (1)H-[(13)C]-NMR spectroscopy. The astroglial glutamate pool size, one of the important parameters of the model, was estimated by a short infusion of [2-(13)C]acetate. The ratio Vcyc/VTCA was calculated from the steady-state acetate experiment. The (13)C turnover curves of [4-(13)C]/[3-(13)C]glutamate, [4-(13)C]glutamine, [2-(13)C]/[3-(13)C]GABA, and [3-(13)C]aspartate from [1,6-(13)C2]glucose were analyzed using a three-compartment metabolic model to estimate the rates of the TCA cycle and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The glutamatergic TCA cycle rate was found to be highest in the cerebral cortex (0.91 ± 0.05 μmol/g per minute) and least in the hippocampal region (0.64 ± 0.07 μmol/g per minute) of the mouse brain. In contrast, the GABAergic TCA cycle flux was found to be highest in the thalamus-hypothalamus (0.28 ± 0.01 μmol/g per minute) and least in the cerebral cortex (0.24 ± 0.02 μmol/g per minute). These findings indicate that the energetics of excitatory and inhibitory function is distinct across the mouse brain.

Cadmium action in synapses in the brain

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Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

2001-05-01

Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

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2012-01-01

Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners. PMID:22852823

Hebbian Plasticity Guides Maturation of Glutamate Receptor Fields In Vivo

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Dmitrij Ljaschenko

2013-05-01

Full Text Available Synaptic plasticity shapes the development of functional neural circuits and provides a basis for cellular models of learning and memory. Hebbian plasticity describes an activity-dependent change in synaptic strength that is input-specific and depends on correlated pre- and postsynaptic activity. Although it is recognized that synaptic activity and synapse development are intimately linked, our mechanistic understanding of the coupling is far from complete. Using Channelrhodopsin-2 to evoke activity in vivo, we investigated synaptic plasticity at the glutamatergic Drosophila neuromuscular junction. Remarkably, correlated pre- and postsynaptic stimulation increased postsynaptic sensitivity by promoting synapse-specific recruitment of GluR-IIA-type glutamate receptor subunits into postsynaptic receptor fields. Conversely, GluR-IIA was rapidly removed from synapses whose activity failed to evoke substantial postsynaptic depolarization. Uniting these results with developmental GluR-IIA dynamics provides a comprehensive physiological concept of how Hebbian plasticity guides synaptic maturation and sparse transmitter release controls the stabilization of the molecular composition of individual synapses.

The repetition timing of high frequency afferent stimulation drives the bidirectional plasticity at central synapses in the rat medial vestibular nuclei.

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Scarduzio, M; Panichi, R; Pettorossi, V E; Grassi, S

2012-10-25

In this study we show that high frequency stimulation (HFS, 100Hz) of afferent fibers to the medial vestibular nucleus (MVN) can induce opposite long-term modifications of synaptic responses in the type B neurons depending upon the stimulation pattern. Long burst stimulation (LBS: 2s) and short burst stimulation (SBS: 0.55s) were applied with different burst number (BN) and inter-burst intervals (IBI). It results that both LBS and SBS can induce either N-methyl-d aspartate receptors (NMDARs)-mediated long-term potentiation (LTP) or long-term depression (LTD), depending on temporal organization of repetitive bursts. In particular, the IBI plays a relevant role in guiding the shift from LTP to LTD since by using both LBS and SBS LTP is induced by shorter IBI than LTD. By contrast, the sign of long-term effect does not depend on the mean impulse frequency evaluated within the entire stimulation period. Therefore, the patterns of repetitive vestibular activation with different ratios between periods of increased activity and periods of basal activity may lead to LTP or LTD probably causing different levels of postsynaptic Ca(2+). On the whole, this study demonstrates that glutamatergic vestibular synapse in the MVN can undergo NMDAR-dependent bidirectional plasticity and puts forward a new aspect for understanding the adaptive and compensatory plasticity of the oculomotor responses. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

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Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

The role of neurexins and neuroligins in the formation, maturation, and function of vertebrate synapses.

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Krueger, Dilja D; Tuffy, Liam P; Papadopoulos, Theofilos; Brose, Nils

2012-06-01

Neurexins (NXs) and neuroligins (NLs) are transsynaptically interacting cell adhesion proteins that play a key role in the formation, maturation, activity-dependent validation, and maintenance of synapses. As complex alternative splicing processes in nerve cells generate a large number of NX and NLs variants, it has been proposed that a combinatorial interaction code generated by these variants may determine synapse identity and network connectivity during brain development. The functional importance of NXs and NLs is exemplified by the fact that mutations in NX and NL genes are associated with several neuropsychiatric disorders, most notably with autism. Accordingly, major research efforts have focused on the molecular mechanisms by which NXs and NLs operate at synapses. In this review, we summarize recent progress in this field and discuss emerging topics, such as the role of alternative interaction partners of NXs and NLs in synapse formation and function, and their relevance for synaptic plasticity in the mature brain. The novel findings highlight the fundamental importance of NX-NL interactions in a wide range of synaptic functions. Copyright © 2012 Elsevier Ltd. All rights reserved.

NMDAR-mediated calcium transients elicited by glutamate co-release at developing inhibitory synapses

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Abigail Kalmbach

2010-07-01

Full Text Available Before hearing onset, the topographic organization of the inhibitory sound localization pathway from the medial nucleus of the trapezoid body (MNTB to the lateral superior olive (LSO is refined by means of synaptic silencing and strengthening. During this refinement period MNTB-LSO synapses not only release GABA and glycine but also release glutamate. This co-released glutamate can elicit postsynaptic currents that are predominantly mediated by NMDA receptors (NMDARs. To gain a better understanding of how glutamate contributes to synaptic signaling at developing MNTB-LSO inhibitory synapse, we investigated to what degree and under what conditions NMDARs contribute to postsynaptic calcium responses. Our results demonstrate that MNTB-LSO synapses can elicit compartmentalized calcium responses along aspiny LSO dendrites. These responses are significantly attenuated by the NMDARs antagonist APV. APV, however, has no effect on somatically recorded electrical postsynaptic responses, indicating little, if any, contribution of NMDARs to spike generation. Small NMDAR-mediated calcium responses were also observed under physiological levels of extracellular magnesium concentrations indicating that MNTB-LSO synapses activate magnesium sensitive NMDAR on immature LSO dendrites. In Fura-2 AM loaded neurons, blocking GABAA and glycine receptors decreased NMDAR contribution to somatic calcium responses suggesting that GABA and glycine, perhaps by shunting backpropagating action potentials, decrease the level of NMDAR activation under strong stimulus conditions.

The Taiwanese Perspective in Investigating Korean Confucianism: Lee Ming-huei's Interpretation of Han Wonjin (1682–1750

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Martina GREIF

2014-12-01

Full Text Available Numerous representatives of the contemporary Confucian revival from Taiwan are increasingly demonstrating the fact that the development of Confucian philosophy has to be viewed in a broader cultural context, especially in the context of different East Asian regions. While the development of the Japanese Confucian studies has been elaborated to a great extent during the last decades, studies in Korean Confucianism are still rare. Hence, the present article aims to offer a report on a pioneer contribution in this regard. It introduces Lee Ming-huei’s investigation into the work of one of the most influential Korean Confucians of the Joseon period; on the basis of Huang Chun-chieh’s methodology which exposes the contextualization paradigm, the article explains the main hypotheses and offers a theoretical reflection of the main issues discussed in this research work.

The space where aging acts: focus on the GABAergic synapse.

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Rozycka, Aleksandra; Liguz-Lecznar, Monika

2017-08-01

As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging-related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging-related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging-induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Microorganism and filamentous fungi drive evolution of plant synapses.

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Baluška, František; Mancuso, Stefano

2013-01-01

In the course of plant evolution, there is an obvious trend toward an increased complexity of plant bodies, as well as an increased sophistication of plant behavior and communication. Phenotypic plasticity of plants is based on the polar auxin transport machinery that is directly linked with plant sensory systems impinging on plant behavior and adaptive responses. Similar to the emergence and evolution of eukaryotic cells, evolution of land plants was also shaped and driven by infective and symbiotic microorganisms. These microorganisms are the driving force behind the evolution of plant synapses and other neuronal aspects of higher plants; this is especially pronounced in the root apices. Plant synapses allow synaptic cell-cell communication and coordination in plants, as well as sensory-motor integration in root apices searching for water and mineral nutrition. These neuronal aspects of higher plants are closely linked with their unique ability to adapt to environmental changes.

Simulations of centriole of polarized centrosome as a monopole antenna in immune and viral synapses.

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Dvorak, Josef; Melichar, Bohuslav; Filipova, Alzbeta; Grimova, Jana; Grimova, Nela; Rozsypalova, Aneta; Buka, David; Voboril, Rene; Zapletal, Radek; Buchler, Tomas; Richter, Igor; Buka, David

2018-01-01

The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules. We are extending this prior hypothesis of the endogenous electromagnetic field in the cell postulating that polarized centriole in immune and viral synapse could serve as a monopole antenna. This is an addition to our hypothesis that primary cilium could serve as a monopole antenna. We simulated the distribution of electric field of centriole of polarized centrosome as a monopole antenna in immune and viral synapse. Very weak electromagnetic field of polarized centriole of CD8+ T lymphocyte in IS can contribute to the transport of cytolytic granules into the attacked (cancer) cell. Analogically, very weak electromagnetic field of polarized centriole in viral synapse of infected CD4 cells can aid the transport of viruses (human immunodeficiency virus) to non-infected CD4 cells. We hypothesized that healthy organisms need these monopole antennas. If, during the neoplastic transformation, healthy cells lose monopole antennas in form of primary cilia, the IS aims to replace them by monopole antennas of polarized centrioles in IS to restore homeostasis.

Enhanced Long-Term Microcircuit Plasticity in the Valproic Acid Animal Model of Autism

OpenAIRE

Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad; Rinaldi, Tania; Markram, Kamila; Markram, Henry

2009-01-01

A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (

Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

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Gardell, Jennifer L; Parker, David C

2017-01-01

Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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Tanaka Mika

2013-01-01

Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

A cortical attractor network with Martinotti cells driven by facilitating synapses.

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Pradeep Krishnamurthy

Full Text Available The population of pyramidal cells significantly outnumbers the inhibitory interneurons in the neocortex, while at the same time the diversity of interneuron types is much more pronounced. One acknowledged key role of inhibition is to control the rate and patterning of pyramidal cell firing via negative feedback, but most likely the diversity of inhibitory pathways is matched by a corresponding diversity of functional roles. An important distinguishing feature of cortical interneurons is the variability of the short-term plasticity properties of synapses received from pyramidal cells. The Martinotti cell type has recently come under scrutiny due to the distinctly facilitating nature of the synapses they receive from pyramidal cells. This distinguishes these neurons from basket cells and other inhibitory interneurons typically targeted by depressing synapses. A key aspect of the work reported here has been to pinpoint the role of this variability. We first set out to reproduce quantitatively based on in vitro data the di-synaptic inhibitory microcircuit connecting two pyramidal cells via one or a few Martinotti cells. In a second step, we embedded this microcircuit in a previously developed attractor memory network model of neocortical layers 2/3. This model network demonstrated that basket cells with their characteristic depressing synapses are the first to discharge when the network enters an attractor state and that Martinotti cells respond with a delay, thereby shifting the excitation-inhibition balance and acting to terminate the attractor state. A parameter sensitivity analysis suggested that Martinotti cells might, in fact, play a dominant role in setting the attractor dwell time and thus cortical speed of processing, with cellular adaptation and synaptic depression having a less prominent role than previously thought.

