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Sample records for regions including hippocampus

  1. Diffusion-weighted imaging in transient global amnesia exposes the CA1 region of the hippocampus

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    Lee, Ho Yun; Kim, Jae Hyoung; Weon, Young-Cheol; Youn, Sung Won; Kim, Sung Hyun [Seoul National University Bundang Hospital, Department of Radiology, Seoul National University College of Medicine, Seongnam-si (Korea); Lee, Jung Seok; Kim, Sang Yun [Seoul National University Bundang Hospital, Department of Neurology, Seoul National University College of Medicine, Seongnam-si (Korea)

    2007-06-15

    Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia without alteration of consciousness or personal identity. Interestingly, recent studies have reported a high frequency of small high-signal abnormalities in the hippocampus with diffusion-weighted (DW) imaging, and ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, known to be susceptible to ischemia. Over a 30-month period 34 patients with TGA underwent MRI including DW imaging within 4 days of symptom onset. Patients with high-signal abnormalities in the hippocampus on the initial DW images underwent subsequent DW and T2-weighted imaging in the coronal plane to identify the precise lesion locations. Fourteen patients had small (1-3 mm) high-signal abnormalities in the hippocampus unilaterally on DW images. One of these patients had two lesions in one hippocampus and therefore in total 15 lesions were identified: four in the hippocampal head, and 11 in the body. Eleven lesions in ten patients with available coronal images were clearly demonstrated on both coronal DW and T2-weighted images and were localized to the lateral portion of the hippocampus, corresponding to the CA1 region. Lesions associated with TGA were localized exclusively to the lateral portion of the hippocampus corresponding to the CA1 region. This finding supports the ischemic etiology of TGA; however, the pathophysiological mechanism involved requires further study. (orig.)

  2. Diffusion-weighted imaging in transient global amnesia exposes the CA1 region of the hippocampus

    International Nuclear Information System (INIS)

    Lee, Ho Yun; Kim, Jae Hyoung; Weon, Young-Cheol; Youn, Sung Won; Kim, Sung Hyun; Lee, Jung Seok; Kim, Sang Yun

    2007-01-01

    Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia without alteration of consciousness or personal identity. Interestingly, recent studies have reported a high frequency of small high-signal abnormalities in the hippocampus with diffusion-weighted (DW) imaging, and ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, known to be susceptible to ischemia. Over a 30-month period 34 patients with TGA underwent MRI including DW imaging within 4 days of symptom onset. Patients with high-signal abnormalities in the hippocampus on the initial DW images underwent subsequent DW and T2-weighted imaging in the coronal plane to identify the precise lesion locations. Fourteen patients had small (1-3 mm) high-signal abnormalities in the hippocampus unilaterally on DW images. One of these patients had two lesions in one hippocampus and therefore in total 15 lesions were identified: four in the hippocampal head, and 11 in the body. Eleven lesions in ten patients with available coronal images were clearly demonstrated on both coronal DW and T2-weighted images and were localized to the lateral portion of the hippocampus, corresponding to the CA1 region. Lesions associated with TGA were localized exclusively to the lateral portion of the hippocampus corresponding to the CA1 region. This finding supports the ischemic etiology of TGA; however, the pathophysiological mechanism involved requires further study. (orig.)

  3. Combined histochemical staining, RNA amplification, regional, and single cell cDNA analysis within the hippocampus.

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    Ginsberg, Stephen D; Che, Shaoli

    2004-08-01

    The use of five histochemical stains (cresyl violet, thionin, hematoxylin & eosin, silver stain, and acridine orange) was evaluated in combination with an expression profiling paradigm that included regional and single cell analyses within the hippocampus of post-mortem human brains and adult mice. Adjacent serial sections of human and mouse hippocampus were labeled by histochemistry or neurofilament immunocytochemistry. These tissue sections were used as starting material for regional and single cell microdissection followed by a newly developed RNA amplification procedure (terminal continuation (TC) RNA amplification) and subsequent hybridization to custom-designed cDNA arrays. Results indicated equivalent levels of global hybridization signal intensity and relative expression levels for individual genes for hippocampi stained by cresyl violet, thionin, and hematoxylin & eosin, and neurofilament immunocytochemistry. Moreover, no significant differences existed between the Nissl stains and neurofilament immunocytochemistry for individual CA1 neurons obtained via laser capture microdissection. In contrast, a marked decrement was observed in adjacent hippocampal sections stained for silver stain and acridine orange, both at the level of the regional dissection and at the CA1 neuron population level. Observations made on the cDNA array platform were validated by real-time qPCR using primers directed against beta-actin and glyceraldehyde-3 phosphate dehydrogenase. Thus, this report demonstrated the utility of using specific Nissl stains, but not stains that bind RNA species directly, in both human and mouse brain tissues at the regional and cellular level for state-of-the-art molecular fingerprinting studies.

  4. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

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    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  5. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

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    Olga M. Pulido

    2008-02-01

    Full Text Available Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk, and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity

  6. Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

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    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.

  7. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

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    Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

    2016-12-07

    Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3.

    LENUS (Irish Health Repository)

    2011-05-01

    The hippocampus is strongly implicated in schizophrenia and, to a lesser degree, bipolar disorder. Proteomic investigations of the different regions of the hippocampus may help us to clarify the basis and the disease specificity of the changes.

  9. INFLUENCE OF ELECTROACUPUNCTURE ON THE ULTRASTRUCTURE OF CA3 REGION OF THE HIPPOCAMPUS IN VD RATS

    Institute of Scientific and Technical Information of China (English)

    YAN Bing; XU Neng-gui; HE Li-lei; TANG Chun-zhi; SHAO Ying

    2006-01-01

    Objective: To observe the effect of electroacupuncture (EA) on learning and memory abilities and ultrastructure of synapses in CA3 region of the hippocampus in vascular dementia (VD) rats. Methods: A total of 32 SD rats were randomized into control (sham-operation, n = 7), model (n = 7), EA (n = 9) and medication (n=9) groups. VD model was established by occlusion of the bilateral vertebral arteries (electrocoagulation) and bilateral common carotid arteries (occlusion for 5 min and reperfusion for 10 min, repeated the procedure for 3 times to induce global ischemia). EA (150 Hz, 1 mA) was applied to "Baihui"(百会GV 20), "Geshu"(膈俞 BL 17), "Pishu"(脾俞 BL 20) and "Shenshu"(肾俞 BL 23) for 20 min, once daily and continuously for 15 days. In medication group, the rats were fed with Nimotong (12 mg/kg), once daily and continuously for 15 days. Morris water maze method was used to test the animals' learning and memory abilities (latencies to find the hidden platform determined by place navigation trials, and latencies to cross on the location of the removed platform determined by spatial probe trials) after the treatment. Ultrastructural changes (numerical density, NA,surface density, Sv and volume density, Vv) of Gray type 1 synapses in CA3 region of the hippocampus were observed by using transmission electronic microscope and automatic image analysis system. Results: 1 ) Place navigation test showed that in comparison with control group, the average escape latency of VD group was significantly longer (P<0.01), while in comparison with VD group, the latencies of both EA and medication groups decreased significantly ( P<0.01 ). No significant difference was found between EA and medication groups in the escape latency (P>0.05). 2) Spatial probe-test displayed that in comparison with control group, the times which the animals crossed the target platform in VD group decreased significantly (P<0.01), while compared with VD group, those of both EA and

  10. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

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    Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