Nasiona szałwii hiszpańskiej (Salvia Hispanica L. jako źródło składników wykazujących dobroczynny wpływ na ludzki organizm = Chia seeds (Salvia hispanica L. as a source of ingredients with beneficial influence on human organism

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Grzegorz Dąbrowski

2015-09-01

  Uniwersytet Warmińsko-Mazurski w Olsztynie Katedra Przetwórstwa i Chemii Surowców Roślinnych Pl. Cieszyński 1, 10-726 Olsztyn e-mail: grzegorz.dabrowski@uwm.edu.pl   Abstrakt Nasiona szałwii hiszpańskiej były jednym z najważniejszych źródeł pożywienia cywilizacji środkowoamerykańskich z czasów przedkolumbijskich. Z żywieniowego punktu widzenia bardzo interesujący jest ich skład chemiczny. Zawierają one duże ilości polienowych kwasów tłuszczowych. Najbardziej wartościowy jest kwas α-linolenowy, który ma między innymi zdolność zapobiegania chorobie wieńcowej i cukrzycy. Obecność kwasów fenolowych, tokoferoli i flawonoidów pomaga zapewnić stabilność oksydacyjną tłuszczu z nasion szałwii. Zawierają one duże ilości frakcji błonnika pokarmowego. Zawartość nierozpuszczalnej frakcji błonnika jest od 4 do 5 razy wyższa niż frakcji nierozpuszczalnej. Stosunek ten jest korzystny i może odgrywać rolę przy obniżaniu poziomu cholesterolu we krwi. Frakcja białkowa nasion szałwii zawiera duże ilości aminokwasów egzogennych i może być źródłem bioaktywnych peptydów. Słowa kluczowe: Salvia hispanica L., polienowe kwasy tłuszczowe, włókno pokarmowe, przeciwutleniacze, białka.   Abstract Chia (Salvia hispanica L. seeds were one of the most important sources of food for Central American civilizations in pre-Columbian times. The chemical composition of chia seeds is very interesting from nutritional point of view. It contains large amounts of polyunsaturated fatty acids. Most valuable is α-linoleic acid that can be helpful in between in coronary heart disease or diabetes prevention. The presence of phenolic acids, tocopherols and flavonoids helps to provide oxidative stability of oil from chia seeds. Chia seeds contain large amounts of dietary fiber. Content of insoluble fraction of dietary fiber is 4-5 times higher than soluble. It is good proportion and it can be helpful in lowering cholesterol content in blood

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

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Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

2011-01-01

Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

Reciprocal synapses between outer hair cells and their afferent terminals: evidence for a local neural network in the mammalian cochlea.

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Thiers, Fabio A; Nadol, Joseph B; Liberman, M Charles

2008-12-01

Cochlear outer hair cells (OHCs) serve both as sensory receptors and biological motors. Their sensory function is poorly understood because their afferent innervation, the type-II spiral ganglion cell, has small unmyelinated axons and constitutes only 5% of the cochlear nerve. Reciprocal synapses between OHCs and their type-II terminals, consisting of paired afferent and efferent specialization, have been described in the primate cochlea. Here, we use serial and semi-serial-section transmission electron microscopy to quantify the nature and number of synaptic interactions in the OHC area of adult cats. Reciprocal synapses were found in all OHC rows and all cochlear frequency regions. They were more common among third-row OHCs and in the apical half of the cochlea, where 86% of synapses were reciprocal. The relative frequency of reciprocal synapses was unchanged following surgical transection of the olivocochlear bundle in one cat, confirming that reciprocal synapses were not formed by efferent fibers. In the normal ear, axo-dendritic synapses between olivocochlear terminals and type-II terminals and/or dendrites were as common as synapses between olivocochlear terminals and OHCs, especially in the first row, where, on average, almost 30 such synapses were seen in the region under a single OHC. The results suggest that a complex local neuronal circuitry in the OHC area, formed by the dendrites of type-II neurons and modulated by the olivocochlear system, may be a fundamental property of the mammalian cochlea, rather than a curiosity of the primate ear. This network may mediate local feedback control of, and bidirectional communication among, OHCs throughout the cochlear spiral.

Visualization by high resolution immunoelectron microscopy of the transient receptor potential vanilloid-1 at inhibitory synapses of the mouse dentate gyrus.

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Miren-Josune Canduela

Full Text Available We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1, a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML. In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (∼60% of total immunoparticles at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.

Label-free visualization of ultrastructural features of artificial synapses via cryo-EM.

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Gopalakrishnan, Gopakumar; Yam, Patricia T; Madwar, Carolin; Bostina, Mihnea; Rouiller, Isabelle; Colman, David R; Lennox, R Bruce

2011-12-21

The ultrastructural details of presynapses formed between artificial substrates of submicrometer silica beads and hippocampal neurons are visualized via cryo-electron microscopy (cryo-EM). The silica beads are derivatized by poly-d-lysine or lipid bilayers. Molecular features known to exist at presynapses are clearly present at these artificial synapses, as visualized by cryo-EM. Key synaptic features such as the membrane contact area at synaptic junctions, the presynaptic bouton containing presynaptic vesicles, as well as microtubular structures can be identified. This is the first report of the direct, label-free observation of ultrastructural details of artificial synapses.

Autaptic effects on synchrony of neurons coupled by electrical synapses

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Kim, Youngtae

2017-07-01

In this paper, we numerically study the effects of a special synapse known as autapse on synchronization of population of Morris-Lecar (ML) neurons coupled by electrical synapses. Several configurations of the ML neuronal populations such as a pair or a ring or a globally coupled network with and without autapses are examined. While most of the papers on the autaptic effects on synchronization have used networks of neurons of same spiking rate, we use the network of neurons of different spiking rates. We find that the optimal autaptic coupling strength and the autaptic time delay enhance synchronization in our neural networks. We use the phase response curve analysis to explain the enhanced synchronization by autapses. Our findings reveal the important relationship between the intraneuronal feedback loop and the interneuronal coupling.

Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease.

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Jackson, Rosemary J; Rudinskiy, Nikita; Herrmann, Abigail G; Croft, Shaun; Kim, JeeSoo Monica; Petrova, Veselina; Ramos-Rodriguez, Juan Jose; Pitstick, Rose; Wegmann, Susanne; Garcia-Alloza, Monica; Carlson, George A; Hyman, Bradley T; Spires-Jones, Tara L

2016-12-01

Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Synapses of the rat end brain in response to flight effects

International Nuclear Information System (INIS)

Antipov, V.V.; Tikhonchuk, V.S.; Ushakov, I.B.; Fedorov, V.P.

1988-01-01

Using electron microscopy, synapses of different structures of the rat end brain related to cognitive and motor acts (sensorimotor cortex, caudate nucleus) as well as memory and behavior (hippocampus) were examined. Rats were exposed to ionizing radiation, superhigh frequency, hypoxia, hyperoxia, vibration and acceleration (applied separately or in combination) which have been traditionally in the focus of space and aviation medicine. Brain internuronal junctions were found to be very sensitive to the above effects, particularly ionizing radiation and hypoxia. Conversely, synapses were shown to be highly resistant to short-term hyperoxia and electromagnetic radiation. When combined effects were used, response of interneuronal junctions depended on the irradiation dose and order of application of radiation and other flight factors

Selective serotonin reuptake inhibitors and the risk of hepatocellular carcinoma in hepatitis B virus-infected patients

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Chang CM

2017-11-01

Full Text Available Chia-Ming Chang,1–3 Ming-Shun Hsieh,1–4 Tsung-Chieh Yang,3,5 Vivian Chia-Rong Hsieh,6 Jen-Huai Chiang,7 Hsien-Hao Huang,1,3 Chorng-Kuang How,1,3 Sung-Yuan Hu,8 David Hung-Tsang Yen1,3 1Department of Emergency Medicine, Taipei Veterans General Hospital, 2Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, 3College of Medicine, National Yang-Ming University, Taipei, 4Department of Emergency Medicine, 5Division of Gastroenterology, Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, 6Department of Health Services Administration, 7Management Office for Health Data, China Medical University, 8Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China Background: This study aimed to investigate the association between the use of selective serotonin reuptake inhibitors (SSRIs and the risk of hepatocellular carcinoma (HCC in patients with chronic hepatitis B virus (HBV infection.Methods: We conducted a population-based cohort study by using claims data from the Taiwan National Health Insurance Research Database (NHIRD. The study cohort comprised 1380 newly diagnosed HBV-infected patients with SSRI use who were frequency matched by age, sex, liver cirrhosis, and index year with HBV-infected patients without SSRI use in the comparison cohort. Each patient case was followed from 2000 to 2012 to identify incident HCC cases. Cox proportional hazards regression was performed to evaluate the association between SSRI use and HCC risk. The further sensitivity analysis used case-control study design. A total of 9070 HCC subjects retrieved from NHIRD, and equal non-HCC subjects were analyzed after matching for age and sex.Results: We identified 9 and 24 HCC cases in the study and comparison cohorts during the follow-up period of 7056 and 6845 person-years, respectively. The incidence rate of HCC was 1.28 and 3

[The innovation of warm disease theory in the Ming Dynasty before Wen yi lun On Pestilence].

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Zhang, Zhi-bin

2008-10-01

Some doctors of the Ming dynasty raised subversive doubts against the traditional viewpoints of "exogenous cold disease is warm-heat" before the emergence of Wen yi lun (On Pestilence), holding that warm-heat disease "is contracted in different seasons instead of being transformed from cold to warm and/or heat". The conception of the separation of warm-heat disease and exogenous cold disease had changed from obscure to clear. As the idea became clear, the recognition on the new affection of warm, heat, summer-heat, pestilent pathogen was formed, and the idea that the pathogens of summer-heat and warm entered the human body through the mouth and nostrils was put forward. The six-channel syndrome differentiation of warm disease and the five sweat-resolving methods in pestilence raised by the doctors of this period are the aspects of the differential diagnosis of syndrome and treatment in warm diseases, and deserve to be paid attention to.

Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

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Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

2017-01-01

During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

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Josep Tomàs

2017-05-01

Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss.

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Zhuang, Xiaowen; Sun, Wei; Xu-Friedman, Matthew A

2017-01-11

Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal

Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems

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Arico Maurizo

2011-06-01

Full Text Available Abstract Background Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs, this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK and invariant NKT (iNKT cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. Results NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked' with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. Conclusions These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system direct secretory lysosomes to

Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems.

Science.gov (United States)

Stinchcombe, Jane C; Salio, Mariolina; Cerundolo, Vincenzo; Pende, Daniela; Arico, Maurizo; Griffiths, Gillian M

2011-06-28

Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release. NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse. These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the

GLUT4 Mobilization Supports Energetic Demands of Active Synapses.

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Ashrafi, Ghazaleh; Wu, Zhuhao; Farrell, Ryan J; Ryan, Timothy A

2017-02-08

The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter GLUT4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of GLUT4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of GLUT4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for "exercising" synapses is reminiscent of that occurring in exercising muscle to sustain cellular function and identifies nerve terminals as critical sites of proper metabolic control. Copyright © 2017 Elsevier Inc. All rights reserved.

Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

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Marta Esteves da Silva

2015-11-01

Full Text Available Lateral diffusion in the membrane and endosomal trafficking both contribute to the addition and removal of AMPA receptors (AMPARs at postsynaptic sites. However, the spatial coordination between these mechanisms has remained unclear, because little is known about the dynamics of AMPAR-containing endosomes. In addition, how the positioning of AMPAR-containing endosomes affects synapse organization and functioning has never been directly explored. Here, we used live-cell imaging in hippocampal neuron cultures to show that intracellular AMPARs are transported in Rab11-positive recycling endosomes, which frequently enter dendritic spines and depend on the microtubule and actin cytoskeleton. By using chemically induced dimerization systems to recruit kinesin (KIF1C or myosin (MyosinV/VI motors to Rab11-positive recycling endosomes, we controlled their trafficking and found that induced removal of recycling endosomes from spines decreases surface AMPAR expression and PSD-95 clusters at synapses. Our data suggest a mechanistic link between endosome positioning and postsynaptic structure and composition.

Activity strengths of cortical glutamatergic and GABAergic neurons are correlated with transgenerational inheritance of learning ability.

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Liu, Yulong; Ge, Rongjing; Zhao, Xin; Guo, Rui; Huang, Li; Zhao, Shidi; Guan, Sudong; Lu, Wei; Cui, Shan; Wang, Shirlene; Wang, Jin-Hui

2017-12-22

The capabilities of learning and memory in parents are presumably transmitted to their offsprings, in which genetic codes and epigenetic regulations are thought as molecular bases. As neural plasticity occurs during memory formation as cellular mechanism, we aim to examine the correlation of activity strengths at cortical glutamatergic and GABAergic neurons to the transgenerational inheritance of learning ability. In a mouse model of associative learning, paired whisker and odor stimulations led to odorant-induced whisker motion, whose onset appeared fast (high learning efficiency, HLE) or slow (low learning efficiency, LLE). HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice were cross-mated to have their first generation of offsprings, filials (F1). The onset of odorant-induced whisker motion appeared a sequence of high-to-low efficiency in three groups of F1 mice that were from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Activities related to glutamatergic neurons in barrel cortices appeared a sequence of high-to-low strength in these F1 mice from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Activities related to GABAergic neurons in barrel cortices appeared a sequence of low-to-high strength in these F1 mice from HLE male and female mice, HLE female and LLE male mice as well as HLE male and LLE female mice. Neuronal activity strength was linearly correlated to learning efficiency among three groups. Thus, the coordinated activities at glutamatergic and GABAergic neurons may constitute the cellular basis for the transgenerational inheritance of learning ability.

Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons.

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Gill, Luther C; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

2016-06-01

Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a well-established model of SCI, unilateral spinal hemisection of the C2 segment of the cervical spinal cord (SH), provide novel information regarding the molecular and cellular mechanisms of functional recovery after SCI. Over time post-SH, gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. Conversely, recovery after SH is blunted by quenching endogenous BDNF with the fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by selective inhibition of TrkB kinase activity using a chemical-genetic approach in TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB receptors at phrenic motoneurons is highlighted by the blunting of recovery by siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons and by the enhancement of recovery evident following virally-induced increases in TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling regulates synaptic plasticity in various neuronal systems, including glutamatergic pathways. Glutamatergic neurotransmission constitutes the main inspiratory-related, excitatory drive to motoneurons, and following SH, spontaneous neuroplasticity is associated with increased expression of ionotropic N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity following cervical SCI is reviewed. Copyright © 2015 Elsevier B.V. All rights reserved.

Identity and Friendship in Hsu-Ming Teo´s Behind the Moon (2000

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Catalina Ribas Segura

2015-03-01

Full Text Available In her second novel, Behind the Moon (2000, Hsu-Ming Teo explores the identity construction of three teenage friends and how they defy the notion of the „ideal‟ Australian as a heterosexual, Protestant, white, English-speaking, Australian-born of British ancestry young adult person. Set in the western suburbs of Sydney in the 1990s, the three friends are an example of the multicultural society of the time: Justin Cheong, the son of a Chinese-Singaporean family who arrived in Australia with the Business Migration Programme; Tien Ho, a refugee girl of Chinese-Vietnamese and Afro-CajunCreole-American ancestry; and Nigel „Gibbo‟ Gibson, the son of an Anglo-Australian father and an English mother. The novel tackles different relations among these characters and their families during their teenage years and especially as young adults. This paper seeks to analyse the evolution of the identities of Justin, Tien and „Gibbo‟ through the notions of belonging, gender construction and sexuality. In order to do so, the main theories applied will be the insights on homosexuality and on masculinities of Maria Pallotta-Chiarolli (1995 and Raewyn W. Connell (1995 and Manuel Castellsʼ (2010 identity construction theory

N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease.

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Wright, Dean J; Gray, Laura J; Finkelstein, David I; Crouch, Peter J; Pow, David; Pang, Terence Y; Li, Shanshan; Smith, Zoe M; Francis, Paul S; Renoir, Thibault; Hannan, Anthony J

2016-07-15

Glutamatergic dysfunction has been implicated in the pathogenesis of depressive disorders and Huntington's disease (HD), in which depression is the most common psychiatric symptom. Synaptic glutamate homeostasis is regulated by cystine-dependent glutamate transporters, including GLT-1 and system x c - In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine-γ-lygase, has recently been shown to be lowered. The aim of the present study was to establish whether cysteine supplementation, using N-acetylcysteine (NAC) could ameliorate glutamate pathology through the cystine-dependent transporters, system x c - and GLT-1. We demonstrate that the R6/1 transgenic mouse model of HD has lower basal levels of cystine, and showed depressive-like behaviors in the forced-swim test. Administration of NAC reversed these behaviors. This effect was blocked by co-administration of the system x c - and GLT-1 inhibitors CPG and DHK, showing that glutamate transporter activity was required for the antidepressant effects of NAC. NAC was also able to specifically increase glutamate in HD mice, in a glutamate transporter-dependent manner. These in vivo changes reflect changes in glutamate transporter protein in HD mice and human HD post-mortem tissue. Furthermore, NAC was able to rescue changes in key glutamate receptor proteins related to excitotoxicity in HD, including NMDAR2B. Thus, we have shown that baseline reductions in cysteine underlie glutamatergic dysfunction and depressive-like behavior in HD and these changes can be rescued by treatment with NAC. These findings have implications for the development of new therapeutic approaches for depressive disorders. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Glutamatergic induction of CREB phosphorylation and Fos expression in primary cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate activity of NMDA and non-NMDA receptors.

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Schurov, I L; McNulty, S; Best, J D; Sloper, P J; Hastings, M H

1999-01-01

Exposure of Syrian hamsters to light 1 h after lights-off rapidly (10 min) induced nuclear immunoreactivity (-ir) to the phospho-Ser133 form of the Ca2+/cAMP response element (CRE) binding protein (pCREB) in the retinorecipient zone of the suprachiasmatic nuclei (SCN). Light also induced nuclear Fos-ir in the same region of the SCN after 1 h. The glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker MK801 attenuated the photic induction of both factors. To investigate glutamatergic regulation of pCREB and Fos further, tissue blocks and primary cultures of neonatal hamster SCN were examined by Western blotting and immunocytochemistry in vitro. On Western blots of SCN tissue, the pCREB-ir signal at 45 kDa was enhanced by glutamate or a mixture of glutamatergic agonists (NMDA, amino-methyl proprionic acid (AMPA), and Kainate (KA)), whereas total CREB did not change. Glutamate or the mixture of agonists also induced a 56 kDa band identified as Fos protein in SCN tissue. In dissociated cultures of SCN, glutamate caused a rapid (15 min) induction of nuclear pCREB-ir and Fos-ir (after 60 min) exclusively in neurones, both GABA-ir and others. Treatment with NMDA alone had no effect on pCREB-ir. AMPA alone caused a slight increase in pCREB-ir. However, kainate alone or in combination with NMDA and AMPA induced nuclear pCREB-ir equal to that induced by glutamate. The effects of glutamate on pCREB-ir and Fos-ir were blocked by antagonists of both NMDA (MK801) and AMPA/KA (NBQX) receptors. In the absence of extracellular Mg2+, MK801 blocked glutamatergic induction of Fos-ir. However, the AMPA/KA receptor antagonist was no longer effective at blocking glutamatergic induction of either Fos-ir or pCREB-ir, consistent with the model that glutamate regulates gene expression in the SCN by a co-ordinate action through both NMDA and AMPA/KA receptors. Glutamatergic induction of nuclear pCREB-ir in GABA-ir neurones was blocked by KN-62 an inhibitor of Ca2+/Calmodulin (Ca

Revisão: Composição química, propriedades funcionais e aplicações tecnológicas da semente de chia (Salvia hispanica L) em alimentos

OpenAIRE

Coelho, Michele Silveira; Salas-Mellado, Myriam de Las Mercedes

2014-01-01

A chia (Salvia hispanica L.) é uma semente antiga utilizada pelos maias e astecas como alimento para aumentar a resistência física. Essa semente é fonte natural de ácidos graxos ômega-3, fibras e proteínas, além de outros componentes nutricionais importantes, como os antioxidantes. Além disso, oferece um potencial na indústria de alimentos devido aos seus componentes funcionais, com aplicações no enriquecimento de pães, bolos e barras de cereais, produção de hidrolisados proteicos para aplica...

Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

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Grande, Giovanbattista; Negandhi, Jaina; Harrison, Robert V; Wang, Lu-Yang

2014-04-01

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity

Specific recycling receptors are targeted to the immune synapse by the intraflagellar transport system

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Finetti, Francesca; Patrussi, Laura; Masi, Giulia; Onnis, Anna; Galgano, Donatella; Lucherini, Orso Maria; Pazour, Gregory J.; Baldari, Cosima T.

2014-01-01

ABSTRACT T cell activation requires sustained signaling at the immune synapse, a specialized interface with the antigen-presenting cell (APC) that assembles following T cell antigen receptor (TCR) engagement by major histocompatibility complex (MHC)-bound peptide. Central to sustained signaling is the continuous recruitment of TCRs to the immune synapse. These TCRs are partly mobilized from an endosomal pool by polarized recycling. We have identified IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, as a central regulator of TCR recycling to the immune synapse. Here, we have investigated the interplay of IFT20 with the Rab GTPase network that controls recycling. We found that IFT20 forms a complex with Rab5 and the TCR on early endosomes. IFT20 knockdown (IFT20KD) resulted in a block in the recycling pathway, leading to a build-up of recycling TCRs in Rab5+ endosomes. Recycling of the transferrin receptor (TfR), but not of CXCR4, was disrupted by IFT20 deficiency. The IFT components IFT52 and IFT57 were found to act together with IFT20 to regulate TCR and TfR recycling. The results provide novel insights into the mechanisms that control TCR recycling and immune synapse assembly, and underscore the trafficking-related function of the IFT system beyond ciliogenesis. PMID:24554435

Mucilage from seeds of chia (Salvia hispanica L.) used as soil conditioner; effects on the sorption-desorption of four herbicides in three different soils.