    2014-01-01

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in

  11. A signature of attractor dynamics in the CA3 region of the hippocampus.

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    César Rennó-Costa

    2014-05-01

    Full Text Available The notion of attractor networks is the leading hypothesis for how associative memories are stored and recalled. A defining anatomical feature of such networks is excitatory recurrent connections. These "attract" the firing pattern of the network to a stored pattern, even when the external input is incomplete (pattern completion. The CA3 region of the hippocampus has been postulated to be such an attractor network; however, the experimental evidence has been ambiguous, leading to the suggestion that CA3 is not an attractor network. In order to resolve this controversy and to better understand how CA3 functions, we simulated CA3 and its input structures. In our simulation, we could reproduce critical experimental results and establish the criteria for identifying attractor properties. Notably, under conditions in which there is continuous input, the output should be "attracted" to a stored pattern. However, contrary to previous expectations, as a pattern is gradually "morphed" from one stored pattern to another, a sharp transition between output patterns is not expected. The observed firing patterns of CA3 meet these criteria and can be quantitatively accounted for by our model. Notably, as morphing proceeds, the activity pattern in the dentate gyrus changes; in contrast, the activity pattern in the downstream CA3 network is attracted to a stored pattern and thus undergoes little change. We furthermore show that other aspects of the observed firing patterns can be explained by learning that occurs during behavioral testing. The CA3 thus displays both the learning and recall signatures of an attractor network. These observations, taken together with existing anatomical and behavioral evidence, make the strong case that CA3 constructs associative memories based on attractor dynamics.

  12. Transient cerebral ischemia induces albumin expression in microglia only in the CA1 region of the gerbil hippocampus.

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    Park, Joon Ha; Park, Jin-A; Ahn, Ji Hyeon; Kim, Yang Hee; Kang, Il Jun; Won, Moo-Ho; Lee, Choong-Hyun

    2017-07-01

    Albumin, the most abundant plasma protein, is known to exhibit a neuroprotective effect in animal models of focal and global cerebral ischemia. In the present study, the expression and immunoreactivity of albumin was examined in the hippocampus following 5 min of transient cerebral ischemia in gerbils. Albumin immunoreactivity was observed in microglia of the CA1 hippocampal region 2 days post‑ischemic insult, and it was significantly increased at 4 days following ischemia-reperfusion. In addition, at 4 days post‑ischemic insult, albumin‑immunoreactive microglia were abundant in the stratum pyramidale of the CA1 region. The present results demonstrated that albumin was newly expressed post‑injury in microglia in the CA1 region, suggesting ischemia‑induced neuronal loss. Albumin expression may therefore be associated with ischemia‑induced delayed neuronal death in the CA1 region following transient cerebral ischemia.

  13. Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.

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    Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

    2006-10-17

    The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively.

  14. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

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    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  15. Regional Fluid-Attenuated Inversion Recovery (FLAIR at 7 Tesla correlates with Amyloid beta in Hippocampus and Brainstem of cognitively normal elderly subjects.

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    Simon J Schreiner

    2014-09-01

    Full Text Available Background: Accumulation of amyloid beta (Aβ may occur during healthy aging and is a risk factor for Alzheimer Disease (AD. While individual Aβ-accumulation can be measured non-invasively using Pittsburgh compound-B positron-emission-tomography (PiB-PET, Fluid-Attenuated Inversion Recovery (FLAIR is a Magnetic Resonance Imaging (MRI sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR- intensity. Methods: 14 healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T. Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho, followed by Holm-Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right:rho=0.86; left:rho=0.84, Brainstem (rho=0.85 and left Basal Ganglia vessel region (rho=0.82. Conclusions: Our finding of a significant relationship between PiB- and FLAIR-intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative

  16. Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

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    Schreiner, Simon J.; Liu, Xinyang; Gietl, Anton F.; Wyss, Michael; Steininger, Stefanie C.; Gruber, Esmeralda; Treyer, Valerie; Meier, Irene B.; Kälin, Andrea M.; Leh, Sandra E.; Buck, Alfred; Nitsch, Roger M.; Pruessmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

    2014-01-01

    Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative

  17. Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

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    Alquicer, Glenda; Silva-Gómez, Adriana B; Peralta, Fernando; Flores, Gonzalo

    2004-04-01

    The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

  18. Hippocampus at 25

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    Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

    2017-01-01

    The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

  19. Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat.

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    Amegandjin, Clara A; Jammow, Wafaa; Laforest, Sylvie; Riad, Mustapha; Baharnoori, Moogeh; Badeaux, Frédérique; DesGroseillers, Luc; Murai, Keith K; Pasquale, Elena B; Drolet, Guy; Doucet, Guy

    2016-08-15

    EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface-expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ∼3-5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ∼10-40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462-2478, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

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    Kay, A R; Wong, R K

    1987-11-01

    1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

  1. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

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    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  2. The hippocampus - pictorial essay

    International Nuclear Information System (INIS)

    Whan, A.; Mitchell, L.A.

    2002-01-01

    Full text: We aim to demonstrate the anatomy and pathology of the hippocampus. It is important that radiologists distinguish normal and abnormal hippocampal hippocampal MR appearances, since hippocampal sclerosis is the commonest cause of surgically treatable temporal lobe epilepsy. The detailed anatomy of the hippocampus is reviewed and correlated with normal MR appearances. Our radiology database was reviewed to determine both common and unusual pathologies affecting the hippocampus. Most scans were performed for our large Comprehensive Epilepsy Program, for investigation of epilepsy of possible seizures. Less frequent indications included memory loss (acute or chronic), stroke, headache, and altered conscious state. Hippocampal sclerosis was the commonest MR abnormality. This was occasionally bilateral or associated with other pathology. Other common findings included mild hippocampal asymmetry, bilateral atrophy, or normal variants such as choroid fissure cysts. Other pathologies included cortical developmental malformations, infarction, posttraumatic gliosis, herpes, simplex encephalitis, paraneoplastic limbic encephalitis, vascular malformations, sarcoidosis, benign tumours such as gangliogliomas and dysembyoplastic neuroepithelial tumours (DNET) and malignant tumours. The hippocampus has a complex anatomy visible on high resolution MRI. In the clinical context of epilepsy, hippocampal sclerosis is an important pathology, but a range of conditions may affect the hippocampus, readily demonstrated by MRI. Copyright (2002) Blackwell Science Pty Ltd

  3. Regional Metabolic Changes in the Hippocampus and Posterior Cingulate Area Detected with 3-Tesla Magnetic Resonance Spectroscopy in Patients with Mild Cognitive Impairment and Alzheimer Disease

    International Nuclear Information System (INIS)

    Zhiqun Wang; Cheng Zhao; Kuncheng Li; Lei Yu; Weidong Zhou

    2009-01-01

    Background: Magnetic resonance spectroscopy (MRS) plays an important role in early diagnosis of Alzheimer disease (AD). There are many reports on MRS studies among individuals with AD and mild cognitive impairment (MCI). However, very few studies have compared spectroscopic data of different limbic regions among AD and MCI subjects. Purpose: To compare metabolite changes of different regions in the brain of AD and MCI patients by using 3.0T short-echo-time MRS. Material and Methods: Metabolite ratios in the hippocampus and posterior cingulate area were compared in a group of patients with AD (n=16), MCI (n=16), and normal subjects as a control group (n=16). Clinical neuropsychological tests were measured in all subjects. Results: In the hippocampus, there were significant differences in N-acetylaspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr, and mI/NAA ratios among the three groups. However, there were no significant differences in choline (Cho)/Cr ratio among the three groups. In the posterior cingulate area, there were no significant differences in the NAA/Cr, Cho/Cr, and mI/Cr ratios among the three groups. However, there were significant differences in mI/NAA ratio between patients with AD and the control group, and between the AD and MCI groups. In addition, there was significant correlation between mI/NAA ratio and Mini Mental Status Exam (MMSE) score in subjects with AD and MCI. Conclusion: The study reveals that the elevation of mI/NAA ratio in the hippocampus is more significant than that in the posterior cingulate area, which corresponds to the pathologic procession of AD. The ratios of mI/NAA in the hippocampus and in the posterior cingulate area together provide valuable discrimination among the three groups (AD, MCI, and controls). There is a significant correlation between mI/NAA ratio and cognitive decline

  4. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  5. One-trial memory for object-place associations after separate lesions of hippocampus and posterior parahippocampal region in the monkey.