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Di Marsico, A; Scrano, L; Amato, M; Gàmiz, B; Real, M; Cox, L

2018-06-01

The objective of this work was to determine the effect of the mucilage extracted from Chia seeds (Salvia hispanica L.) as soil amendment on soil physical properties and on the sorption-desorption behaviour of four herbicides (MCPA, Diuron, Clomazone and Terbuthylazine) used in cereal crops. Three soils of different texture (sandy-loam, loam and clay-loam) were selected, and mercury intrusion porosimetry and surface area analysis were used to examine changes in the microstructural characteristics caused by the reactions that occur between the mucilage and soil particles. Laboratory studies were conducted to characterise the selected herbicides with regard their sorption on tested soils added or not with the mucilage. Mucilage amendment resulted in a reduction in soil porosity, basically due to a reduction in larger pores (radius>10μm) and an important increase in finer pores (radius<10μm) and in partcles' surface. A higher herbicide sorption in the amended soils was ascertained when compared to unamended soils. The sorption percentage of herbicides in soils treated with mucilage increased in the order; sandy-loamChia seeds used as soil conditioner can reduce the mobility of herbicides tested in agricultural soils with different physico-chemical properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

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Meredith, Rhiannon M.; van Ooyen, Arjen

2012-01-01

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity.

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Hu, Jiang-Yuan; Schacher, Samuel

2014-04-02

Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.

Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism

DEFF Research Database (Denmark)

Silva, Guilherme Testa; Le Bé, Jean-Vincent; Riachi, Imad

2009-01-01

A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and ...... and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (...

Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

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Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

2018-02-21

Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction.

Science.gov (United States)

Saha, Rinki; Knapp, Stephanie; Chakraborty, Darpan; Horovitz, Omer; Albrecht, Anne; Kriebel, Martin; Kaphzan, Hanoch; Ehrlich, Ingrid; Volkmer, Hansjürgen; Richter-Levin, Gal

2017-01-01

Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum-BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum-BLA-LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

Three-terminal ferroelectric synapse device with concurrent learning function for artificial neural networks

International Nuclear Information System (INIS)

Nishitani, Y.; Kaneko, Y.; Ueda, M.; Fujii, E.; Morie, T.

2012-01-01

Spike-timing-dependent synaptic plasticity (STDP) is demonstrated in a synapse device based on a ferroelectric-gate field-effect transistor (FeFET). STDP is a key of the learning functions observed in human brains, where the synaptic weight changes only depending on the spike timing of the pre- and post-neurons. The FeFET is composed of the stacked oxide materials with ZnO/Pr(Zr,Ti)O 3 (PZT)/SrRuO 3 . In the FeFET, the channel conductance can be altered depending on the density of electrons induced by the polarization of PZT film, which can be controlled by applying the gate voltage in a non-volatile manner. Applying a pulse gate voltage enables the multi-valued modulation of the conductance, which is expected to be caused by a change in PZT polarization. This variation depends on the height and the duration of the pulse gate voltage. Utilizing these characteristics, symmetric and asymmetric STDP learning functions are successfully implemented in the FeFET-based synapse device by applying the non-linear pulse gate voltage generated from a set of two pulses in a sampling circuit, in which the two pulses correspond to the spikes from the pre- and post-neurons. The three-terminal structure of the synapse device enables the concurrent learning, in which the weight update can be performed without canceling signal transmission among neurons, while the neural networks using the previously reported two-terminal synapse devices need to stop signal transmission for learning.

Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

Directory of Open Access Journals (Sweden)

Lisa eMapelli

2015-05-01

Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

Science.gov (United States)

Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

2015-01-01

The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

Detection of mecA Gene Associated with Methicillin Resistant Staphylococcus aureus and its Alternatives using Nanoparticles and Chia Seeds

Directory of Open Access Journals (Sweden)

M. Rajamani

2017-11-01

Full Text Available Staphylococcus aureus, a member of the family Micrococcaceae, is a Gram-positive coccus whose cells tend to occur either singly or if dividing cells do not separate, form pairs, tetrads and distinctive irregular “grape-like” structures, which is resistant to few antibiotics like Methicillin which is termed as Methicillin resistant Staphylococcus aureus. MRSA was isolated from the pus sample. Confirmation of MRSA was done by using Kirby Bauer disk method. Followed by sub culturing in Luria bertani broth and DNA isolation was performed by phenol chloroform method and confirmed by AGE (Agarose gel electrophoresis. The amplification of mecA gene thermocycler-PCR was done. Restriction fragmented linked polymorphism was done for knowing how much restriction sites are available for organism. To calculate the molecular weight of the protein SDS-PAGE (Sodium dodecyl sulphate - Polyacrylamide gel electrophoresis was performed. Followed by alternative measures was done, by using Silver nanoparticles at different concentrations and Chia seeds against MRSA.

Mixed Analog/Digital Matrix-Vector Multiplier for Neural Network Synapses

DEFF Research Database (Denmark)

Lehmann, Torsten; Bruun, Erik; Dietrich, Casper

1996-01-01

In this work we present a hardware efficient matrix-vector multiplier architecture for artificial neural networks with digitally stored synapse strengths. We present a novel technique for manipulating bipolar inputs based on an analog two's complements method and an accurate current rectifier...

Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy : a multimodal fMRI-MRS study

NARCIS (Netherlands)

Modinos, G; McLaughlin, A; Egerton, A; McMullen, K; Kumari, V; Barker, G J; Keysers, C; Williams, S C R

2017-01-01

Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to

Corticolimbic hyper-response to emotion and glutamatergic function in people with high schizotypy: a multimodal fMRI-MRS study

NARCIS (Netherlands)

Modinos, G.; McLaughlin, A.; Egerton, A.; McMullen, K.; Kumari, V.; Barker, G.J.; Keysers, C.; Williams, S.C.R.

2017-01-01

Animal models and human neuroimaging studies suggest that altered levels of glutamatergic metabolites within a corticolimbic circuit have a major role in the pathophysiology of schizophrenia. Rodent models propose that prefrontal glutamate dysfunction could lead to amygdala hyper-response to

A Computational Model to Investigate Astrocytic Glutamate Uptake Influence on Synaptic Transmission and Neuronal Spiking

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Sushmita Lakshmi Allam

2012-10-01

Full Text Available Over the past decades, our view of astrocytes has switched from passive support cells to active processing elements in the brain. The current view is that astrocytes shape neuronal communication and also play an important role in many neurodegenerative diseases. Despite the growing awareness of the importance of astrocytes, the exact mechanisms underlying neuron-astrocyte communication and the physiological consequences of astrocytic-neuronal interactions remain largely unclear. In this work, we define a modeling framework that will permit to address unanswered questions regarding the role of astrocytes. Our computational model of a detailed glutamatergic synapse facilitates the analysis of neural system responses to various stimuli and conditions that are otherwise difficult to obtain experimentally, in particular the readouts at the sub-cellular level. In this paper, we extend a detailed glutamatergic synaptic model, to include astrocytic glutamate transporters. We demonstrate how these glial transporters, responsible for the majority of glutamate uptake, modulate synaptic transmission mediated by ionotropic AMPA and NMDA receptors at glutamatergic synapses. Furthermore, we investigate how these local signaling effects at the synaptic level are translated into varying spatio-temporal patterns of neuron firing. Paired pulse stimulation results reveal that the effect of astrocytic glutamate uptake is more apparent when the input inter-spike interval is sufficiently long to allow the receptors to recover from desensitization. These results suggest an important functional role of astrocytes in spike timing dependent processes and demand further investigation of the molecular basis of certain neurological diseases specifically related to alterations in astrocytic glutamate uptake, such as epilepsy.

The interplay between neurons and glia in synapse development and plasticity.

Science.gov (United States)

Stogsdill, Jeff A; Eroglu, Cagla

2017-02-01

In the brain, the formation of complex neuronal networks amenable to experience-dependent remodeling is complicated by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on neurons, but also non-neuronal glial cells. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This article reviews important findings, which uncovered cellular and molecular aspects of the neuron-glia cross-talk that govern the formation and remodeling of synapses and circuits. In vivo evidence demonstrating the critical interplay between neurons and glia will be the major focus. Additional attention will be given to how aberrant communication between neurons and glia may contribute to neural pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synapse:neural network for predict power consumption: users guide

Energy Technology Data Exchange (ETDEWEB)

Muller, C; Mangeas, M; Perrot, N

1994-08-01

SYNAPSE is forecasting tool designed to predict power consumption in metropolitan France on the half hour time scale. Some characteristics distinguish this forecasting model from those which already exist. In particular, it is composed of numerous neural networks. The idea for using many neural networks arises from past tests. These tests showed us that a single neural network is not able to solve the problem correctly. From this result, we decided to perform unsupervised classification of the 24 consumption curves. From this classification, six classes appeared, linked with the weekdays: Mondays, Tuesdays, Wednesdays, Thursdays, Fridays, Saturdays, Sundays, holidays and bridge days. For each class and for each half hour, two multilayer perceptrons are built. The two of them forecast the power for one particular half hour, and for a day including one of the determined class. The input of these two network are different: the first one (short time forecasting) includes the powers for the most recent half hour and relative power of the previous day; the second (medium time forecasting) includes only the relative power of the previous day. A process connects the results of every networks and allows one to forecast more than one half-hour in advance. In this process, short time forecasting networks and medium time forecasting networks are used differently. The first kind of neural networks gives good results on the scale of one day. The second one gives good forecasts for the next predicted powers. In this note, the organization of the SYNAPSE program is detailed, and the user`s menu is described. This first version of synapse works and should allow the APC group to evaluate its utility. (authors). 6 refs., 2 appends.

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

Science.gov (United States)

Tang, Sheng; Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara; Pance, Katarina; Lee, Jun Y; Cui, Yue; Coulter, Douglas A; Zhou, Zhaolan

2017-08-02

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and

Exercise training lowers the enhanced tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.

Science.gov (United States)

Zha, Yan-Ping; Wang, Yang-Kai; Deng, Yu; Zhang, Ru-Wen; Tan, Xing; Yuan, Wen-Jun; Deng, Xiao-Ming; Wang, Wei-Zhong

2013-04-01

It is well known that low-intensity exercise training (ExT) is beneficial to cardiovascular dysfunction in hypertension. The tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM), a key region for control of blood pressure and sympathetic tone, has been demonstrated to be increased in hypertensive rats. The aim of this study was to determine the effect of ExT on the increased glutamatergic input to the RVLM in spontaneously hypertensive rat (SHR). Normotensive rats Wistar-Kyoto (WKY) and SHR were treadmill trained or remained sedentary (Sed) for 12 weeks and classed into four groups (WKY-Sed, WKY-ExT, SHR-Sed, and SHR-ExT). The release of glutamate in the RVLM and its contribution to cardiovascular activity were determined in WKY and SHR after treatment of ExT. Blood pressure and sympathetic tone were significantly reduced in SHR after treatment with ExT. Bilateral microinjection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nL) into the RVLM significantly decreased resting blood pressure, heart rate, and renal sympathetic nerve activity in SHR-Sed but not in WKY groups (WKY-Sed and WKY-ExT). However, the degree of reduction in these cardiovascular parameters evoked by KYN was significantly blunted in SHR-ExT compared with SHR-Sed group. The concentration of glutamate and the protein expression of vesicular glutamate transporter 2 in the RVLM were significantly increased in SHR-Sed compared with WKY-Sed, whereas they were reduced after treatment with ExT. Our findings suggest that ExT attenuates the enhancement in the tonically acting glutamatergic input to the RVLM of hypertensive rats, thereby reducing the sympathetic hyperactivity and blood pressure. © 2013 Blackwell Publishing Ltd.