    Science.gov (United States)

    Malkova, Ludise; Mishkin, Mortimer

    2003-03-01

    In earlier studies of one-trial spatial memory in monkeys (Parkinson et al., 1988; Angeli et al., 1993), severe and chronic memory impairment for both object-place association and place alone was found after ablation of the hippocampal formation. The results appeared to provide the first clear-cut evidence in the monkey of the essential role of the hippocampus in spatial memory, but that interpretation neglected the inclusion in the lesion of the underlying posterior parahippocampal region. To determine the separate contributions of the hippocampus and posterior parahippocampal region to these spatial forms of one-trial memory, we trained 10 rhesus monkeys, as before, to remember the spatial positions of either two different trial-unique objects overlying two of the wells in a three-well test tray (object-place trials) or simply two of the three wells (place trials). Six of the monkeys then received ibotenic acid lesions restricted to the hippocampal formation (group H), and the four others received selective ablations of the posterior parahippocampal region (group P), comprising mainly parahippocampal cortex, parasubiculum, and presubiculum. Group H was found to be completely unaffected postoperatively on both types of trials, whereas group P sustained an impairment on both types equal in magnitude to that observed after the combined lesions in the original studies. Thus, contrary to the previous interpretation, one-trial memory for object-place association and, perhaps more fundamentally, one-trial memory for two different places appear to be critically dependent not on the hippocampal formation but rather on the posterior parahippocampal region.

  6. Effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of hippocampus of rats after sleep deprivation

    Directory of Open Access Journals (Sweden)

    Jiang-hua SI

    2014-04-01

    Full Text Available Objective To investigate the effects of high-altitude environment on cognitive function and ultrastructure in CA1 region of the hippocampus of Wistar rats in sleep deprivation (SD.  Methods SD was induced in Wistar rats by employing "flower pot" technique. Sixty-four rats were randomly divided into 2 groups: Lanzhou group (at an altitude of 1520 m and Kekexili group (at an altitude of 4767 m, and each group was further divided into 4 subgroups according to the time of SD (0, 1, 3 and 5 d. The behaviors of rats were studied by Morris water maze test at given time points. The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM.  Results 1 Compared with Lanzhou group, rat behavior of Kekexili group presented excitement-irritation-suppression changes with the extension of SD time, but the extent was weakened gradually, and time of sleepiness increased obviously. 2 Compared with Lanzhou group, neurons in CA1 region of hippocampus showed enlarged cell body, disappeared nuclear membrane, shrunken nuclei and decreased organelle. End-feet of glia cells sticking to capillaries swelled and ruptured, and the typical synaptic structure disappeared. 3 Morris water maze test: as compared with Lanzhou group, the escape latency of Kekexili group prolonged (P < 0.05, for all, the ability of distance exploration increased (P < 0.05, for all, and the times across plot decreased (P < 0.05, for all in 1, 3 and 5 d of SD.  Conclusions High-altitude environment may significantly influence the cognitive function of rats in SD, and there was close correlation between the cognitive disorders and the changes in the ultrastructure of hippocampal CA1 region. doi: 10.3969/j.issn.1672-6731.2014.04.012

  7. Vertical distribution of the seahorse Hippocampus reidi Ginsburg, 1933 in the Arraial do Cabo region, Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Viviane Martins de Oliveira

    2012-06-01

    Full Text Available Seahorses are found all over the world, in tropical and temperate coastal waters. The main aim of this study was to characterize the Hippocampus reidi populations in different depth and hydrodynamism categories in Arraial do Cabo, Rio de Janeiro state. The study was developed through scuba diving, with transects of 20m x 5m in two different depth layers: shallow, between 0 and 5m, and deep, between 5 and 10m. Through visual surveys, individuals were identified according to species, sex, and size (height – HT. The density of H. reidi varied according to depth and hydrodynamism. The highest mean depth was found in the Cabo Frio Island – Ponta do Anequin, as the lowest depth was found in Praia do Forno – Ponta D’água. There is no significant difference in the size of individuals nor in the sex ratio between the depth categories. The sex ratio of H. reidi in the population of Arraial do Cabo was 1:1. The results obtained indicated that the population characteristics are similar between the two depth layers.

  8. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study

    International Nuclear Information System (INIS)

    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H.; Mori, K.

    1999-01-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  9. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, H; Harada, M; Hisaoka, S; Nishitani, H [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  10. Evolution of the hippocampus in reptiles and birds.

    Science.gov (United States)

    Striedter, Georg F

    2016-02-15

    Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions. © 2015 Wiley Periodicals, Inc.

  11. Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

    Directory of Open Access Journals (Sweden)

    Meyerhoff James L

    2011-07-01

    Full Text Available Abstract Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus. Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There

  12. Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

    Science.gov (United States)

    Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

    2017-01-01

    The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

  13. Emission-line diagnostics of nearby H II regions including interacting binary populations

    Science.gov (United States)

    Xiao, Lin; Stanway, Elizabeth R.; Eldridge, J. J.

    2018-06-01

    We present numerical models of the nebular emission from H II regions around young stellar populations over a range of compositions and ages. The synthetic stellar populations include both single stars and interacting binary stars. We compare these models to the observed emission lines of 254 H II regions of 13 nearby spiral galaxies and 21 dwarf galaxies drawn from archival data. The models are created using the combination of the BPASS (Binary Population and Spectral Synthesis) code with the photoionization code CLOUDY to study the differences caused by the inclusion of interacting binary stars in the stellar population. We obtain agreement with the observed emission line ratios from the nearby star-forming regions and discuss the effect of binary-star evolution pathways on the nebular ionization of H II regions. We find that at population ages above 10 Myr, single-star models rapidly decrease in flux and ionization strength, while binary-star models still produce strong flux and high [O III]/H β ratios. Our models can reproduce the metallicity of H II regions from spiral galaxies, but we find higher metallicities than previously estimated for the H II regions from dwarf galaxies. Comparing the equivalent width of H β emission between models and observations, we find that accounting for ionizing photon leakage can affect age estimates for H II regions. When it is included, the typical age derived for H II regions is 5 Myr from single-star models, and up to 10 Myr with binary-star models. This is due to the existence of binary-star evolution pathways, which produce more hot Wolf-Rayet and helium stars at older ages. For future reference, we calculate new BPASS binary maximal starburst lines as a function of metallicity, and for the total model population, and present these in Appendix A.

  14. Environmental radioactivity in the North Atlantic region. The Faroe Islands and Greenland included. 1985

    International Nuclear Information System (INIS)

    Aarkrog, A.; Boelskifte, S.; Dahlgaard, H.; Hansen, H.; Buch, E.; Christensen, G.C.; Hallstadius, L.; Rioseco, J.; Holm, E.

    1987-06-01

    Measurements of fallout radioactivity in the North Atlantic region including the Faroe Islands and Greenland are reported. Strontium-90 and cesium-137 was determined in samples of precipitation, sea water vegetation, various foodstuffs (including milk in the Faroes) and drinking water. Estimates are given of the mean contents of 90 Sr a 137 Cs in human diet in the Faroes and Greenland in 1985. Results from samplings of surface sea water and seaweed in the English Channel, the Fram Strait and along the Norwegian and Greenland coast are reported. Beside radiocesium and 90 Sr some of these samples have also been analysed for tritium, plutonium and americium. Finally technetium-99 data on seaweed and sea water samples collected in the North Atlantic region are presented. 14 refs. (author)

  15. Environmental radioactivity in the North Atlantic region. The Faroe Islands and Greenland included. 1983

    International Nuclear Information System (INIS)

    Aarkrog, A.; Boelskifte, S.; Buch, E.; Christensen, G.C.; Dahlgaard, H.; Hallstadius, L.; Hansen, H.; Holm, E.; Mattsson, S.; Meide, A.