A Neuron- and a Synapse Chip for Artificial Neural Networks

DEFF Research Database (Denmark)

Lansner, John; Lehmann, Torsten

1992-01-01

A cascadable, analog, CMOS chip set has been developed for hardware implementations of artificial neural networks (ANN's):I) a neuron chip containing an array of neurons with hyperbolic tangent activation functions and adjustable gains, and II) a synapse chip (or a matrix-vector multiplier) where...

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity.

Science.gov (United States)

Moeller, Scott J; London, Edythe D; Northoff, Georg

2016-02-01

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Machine Learning Method for the Prediction of Receptor Activation in the Simulation of Synapses

Science.gov (United States)

Montes, Jesus; Gomez, Elena; Merchán-Pérez, Angel; DeFelipe, Javier; Peña, Jose-Maria

2013-01-01

Chemical synaptic transmission involves the release of a neurotransmitter that diffuses in the extracellular space and interacts with specific receptors located on the postsynaptic membrane. Computer simulation approaches provide fundamental tools for exploring various aspects of the synaptic transmission under different conditions. In particular, Monte Carlo methods can track the stochastic movements of neurotransmitter molecules and their interactions with other discrete molecules, the receptors. However, these methods are computationally expensive, even when used with simplified models, preventing their use in large-scale and multi-scale simulations of complex neuronal systems that may involve large numbers of synaptic connections. We have developed a machine-learning based method that can accurately predict relevant aspects of the behavior of synapses, such as the percentage of open synaptic receptors as a function of time since the release of the neurotransmitter, with considerably lower computational cost compared with the conventional Monte Carlo alternative. The method is designed to learn patterns and general principles from a corpus of previously generated Monte Carlo simulations of synapses covering a wide range of structural and functional characteristics. These patterns are later used as a predictive model of the behavior of synapses under different conditions without the need for additional computationally expensive Monte Carlo simulations. This is performed in five stages: data sampling, fold creation, machine learning, validation and curve fitting. The resulting procedure is accurate, automatic, and it is general enough to predict synapse behavior under experimental conditions that are different to the ones it has been trained on. Since our method efficiently reproduces the results that can be obtained with Monte Carlo simulations at a considerably lower computational cost, it is suitable for the simulation of high numbers of synapses and it is

A machine learning method for the prediction of receptor activation in the simulation of synapses.

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Jesus Montes

Full Text Available Chemical synaptic transmission involves the release of a neurotransmitter that diffuses in the extracellular space and interacts with specific receptors located on the postsynaptic membrane. Computer simulation approaches provide fundamental tools for exploring various aspects of the synaptic transmission under different conditions. In particular, Monte Carlo methods can track the stochastic movements of neurotransmitter molecules and their interactions with other discrete molecules, the receptors. However, these methods are computationally expensive, even when used with simplified models, preventing their use in large-scale and multi-scale simulations of complex neuronal systems that may involve large numbers of synaptic connections. We have developed a machine-learning based method that can accurately predict relevant aspects of the behavior of synapses, such as the percentage of open synaptic receptors as a function of time since the release of the neurotransmitter, with considerably lower computational cost compared with the conventional Monte Carlo alternative. The method is designed to learn patterns and general principles from a corpus of previously generated Monte Carlo simulations of synapses covering a wide range of structural and functional characteristics. These patterns are later used as a predictive model of the behavior of synapses under different conditions without the need for additional computationally expensive Monte Carlo simulations. This is performed in five stages: data sampling, fold creation, machine learning, validation and curve fitting. The resulting procedure is accurate, automatic, and it is general enough to predict synapse behavior under experimental conditions that are different to the ones it has been trained on. Since our method efficiently reproduces the results that can be obtained with Monte Carlo simulations at a considerably lower computational cost, it is suitable for the simulation of high numbers of

Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Naaijen, Jill; Bralten, Janita; Poelmans, Geert

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance...... within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms...... is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants...

Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

OpenAIRE

Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J.

2016-01-01

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discriminatio...

A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia.

Science.gov (United States)

Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

2012-08-28

The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

Building blocks of temporal filters in retinal synapses.

Directory of Open Access Journals (Sweden)

Bongsoo Suh

2014-10-01

Full Text Available Sensory systems must be able to extract features of a stimulus to detect and represent properties of the world. Because sensory signals are constantly changing, a critical aspect of this transformation relates to the timing of signals and the ability to filter those signals to select dynamic properties, such as visual motion. At first assessment, one might think that the primary biophysical properties that construct a temporal filter would be dynamic mechanisms such as molecular concentration or membrane electrical properties. However, in the current issue of PLOS Biology, Baden et al. identify a mechanism of temporal filtering in the zebrafish and goldfish retina that is not dynamic but is in fact a structural building block-the physical size of a synapse itself. The authors observe that small, bipolar cell synaptic terminals are fast and highly adaptive, whereas large ones are slower and adapt less. Using a computational model, they conclude that the volume of the synaptic terminal influences the calcium concentration and the number of available vesicles. These results indicate that the size of the presynaptic terminal is an independent control for the dynamics of a synapse and may reveal aspects of synaptic function that can be inferred from anatomical structure.

Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

Science.gov (United States)

Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

2008-02-28

The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

Loss of Synapse Repressor MDGA1 Enhances Perisomatic Inhibition, Confers Resistance to Network Excitation, and Impairs Cognitive Function

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Steven A. Connor

2017-12-01

Full Text Available Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses. Mdga1−/− hippocampal networks demonstrate muted responses to neural excitation, and Mdga1−/− mice are resistant to induced seizures. Mdga1−/− mice further demonstrate compromised hippocampal long-term potentiation, consistent with observed deficits in spatial and context-dependent learning and memory. These results suggest that mutations in MDGA1 may contribute to cognitive deficits through altered synaptic transmission and plasticity by loss of suppression of inhibitory synapse development in a subcellular domain- and cell-type-selective manner.

On optical detection of densely labeled synapses in neuropil and mapping connectivity with combinatorially multiplexed fluorescent synaptic markers.

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Yuriy Mishchenko

Full Text Available We propose a new method for mapping neural connectivity optically, by utilizing Cre/Lox system Brainbow to tag synapses of different neurons with random mixtures of different fluorophores, such as GFP, YFP, etc., and then detecting patterns of fluorophores at different synapses using light microscopy (LM. Such patterns will immediately report the pre- and post-synaptic cells at each synaptic connection, without tracing neural projections from individual synapses to corresponding cell bodies. We simulate fluorescence from a population of densely labeled synapses in a block of hippocampal neuropil, completely reconstructed from electron microscopy data, and show that high-end LM is able to detect such patterns with over 95% accuracy. We conclude, therefore, that with the described approach neural connectivity in macroscopically large neural circuits can be mapped with great accuracy, in scalable manner, using fast optical tools, and straightforward image processing. Relying on an electron microscopy dataset, we also derive and explicitly enumerate the conditions that should be met to allow synaptic connectivity studies with high-resolution optical tools.

Generation of functional inhibitory synapses incorporating defined combinations of GABA(A or glycine receptor subunits

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Christine Laura Dixon

2015-12-01

Full Text Available Fast inhibitory neurotransmission in the brain is mediated by wide range of GABAA receptor (GABAAR and glycine receptor (GlyR isoforms, each with different physiological and pharmacological properties. Because multiple isoforms are expressed simultaneously in most neurons, it is difficult to define the properties of inhibitory postsynaptic currents mediated by individual isoforms in vivo. Although recombinant expression systems permit the expression of individual isoforms in isolation, they require exogenous agonist application which cannot mimic the dynamic neurotransmitter profile characteristic of native synapses. We describe a neuron-HEK293 cell co-culture technique for generating inhibitory synapses incorporating defined combinations of GABAAR or GlyR subunits. Primary neuronal cultures, prepared from embryonic rat cerebral cortex or spinal cord, are used to provide presynaptic GABAergic and glycinergic terminals, respectively. When the cultures are mature, HEK293 cells expressing the subunits of interest plus neuroligin 2A are plated onto the neurons, which rapidly form synapses onto HEK293 cells. Patch clamp electrophysiology is then used to analyze the physiological and pharmacological properties of the inhibitory postsynaptic currents mediated by the recombinant receptors. The method is suitable for investigating the kinetic properties or the effects of drugs on inhibitory postsynaptic currents mediated by defined GABAAR or GlyR isoforms of interest, the effects of hereditary disease mutations on the formation and function of both types of synapses, and synaptogenesis and synaptic clustering mechanisms. The entire cell preparation procedure takes 2 – 5 weeks.

Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder.

Science.gov (United States)

Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Melton, Tabatha; Buyukdura, Jeylan S; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

2013-03-01

Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

P2X7 Receptors Drive Spine Synapse Plasticity in the Learned Helplessness Model of Depression.

Science.gov (United States)

Otrokocsi, Lilla; Kittel, Ágnes; Sperlágh, Beáta

2017-10-01

Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments; however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet. Effects of genetic deletion of P2rx7s on depressive-like behavior and spine synapse density in the dentate gyrus were investigated using the learned helplessness mouse model of depression. We demonstrate that in wild-type animals, inescapable footshocks lead to learned helplessness behavior reflected in increased latency and number of escape failures to subsequent escapable footshocks. This behavior is accompanied with downregulation of mRNA encoding P2rx7 and decrease of spine synapse density in the dentate gyrus as determined by electron microscopic stereology. In addition, a decrease in synaptopodin but not in PSD95 and NR2B/GluN2B protein level was also observed under these conditions. Whereas the absence of P2rx7 was characterized by escape deficit, no learned helpless behavior is observed in these animals. Likewise, no decrease in spine synapse number and synaptopodin protein levels was detected in response to inescapable footshocks in P2rx7-deficient animals. Our findings suggest the endogenous activation of P2rx7s in the learned helplessness model of depression and decreased plasticity of spine synapses in P2rx7-deficient mice might explain the resistance of these animals to repeated stressful stimuli. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Storage capacity of attractor neural networks with depressing synapses

International Nuclear Information System (INIS)

Torres, Joaquin J.; Pantic, Lovorka; Kappen, Hilbert J.

2002-01-01

We compute the capacity of a binary neural network with dynamic depressing synapses to store and retrieve an infinite number of patterns. We use a biologically motivated model of synaptic depression and a standard mean-field approach. We find that at T=0 the critical storage capacity decreases with the degree of the depression. We confirm the validity of our main mean-field results with numerical simulations

Glutamatergic synaptic currents of nigral dopaminergic neurons follow a postnatal developmental sequence

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Edouard ePearlstein

2015-05-01

Full Text Available The spontaneous activity pattern of adult dopaminergic (DA neurons of the substantia nigra pars compacta (SNc results from interactions between intrinsic membrane conductances and afferent inputs. In adult SNc DA neurons, low-frequency tonic background activity is generated by intrinsic pacemaker mechanisms, whereas burst generation depends on intact synaptic inputs in particular the glutamatergic ones. Tonic DA release in the striatum during pacemaking is required to maintain motor activity, and burst firing evokes phasic DA release, necessary for cue-dependent learning tasks. However, it is still unknown how the firing properties of SNc DA neurons mature during postnatal development before reaching the adult state. We studied the postnatal developmental profile of spontaneous and evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs in SNc DA neurons in brain slices from immature (postnatal days P4-10 and young adult (P30-50 tyrosine hydroxylase (TH-GFP mice. We found that somato-dendritic fields of SNc DA neurons are already mature at P4-10. In contrast, spontaneous glutamatergic EPSCs show a developmental sequence. Spontaneous NMDA EPSCs in particular are larger and more frequent in immature SNc DA neurons than in young adult ones and have a bursty pattern. They are mediated by GluN2B and GluN2D subunit-containing NMDA receptors. The latter generate long-lasting, DQP1105-sensitive, spontaneous EPSCs, which are transiently recorded during this early period. Due to high NMDA activity, immature SNc DA neurons generate large and long lasting NMDA receptor-dependent (APV-sensitive bursts in response to the stimulation of the subthalamic nucleus. We conclude that the transient high NMDA activity allows calcium influx into the dendrites of developing SNc DA neurons.