    1984-12-01

    Measurements of fallout radioactivity in the North Atlantic region including the Faroe Islands and Greenland are reported. Strontium-90 and cesium-137 was determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes) and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1983. Results from samplings of surface sea water and seaweed in the Norwegian and Greenland Seas and along the Norwegian and Greenland west coasts are reported. Beside radiocesium and 90 Sr some of these samples have also been anlysed for tritium,plutonium and americium. Finally technetium-99 data on seaweed samples collected in the North Atlantic region since the beginning of the sixties are presented. (author)

  16. Environmental radioactivity in the North Atlantic region. The Faroe Islands and Greenland included. 1984

    International Nuclear Information System (INIS)

    Aarkrog, A.; Boelskifte, S.; Buch, E.; Christensen, G.C.; Dahlgaard, H.; Hallstadius, L.; Hansen, H.; Holm, E.

    1985-12-01

    Measurements of fallout radioactivity in the North Atlantic region including the Faroe Islands and Greenland are reported. Strontium-90 and cesium-137 was determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes) and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1984. Results from samplings of surface sea water and seaweed in the Norwegian and Greenland Seas and along the Norwegian and Greenland west coasts are reported. Beside radiocesium and 90 Sr some of these samples have also been anlysed for tritium, polonium, plutonium and americium. Finally technetium-99 data on seaweed samples collected in the North Atlantic region since the beginning of the sixties are presented. (author)

  17. Hippocampus discovery First steps

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available The first steps of the discovery, and the main discoverers, of the hippocampus are outlined. Arantius was the first to describe a structure he named "hippocampus" or "white silkworm". Despite numerous controversies and alternate designations, the term hippocampus has prevailed until this day as the most widely used term. Duvernoy provided an illustration of the hippocampus and surrounding structures, considered the first by most authors, which appeared more than one and a half century after Arantius' description. Some authors have identified other drawings and texts which they claim predate Duvernoy's depiction, in studies by Vesalius, Varolio, Willis, and Eustachio, albeit unconvincingly. Considering the definition of the hippocampal formation as comprising the hippocampus proper, dentate gyrus and subiculum, Arantius and Duvernoy apparently described the gross anatomy of this complex. The pioneering studies of Arantius and Duvernoy revealed a relatively small hidden formation that would become one of the most valued brain structures.

  18. Environmental radioactivity in the North Atlantic region including the Faroe Islands and Greenland. 1990 and 1991

    International Nuclear Information System (INIS)

    Aarkrog, A.; Chen, Q.J.; Dahlgaard, H.; Hansen, H.; Nielsen, S.P.; Strandberg, M.; Buch, E.; Christensen, G.C.; Holm, E.

    1994-01-01

    Measurements of fallout radioactivity in the North Atlantic region including Faroe Islands and Greenland are reported. Strontium-90, cesium-137 and cesium-134 were determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes), and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1990 and 1991. 99 Tc data on marine samples, in particular sea water from the Greenland Sea, are reported. (au) (77 tabs., 46 ills., 8 refs.)

  19. Environmental radioactivity in the North Atlantic region including the Faroe Islands and Greenland

    International Nuclear Information System (INIS)

    Aarkrog, A.; Chen, Q.J.; Dahlgaard, H.; Hansen, H.; Nielsen, S.P.; Buch, E.; Christensen, G.C.; Holm, E.

    1992-01-01

    Measurements of fallout radioactivity in the North Atlantic region including the Faroe Islands and Greenland are reported. Strontium-90, cesium-137 and cesium-134 were determined in samples of precipitation, sea water, vegetation, various foodstuffs (including milk in the Faroes), and drinking water. Estimates are given of the mean contents of 90 Sr and 137 Cs in human diet in the Faroes and Greenland in 1988 and 1989. 99 Tc data on marine samples, in particular sea water from the Greenland Sea, are reported. (au) (91 taps., 51 ills., 7 refs.)