Endocannabinoids and the processing of value-related signals

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Miriam eMelis

2012-02-01

Full Text Available Endocannabinoids serve as retrograde signaling molecules at many synapses within the CNS, particularly GABAergic and glutamatergic synapses. Synapses onto midbrain dopamine (DA neurons in the ventral tegmental area (VTA make no exception to this rule. In fact, the effects of cannabinoids on dopamine transmission as well as DA-related behaviors are generally exerted through the modulation of inhibitory and excitatory afferents impinging onto DA neurons. Endocannabinoids, by regulating different forms of synaptic plasticity in the VTA, provide a critical modulation of the DA neuron output and, ultimately, of the systems driving and regulating motivated behaviors. Because DA cells exhibit diverse states of activity, which crucially depend on their intrinsic properties and afferent drive, the understanding of the role played by endocannabinoids in synaptic modulations is critical for their overall functions. Particularly, endocannabinoids by selectively inhibiting afferent activity may alter the functional states of DA neurons and potentiate the responsiveness of the reward system to phasic DA.

Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

NARCIS (Netherlands)

Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane

2016-01-01

Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying

Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T.

Science.gov (United States)

Joshi, Gagan; Biederman, Joseph; Wozniak, Janet; Goldin, Rachel L; Crowley, Dave; Furtak, Stephannie; Lukas, Scott E; Gönenç, Atilla

2013-08-01

The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 ± 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 ± 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample.

Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress

Science.gov (United States)

Xu, Aiping; Cui, Shan

2016-01-01

Background: Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice. Methods: Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls. Results: In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness. Conclusions: Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders. PMID:26506857

A 2-transistor/1-resistor artificial synapse capable of communication and stochastic learning in neuromorphic systems.

Science.gov (United States)

Wang, Zhongqiang; Ambrogio, Stefano; Balatti, Simone; Ielmini, Daniele

2014-01-01

Resistive (or memristive) switching devices based on metal oxides find applications in memory, logic and neuromorphic computing systems. Their small area, low power operation, and high functionality meet the challenges of brain-inspired computing aiming at achieving a huge density of active connections (synapses) with low operation power. This work presents a new artificial synapse scheme, consisting of a memristive switch connected to 2 transistors responsible for gating the communication and learning operations. Spike timing dependent plasticity (STDP) is achieved through appropriate shaping of the pre-synaptic and the post synaptic spikes. Experiments with integrated artificial synapses demonstrate STDP with stochastic behavior due to (i) the natural variability of set/reset processes in the nanoscale switch, and (ii) the different response of the switch to a given stimulus depending on the initial state. Experimental results are confirmed by model-based simulations of the memristive switching. Finally, system-level simulations of a 2-layer neural network and a simplified STDP model show random learning and recognition of patterns.

The State of Synapses in Fragile X Syndrome

OpenAIRE

Pfeiffer, Brad E.; Huber, Kimberly M.

2009-01-01

Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP. Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is...

Emerging phenomena in neural networks with dynamic synapses and their computational implications

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Joaquin J. eTorres

2013-04-01

Full Text Available In this paper we review our research on the effect and computational role of dynamical synapses on feed-forward and recurrent neural networks. Among others, we report on the appearance of a new class of dynamical memories which result from the destabilisation of learned memory attractors. This has important consequences for dynamic information processing allowing the system to sequentially access the information stored in the memories under changing stimuli. Although storage capacity of stable memories also decreases, our study demonstrated the positive effect of synaptic facilitation to recover maximum storage capacity and to enlarge the capacity of the system for memory recall in noisy conditions. Possibly, the new dynamical behaviour can be associated with the voltage transitions between up and down states observed in cortical areas in the brain. We investigated the conditions for which the permanence times in the up state are power-law distributed, which is a sign for criticality, and concluded that the experimentally observed large variability of permanence times could be explained as the result of noisy dynamic synapses with large recovery times. Finally, we report how short-term synaptic processes can transmit weak signals throughout more than one frequency range in noisy neural networks, displaying a kind of stochastic multi-resonance. This effect is due to competition between activity-dependent synaptic fluctuations (due to dynamic synapses and the existence of neuron firing threshold which adapts to the incoming mean synaptic input.

Low-doses of cisplatin injure hippocampal synapses: a mechanism for 'chemo' brain?

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Andres, Adrienne L; Gong, Xing; Di, Kaijun; Bota, Daniela A

2014-05-01

Chemotherapy-related cognitive deficits are a major neurological problem, but the underlying mechanisms are unclear. The death of neural stem/precursor cell (NSC) by cisplatin has been reported as a potential cause, but this requires high doses of chemotherapeutic agents. Cisplatin is frequently used in modern oncology, and it achieves high concentrations in the patient's brain. Here we report that exposure to low concentrations of cisplatin (0.1μM) causes the loss of dendritic spines and synapses within 30min. Longer exposures injured dendritic branches and reduced dendritic complexity. At this low concentration, cisplatin did not affect NSC viability nor provoke apoptosis. However, higher cisplatin levels (1μM) led to the rapid loss of synapses and dendritic disintegration, and neuronal-but not NSC-apoptosis. In-vivo treatment with cisplatin at clinically relevant doses also caused a reduction of dendritic branches and decreased spine density in CA1 and CA3 hippocampal neurons. An acute increase in cell death was measured in the CA1 and CA3 neurons, as well as in the NSC population located in the subgranular zone of the dentate gyrus in the cisplatin treated animals. The density of dendritic spines is related to the degree of neuronal connectivity and function, and pathological changes in spine number or structure have significant consequences for brain function. Therefore, this synapse and dendritic damage might contribute to the cognitive impairment observed after cisplatin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Cux1 and Cux2 regulate dendritic branching, spine morphology and synapses of the upper layer neurons of the cortex

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Cubelos, Beatriz; Sebastián-Serrano, Alvaro; Beccari, Leonardo; Calcagnotto, Maria Elisa; Cisneros, Elsa; Kim, Seonhee; Dopazo, Ana; Alvarez-Dolado, Manuel; Redondo, Juan Miguel; Bovolenta, Paola; Walsh, Christopher A.; Nieto, Marta

2010-01-01

Summary Dendrite branching and spine formation determines the function of morphologically distinct and specialized neuronal subclasses. However, little is known about the programs instructing specific branching patterns in vertebrate neurons and whether such programs influence dendritic spines and synapses. Using knockout and knockdown studies combined with morphological, molecular and electrophysiological analysis we show that the homeobox Cux1 and Cux2 are intrinsic and complementary regulators of dendrite branching, spine development and synapse formation in layer II–III neurons of the cerebral cortex. Cux genes control the number and maturation of dendritic spines partly through direct regulation of the expression of Xlr3b and Xlr4b, chromatin remodeling genes previously implicated in cognitive defects. Accordingly, abnormal dendrites and synapses in Cux2−/− mice correlate with reduced synaptic function and defects in working memory. These demonstrate critical roles of Cux in dendritogenesis and highlight novel subclass-specific mechanisms of synapse regulation that contribute to the establishment of cognitive circuits. PMID:20510857

Epidemics in Ming and Qing China: Impacts of changes of climate and economic well-being.

Science.gov (United States)

Pei, Qing; Zhang, David D; Li, Guodong; Winterhalder, Bruce; Lee, Harry F

2015-07-01

We investigated the mechanism of epidemics with the impacts of climate change and socio-economic fluctuations in the Ming and Qing Dynasties in China (AD 1368-1901). Using long-term and high-quality datasets, this study is the first quantitative research that verifies the 'climate change → economy → epidemics' mechanism in historical China by statistical methods that include correlation analysis, Granger causality analysis, ARX, and Poisson-ARX modeling. The analysis provides the evidences that climate change could only fundamentally lead to the epidemics spread and occurrence, but the depressed economic well-being is the direct trigger of epidemics spread and occurrence at the national and long term scale in historical China. Moreover, statistical modeling shows that economic well-being is more important than population pressure in the mechanism of epidemics. However, population pressure remains a key element in determining the social vulnerability of the epidemics occurrence under climate change. Notably, the findings not only support adaptation theories but also enhance our confidence to address climatic shocks if economic buffering capacity can be promoted steadily. The findings can be a basis for scientists and policymakers in addressing global and regional environmental changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

Science.gov (United States)

Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

2014-05-01

Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

Marriages Awakening the World and Shangdong’s Birthday Celebration Custom in Ming and Qing Dynasty%从«醒世姻缘传»看明清山东的寿诞礼俗

Institute of Scientific and Technical Information of China (English)

吕文娟; 魏红

2014-01-01

Marriages Awakening the World (Xingshi Yinyuan Zhuan )is an important novel aboutMmarriage and family life,published subsequent to J inpingmei Cihua and prior to A Dream of Redansions .Its vivid portrayal of etiquette in the Ming and Qing Dynasties provides bountiful material for the study on life etiquette of that historical period.This thesis makes a systematic probe into the folkways in Shandong reflected in Marriages Awakening the World so as to gain a good understanding of the panorama and characteristics of Shandong folk culture in the Ming and Qing Dynasties.To bemore exact,this study investigates birth- and birthday-celebrating customs in Shandong in detail,un-veiling their underlying cultural meanings.It also delves into the social,cultural and literary Asignificance of the life etiquette in Shandong in the Ming and Qing dynasties reflected in Marriageswakening the World .%«醒世姻缘传»是«金瓶梅词话»之后、«红楼梦»之前的一部重要的以婚姻家庭生活为题材的小说，生动地再现了当时民间礼俗的状态，为我们研究明清时期的人生礼俗提供了宝贵的资料。文章主要探讨该小说与明清山东的寿诞礼俗，分别对诞生礼俗和庆寿礼俗作了详细的描述，并揭示其中所蕴含着的文化意义；对«醒世姻缘传»所反映出的明清山东人生礼俗的社会、文化及文学意义进行阐释。

Cytoskeletal actin dynamics shape a ramifying actin network underpinning immunological synapse formation

DEFF Research Database (Denmark)

Fritzsche, Marco; Fernandes, Ricardo A.; Chang, Veronica T.

2017-01-01

optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...

Lamina-specific contribution of glutamatergic and GABAergic potentials to hippocampal sharp wave-ripple complexes.

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Schönberger, Jan; Draguhn, Andreas; Both, Martin

2014-01-01

The mammalian hippocampus expresses highly organized patterns of neuronal activity which form a neuronal correlate of spatial memories. These memory-encoding neuronal ensembles form on top of different network oscillations which entrain neurons in a state- and experience-dependent manner. The mechanisms underlying activation, timing and selection of participating neurons are incompletely understood. Here we studied the synaptic mechanisms underlying one prominent network pattern called sharp wave-ripple complexes (SPW-R) which are involved in memory consolidation during sleep. We recorded SPW-R with extracellular electrodes along the different layers of area CA1 in mouse hippocampal slices. Contribution of glutamatergic excitation and GABAergic inhibition, respectively, was probed by local application of receptor antagonists into s. radiatum, pyramidale and oriens. Laminar profiles of field potentials show that GABAergic potentials contribute substantially to sharp waves and superimposed ripple oscillations in s. pyramidale. Inhibitory inputs to s. pyramidale and s. oriens are crucial for action potential timing by ripple oscillations, as revealed by multiunit-recordings in the pyramidal cell layer. Glutamatergic afferents, on the other hand, contribute to sharp waves in s. radiatum where they also evoke a fast oscillation at ~200 Hz. Surprisingly, field ripples in s. radiatum are slightly slower than ripples in s. pyramidale, resulting in a systematic shift between dendritic and somatic oscillations. This complex interplay between dendritic excitation and perisomatic inhibition may be responsible for the precise timing of discharge probability during the time course of SPW-R. Together, our data illustrate a complementary role of spatially confined excitatory and inhibitory transmission during highly ordered network patterns in the hippocampus.

Effects of dynamic synapses on noise-delayed response latency of a single neuron

Science.gov (United States)

Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

2015-12-01

The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

Anatomically detailed and large-scale simulations studying synapse loss and synchrony using NeuroBox

Directory of Open Access Journals (Sweden)

Markus eBreit

2016-02-01

Full Text Available The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic or reconstruction to the simulation platform UG 4 (which harbors a neuroscientific portfolio and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g. new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

Candidate glutamatergic neurons in the visual system of Drosophila.

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Shamprasad Varija Raghu

Full Text Available The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L, transmedullary (Tm, transmedullary Y (TmY, Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am, bushy T (T, translobula plate (Tlp, lobula intrinsic (Lcn, Lt, Li, lobula plate tangential (LPTCs and lobula plate intrinsic (LPi cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system.

Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

DEFF Research Database (Denmark)

Soricelli, A; Postiglione, A; Grivet-Fojaja, M R

1996-01-01

Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminat...... simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P...

Human synapses show a wide temporal window for spike-timing-dependent plasticity

NARCIS (Netherlands)

Testa-Silva, G.; Verhoog, M.B.; Goriounova, N.A.; Loebel, A.; Hjorth, J.; Baayen, J.C.; de Kock, C.P.J.; Mansvelder, H.D.

2010-01-01

Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter strength and the magnitude and sign depend on the millisecond timing of presynaptic and postsynaptic

The excitatory/inhibitory input to orexin/hypocretin neuron soma undergoes day/night reorganization.

Science.gov (United States)

Laperchia, Claudia; Imperatore, Roberta; Azeez, Idris A; Del Gallo, Federico; Bertini, Giuseppe; Grassi-Zucconi, Gigliola; Cristino, Luigia; Bentivoglio, Marina

2017-11-01

Orexin (OX)/hypocretin-containing neurons are main regulators of wakefulness stability, arousal, and energy homeostasis. Their activity varies in relation to the animal's behavioral state. We here tested whether such variation is subserved by synaptic plasticity phenomena in basal conditions. Mice were sacrificed during day or night, at times when sleep or wake, respectively, predominates, as assessed by electroencephalography in matched mice. Triple immunofluorescence was used to visualize OX-A perikarya and varicosities containing the vesicular glutamate transporter (VGluT)2 or the vesicular GABA transporter (VGAT) combined with synaptophysin (Syn) as a presynaptic marker. Appositions on OX-A + somata were quantitatively analyzed in pairs of sections in epifluorescence and confocal microscopy. The combined total number of glutamatergic (Syn + /VGluT2 + ) and GABAergic (Syn + /VGAT + ) varicosities apposed to OX-A somata was similar during day and night. However, glutamatergic varicosities were significantly more numerous at night, whereas GABAergic varicosities prevailed in the day. Triple immunofluorescence in confocal microscopy was employed to visualize synapse scaffold proteins as postsynaptic markers and confirmed the nighttime prevalence of VGluT2 + together with postsynaptic density protein 95 + excitatory contacts, and daytime prevalence of VGAT + together with gephyrin + inhibitory contacts, while also showing that they formed synapses on OX-A + cell bodies. The findings reveal a daily reorganization of axosomatic synapses in orexinergic neurons, with a switch from a prevalence of excitatory innervation at a time corresponding to wakefulness to a prevalence of inhibitory innervations in the antiphase, at a time corresponding to sleep. This reorganization could represent a key mechanism of plasticity of the orexinergic network in basal conditions.

Live cell linear dichroism imaging reveals extensive membrane ruffling within the docking structure of natural killer cell immune synapses

DEFF Research Database (Denmark)

Benninger, Richard K P; Vanherberghen, Bruno; Young, Stephen

2009-01-01

We have applied fluorescence imaging of two-photon linear dichroism to measure the subresolution organization of the cell membrane during formation of the activating (cytolytic) natural killer (NK) cell immune synapse (IS). This approach revealed that the NK cell plasma membrane is convoluted...... into ruffles at the periphery, but not in the center of a mature cytolytic NK cell IS. Time-lapse imaging showed that the membrane ruffles formed at the initial point of contact between NK cells and target cells and then spread radialy across the intercellular contact as the size of the IS increased, becoming...... absent from the center of the mature synapse. Understanding the role of such extensive membrane ruffling in the assembly of cytolytic synapses is an intriguing new goal....

Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

Science.gov (United States)

Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

2018-02-27

Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

From synapse to nucleus and back again--communication over distance within neurons.

Science.gov (United States)

Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A; Kreutz, Michael R

2011-11-09

How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.

The organization of plasticity in the cerebellar cortex: from synapses to control.

Science.gov (United States)

D'Angelo, Egidio

2014-01-01

The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

A Reinforcement Learning Framework for Spiking Networks with Dynamic Synapses

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Karim El-Laithy

2011-01-01

Full Text Available An integration of both the Hebbian-based and reinforcement learning (RL rules is presented for dynamic synapses. The proposed framework permits the Hebbian rule to update the hidden synaptic model parameters regulating the synaptic response rather than the synaptic weights. This is performed using both the value and the sign of the temporal difference in the reward signal after each trial. Applying this framework, a spiking network with spike-timing-dependent synapses is tested to learn the exclusive-OR computation on a temporally coded basis. Reward values are calculated with the distance between the output spike train of the network and a reference target one. Results show that the network is able to capture the required dynamics and that the proposed framework can reveal indeed an integrated version of Hebbian and RL. The proposed framework is tractable and less computationally expensive. The framework is applicable to a wide class of synaptic models and is not restricted to the used neural representation. This generality, along with the reported results, supports adopting the introduced approach to benefit from the biologically plausible synaptic models in a wide range of intuitive signal processing.

Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimer's Disease

Science.gov (United States)

Wilke, Scott A.; Raam, Tara; Antonios, Joseph K.; Bushong, Eric A.; Koo, Edward H.; Ellisman, Mark H.; Ghosh, Anirvan

2014-01-01

The earliest stages of Alzheimer's disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease. PMID:24454724

Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

Directory of Open Access Journals (Sweden)

Richard eMiles

2014-01-01

Full Text Available In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No. Their physiological properties were explored to understand epileptiform discharges generated in the region. Synapses between pairs of pyramidal cells involve one or few release sites and are weaker than connections made by mossy fibres on CA3 pyramidal cells. Synapses with interneurons are rather effective, as needed to control unchecked excitation. We examine contributions of recurrent synapses to epileptiform synchrony, to the genesis of sharp waves in the CA3 region and to population oscillations at theta and gamma frequencies. Recurrent connections in CA3, as other associative cortices, have a lower connectivity spread over a larger area than in primary sensory cortices. This sparse, but wide-ranging connectivity serves the functions of an associative network, including acquisition of neuronal representations as activity in groups of CA3 cells and completion involving the recall from partial cues of these ensemble firing patterns.

Cloning and characterization of chitinases from interior spruce and lodgepole pine.

Science.gov (United States)

Kolosova, N; Breuil, C; Bohlmann, J

2014-05-01

Chitinases have been implicated in the defence of conifers against insects and pathogens. cDNA for six chitinases were cloned from interior spruce (Picea glauca x engelmannii) and four from lodgepole pine (Pinus contorta). The cloned interior spruce chitinases were annotated class I PgeChia1-1 and PgeChia1-2, class II PgeChia2-1, class IV PgeChia4-1, and class VII PgeChia7-1 and PgeChia7-2; lodgepole pine chitinases were annotated class I PcChia1-1, class IV PcChia4-1, and class VII PcChia7-1 and PcChia7-2. Chitinases were expressed in Escherichia coli with maltose-binding-protein tags and soluble proteins purified. Functional characterization demonstrated chitinolytic activity for the three class I chitinases PgeChia1-1, PgeChia1-2 and PcChia1-1. Transcript analysis established strong induction of most of the tested chitinases, including all three class I chitinases, in interior spruce and lodgepole pine in response to inoculation with bark beetle associated fungi (Leptographium abietinum and Grosmannia clavigera) and in interior spruce in response to weevil (Pissodes strobi) feeding. Evidence of chitinolytic activity and inducibility by fungal and insect attack support the involvement of these chitinases in conifer defense. Copyright © 2014 Elsevier Ltd. All rights reserved.

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

Science.gov (United States)

Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

2018-03-07

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Total regional and global number of synapses in the human brain neocortex

NARCIS (Netherlands)

Tang, Y.; Nyengaard, J.R.; Groot, D.M.G. de; Jorgen, H.; Gundersen, G.

2001-01-01

An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region

Enhanced long term microcircuit plasticity in the valproic acid animal model of autism

OpenAIRE

Guilherme T Silva; Guilherme T Silva; Jean-Vincent Le Bé; Imad Riachi; Tania Rinaldi; Kamila Markram; Henry Markram

2009-01-01

A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a mini-column (<50μm). In the present study, we explored whether Long Term Microcircuit ...

A review of evidence for GABergic predominance/glutamatergic deficit as a common etiological factor in both schizophrenia and affective psychoses: more support for a continuum hypothesis of "functional" psychosis.

Science.gov (United States)

Squires, R F; Saederup, E

1991-10-01

Virtually all antidepressant and antipsychotic drugs, including clozapine, rimcazole and lithium ion, are proconvulsants, and convulsive therapy, using metrazol, a known GABA-A antagonist, as well as electro-convulsive therapy, can be effective in treating both schizophrenia and affective psychoses. Many antidepressant and antipsychotic drugs, including clozapine, as well as some of their metabolites, reverse the inhibitory effect of GABA on 35S-TBPS binding, a reliable predictor of GABA-A receptor blockade. A review of relevant literature suggests that 1) "functional" psychoses constitute a continuum of disorders ranging from schizophrenia to affective psychoses with overlap of symptoms, heredity and treatments, 2) a weakening of GABergic inhibitory activity, or potentiation of counterbalancing glutamatergic neurotransmission, in the brain, may be involved in the therapeutic activities of both antidepressant and antipsychotic drugs, and 3) schizophrenia and the affective psychoses may be different expressions of the same underlying defect: GABergic preponderance/glutamatergic deficit. Schizophrenia and affective psychoses share the following: 1) several treatments are effective in both, 2) similar modes of inheritance, 3) congruent seasonal birth excesses, 4) enlarged cerebral ventricles and cerebellar vermian atrophy, 5) dexamethasone non-suppression. Both genetic and environmental factors are involved in both schizophrenia and affective psychoses, and several lines of evidence suggest that important environmental factors are neurotropic pathogens that selectively destroy glutamatergic neurons. One group of genes associated with psychoses may increase vulnerability to attack and destruction, by neurotropic pathogens, of excitatory glutamatergic neurons that counterbalance inhibitory GABergic neurons. A second group of genes may encode subunits of overactive GABA-A receptors, while a third group of genes may encode subunits of hypo-active glutamate receptors

An explorative study of the ecological design of residence architecture in Ming and Qing dynasties in Yangzhou

Directory of Open Access Journals (Sweden)

Lu Man

2017-01-01

Full Text Available Presently ecologicalization has become a key aspect of architecture designs. As studies deepen, the bountiful ecological ideas and design methods represented in Chinese traditional architectural culture are increasingly valued. There remain as of today quite a few residence mansions built in Ming and Qing dynasties in Yangzhou-a city famous for its history and culture. The distinctive regional culture and architectural style that those architectures embody has received worldwide attention in the academic field. By weighing on the shaping of architectural forms, choice in connection genres and structuring measures as well as sorting through and studying on the ecologicalized architectural design practices such as reemploying local materials, deeper understanding of traditional architecture will be achieved for us to better inherit and develop traditional architectural culture. Hence in-depth studies on contemporary ecological architecture and sustainable development will be of greater practical significance. Furthermore, it is beneficial to expand ideas on ecological design, truly integrate architectures into the setting to give expression to the ecological and culture features of them and provide theoretic support for creating new architecture with diversified culture implications and ecological features in light of actual conditions in an orderly manner.

The Scaffolding Protein Synapse-Associated Protein 97 is Required for Enhanced Signaling Through Isotype-Switched IgG Memory B Cell Receptors

Science.gov (United States)

Liu, Wanli; Chen, Elizabeth; Zhao, Xing Wang; Wan, Zheng Peng; Gao, Yi Ren; Davey, Angel; Huang, Eric; Zhang, Lijia; Crocetti, Jillian; Sandoval, Gabriel; Joyce, M. Gordon; Miceli, Carrie; Lukszo, Jan; Aravind, L.; Swat, Wojciech; Brzostowski, Joseph; Pierce, Susan K.

2012-01-01

Memory B cells are generated during an individual's first encounter with a foreign antigen and respond to re-encounter with the same antigen through cell surface immunoglobulin G (IgG) B cell receptors (BCRs) resulting in rapid, high-titered IgG antibody responses. Despite a central role for IgG BCRs in B cell memory, our understanding of the molecular mechanism by which IgG BCRs enhance antibody responses is incomplete. Here, we showed that the conserved cytoplasmic tail of the IgG BCR, which contains a putative PDZ-binding motif, associated with synapse-associated protein 97 (SAP97), a member of the PDZ domain–containing, membrane-associated guanylate-kinase family of scaffolding molecules that play key roles in controlling receptor density and signal strength at neuronal synapses. We showed that SAP97 accumulated and bound to IgG BCRs in the immune synapses that formed in response to engagement of the B cell with antigen. Knocking down SAP97 in IgG-expressing B cells or mutating the putative PDZ-binding motif in the tail impaired immune synapse formation, the initiation of IgG BCR signaling, and downstream activation of p38 mitogen-activated protein kinase. Thus, heightened B cell memory responses are encoded, in part, by a mechanism that involves SAP97 serving as a scaffolding protein in the IgG BCR immune synapse. PMID:22855505

Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation.

Science.gov (United States)

Hu, Jiangyuan; Schacher, Samuel

2015-12-09

Synapses express different forms of plasticity that contribute to different forms of memory, and both memory and plasticity can become labile after reactivation. We previously reported that a persistent form of nonassociative long-term facilitation (PNA-LTF) of the sensorimotor synapses in Aplysia californica, a cellular analog of long-term sensitization, became labile with short-term heterosynaptic reactivation and reversed when the reactivation was followed by incubation with the protein synthesis inhibitor rapamycin. Here we examined the reciprocal impact of different forms of short-term plasticity (reactivations) on a persistent form of associative long-term facilitation (PA-LTF), a cellular analog of classical conditioning, which was expressed at Aplysia sensorimotor synapses when a tetanic stimulation of the sensory neurons was paired with a brief application of serotonin on 2 consecutive days. The expression of short-term homosynaptic plasticity [post-tetanic potentiation or homosynaptic depression (HSD)], or short-term heterosynaptic plasticity [serotonin-induced facilitation or neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa)-induced depression], at synapses expressing PA-LTF did not affect the maintenance of PA-LTF. The kinetics of HSD was attenuated at synapses expressing PA-LTF, which required activation of protein kinase C (PKC). Both PA-LTF and the attenuated kinetics of HSD were reversed by either a transient blockade of PKC activity or a homosynaptic, but not heterosynaptic, reactivation when paired with rapamycin. These results indicate that two different forms of persistent synaptic plasticity, PA-LTF and PNA-LTF, expressed at the same synapse become labile when reactivated by different stimuli. Activity-dependent changes in neural circuits mediate long-term memories. Some forms of long-term memories become labile and can be reversed with specific types of reactivations, but the mechanism is complex. At the cellular level, reactivations that induce a

Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

Science.gov (United States)

Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2006-10-01

Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

Unsupervised learning in neural networks with short range synapses

Science.gov (United States)

Brunnet, L. G.; Agnes, E. J.; Mizusaki, B. E. P.; Erichsen, R., Jr.

2013-01-01

Different areas of the brain are involved in specific aspects of the information being processed both in learning and in memory formation. For example, the hippocampus is important in the consolidation of information from short-term memory to long-term memory, while emotional memory seems to be dealt by the amygdala. On the microscopic scale the underlying structures in these areas differ in the kind of neurons involved, in their connectivity, or in their clustering degree but, at this level, learning and memory are attributed to neuronal synapses mediated by longterm potentiation and long-term depression. In this work we explore the properties of a short range synaptic connection network, a nearest neighbor lattice composed mostly by excitatory neurons and a fraction of inhibitory ones. The mechanism of synaptic modification responsible for the emergence of memory is Spike-Timing-Dependent Plasticity (STDP), a Hebbian-like rule, where potentiation/depression is acquired when causal/non-causal spikes happen in a synapse involving two neurons. The system is intended to store and recognize memories associated to spatial external inputs presented as simple geometrical forms. The synaptic modifications are continuously applied to excitatory connections, including a homeostasis rule and STDP. In this work we explore the different scenarios under which a network with short range connections can accomplish the task of storing and recognizing simple connected patterns.

Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.

Science.gov (United States)

Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T; Wangsawihardja, Felix; Ricci, Anthony J; Mustapha, Mirna

2016-01-01

Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1(dw)) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1(dw) mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1(dw) IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1(dw) IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1(dw) IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity

Directory of Open Access Journals (Sweden)

Akiko Ueno

2018-03-01

Full Text Available Summary: In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. : Ueno et al. finds that Lrit1 plays an important role in regulating the synaptic connection between cone photoreceptors and cone ON-bipolar cells. The Frmpd2-Lrit1-mGluR6 axis is crucial for selective synapse formation in cone photoreceptors and for development of normal visual function. Keywords: retina, circuit, synapse formation, cone photoreceptor cell, ON-bipolar cell, visual acuity

Accelerated Intoxication of GABAergic Synapses by Botulinum Neurotoxin A Disinhibits Stem Cell-Derived Neuron Networks Prior to Network Silencing

Science.gov (United States)

2015-04-23

administered BoNT can lead to central nervous system intoxication is currently being debated. Recent findings in vitro and in vivo suggest that BoNT...Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A disinhibits 5a...April 2015 Published: 23 April 2015 Citation: Beske PH, Scheeler SM, AdlerM and McNutt PM (2015) Accelerated intoxication of GABAergic synapses by

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

DEFF Research Database (Denmark)

Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano

2018-01-01

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report...... pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling...... the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation....

Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder.

Science.gov (United States)

Kim, Ki Chan; Kim, Pitna; Go, Hyo Sang; Choi, Chang Soon; Park, Jin Hee; Kim, Hee Jin; Jeon, Se Jin; Dela Pena, Ike Campomayor; Han, Seol-Heui; Cheong, Jae Hoon; Ryu, Jong Hoon; Shin, Chan Young

2013-03-01

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by three main behavioral symptoms including social deficits, impaired communication, and stereotyped and repetitive behaviors. ASD prevalence shows gender bias to male. Prenatal exposure to valproic acid (VPA), a drug used in epilepsy and bipolar disorder, induces autistic symptoms in both human and rodents. As we reported previously, prenatally VPA-exposed animals at E12 showed impairment in social behavior without any overt reproductive toxicity. Social interactions were not significantly different between male and female rats in control condition. However, VPA-exposed male offspring showed significantly impaired social interaction while female offspring showed only marginal deficits in social interaction. Similar male inclination was observed in hyperactivity behavior induced by VPA. In addition to the ASD-like behavioral phenotype, prenatally VPA-exposed rat offspring shows crooked tail phenotype, which was not different between male and female groups. Both male and female rat showed reduced GABAergic neuronal marker GAD and increased glutamatergic neuronal marker vGluT1 expression. Interestingly, despite of the similar increased expression of vGluT1, post-synaptic marker proteins such as PSD-95 and α-CAMKII expression was significantly elevated only in male offspring. Electron microscopy showed increased number of post-synapse in male but not in female at 4 weeks of age. These results might suggest that the altered glutamatergic neuronal differentiation leads to deranged post-synaptic maturation only in male offspring prenatally exposed to VPA. Consistent with the increased post-synaptic compartment, VPA-exposed male rats showed higher sensitivity to electric shock than VPA-exposed female rats. These results suggest that prenatally VPA-exposed rats show the male preponderance of ASD-like behaviors including defective social interaction similar to human autistic patients, which

Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.

Science.gov (United States)

Schneider, Patrick; Petzold, Sandra; Sommer, Angela; Nitsch, Robert; Schwegler, Herbert; Vogt, Johannes; Roskoden, Thomas

2018-01-15

Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1 -/- ) mice and PRG-1/LPA 2 -receptor double knockout (PRG-1 -/- /LPA 2 -/- ) mice in two open field settings of different size and assessing motor behavior in the Rota Rod test. PRG-1 -/- mice displayed significantly longer path lengths and higher running speed in both open field conditions. In addition, PRG-1 -/- mice spent significantly longer time in the larger open field and displayed rearing and self-grooming behavior. Furthermore PRG-1 -/- mice displayed stereotypical behavior resembling phenotypes of psychiatric disorders in the smaller sized open field arena. Altogether, this behavior is similar to the stereotypical behavior observed in animal models for psychiatric disease of autistic spectrum disorders which reflects a disrupted balance between glutamatergic and GABAergic synapses. These differences indicate an altered excitation/inhibition balance in neuronal circuits in PRG-1 -/- mice as recently shown in the somatosensory cortex [38]. In contrast, PRG-1 -/- /LPA 2 -/- did not show significant changes in behavior in the open field suggesting that these specific alterations were abolished when the LPA 2 -receptor was lacking. Our findings indicate that PRG-1 deficiency led to over-excitability caused by an altered LPA/LPA 2 -R signaling inducing a behavioral phenotype typically observed in animal models for psychiatric disorders. Copyright �

Diversity in immunological synapse structure

Science.gov (United States)

Thauland, Timothy J; Parker, David C

2010-01-01

Immunological synapses (ISs) are formed at the T cell–antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non-classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non-classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T-cell function. PMID:21039474

The demise of the synapse as the locus of memory: A looming paradigm shift?