  20. An ArcGIS approach to include tectonic structures in point data regionalization.

    Science.gov (United States)

    Darsow, Andreas; Schafmeister, Maria-Theresia; Hofmann, Thilo

    2009-01-01

    Point data derived from drilling logs must often be regionalized. However, aquifers may show discontinuous surface structures, such as the offset of an aquitard caused by tectonic faults. One main challenge has been to incorporate these structures into the regionalization process of point data. We combined ordinary kriging and inverse distance weighted (IDW) interpolation to account for neotectonic structures in the regionalization process. The study area chosen to test this approach is the largest porous aquifer in Austria. It consists of three basins formed by neotectonic events and delimited by steep faults with a vertical offset of the aquitard up to 70 m within very short distances. First, ordinary kriging was used to incorporate the characteristic spatial variability of the aquitard location by means of a variogram. The tectonic faults could be included into the regionalization process by using breaklines with buffer zones. All data points inside the buffer were deleted. Last, IDW was performed, resulting in an aquitard map representing the discontinuous surface structures. This approach enables one to account for such surfaces using the standard software package ArcGIS; therefore, it could be adopted in many practical applications.

  1. A novel large deletion of the ICR1 region including H19 and putative enhancer elements.

    Science.gov (United States)

    Fryssira, Helen; Amenta, Stella; Kanber, Deniz; Sofocleous, Christalena; Lykopoulou, Evangelia; Kanaka-Gantenbein, Christina; Cerrato, Flavia; Lüdecke, Hermann-Josef; Bens, Susanne; Riccio, Andrea; Buiting, Karin

    2015-05-06

    Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth disorder with a variable clinical phenotype caused by deregulation affecting imprinted genes in the chromosomal region 11p15. Alterations of the imprinting control region 1 (ICR1) at the IGF2/H19 locus resulting in biallelic expression of IGF2 and biallelic silencing of H19 account for approximately 10% of patients with BWS. The majority of these patients have epimutations of the ICR1 without detectable DNA sequence changes. Only a few patients were found to have deletions. Most of these deletions are small affecting different parts of the ICR1 differentially methylated region (ICR1-DMR) removing target sequences for CTCF. Only a very few deletions reported so far include the H19 gene in addition to the CTCF binding sites. None of these deletions include IGF2. A male patient was born with hypotonia, facial dysmorphisms and hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation-specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have identified a maternally inherited large deletion of the ICR1 region in a patient and his mother. The deletion results in a variable clinical expression with a classical BWS in the mother and a more severe presentation of BWS in her son. By genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA including the ICR1DMR, H19, two adjacent non-imprinted genes and two of three predicted enhancer elements downstream to H19. Methylation analysis by deep bisulfite next generation sequencing revealed hypermethylation of the maternal allele at the IGF2 locus in both, mother and child, although IGF2 is not affected by the deletion. We here report on a novel large familial deletion of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF binding cannot take place and the residual enhancer elements have access to the IGF2 promoters. The aberrant methylation (hypermethylation) of the maternal IGF2

  2. Association between income and the hippocampus.

    Directory of Open Access Journals (Sweden)

    Jamie L Hanson

    2011-05-01

    Full Text Available Facets of the post-natal environment including the type and complexity of environmental stimuli, the quality of parenting behaviors, and the amount and type of stress experienced by a child affects brain and behavioral functioning. Poverty is a type of pervasive experience that is likely to influence biobehavioral processes because children developing in such environments often encounter high levels of stress and reduced environmental stimulation. This study explores the association between socioeconomic status and the hippocampus, a brain region involved in learning and memory that is known to be affected by stress. We employ a voxel-based morphometry analytic framework with region of interest drawing for structural brain images acquired from participants across the socioeconomic spectrum (n = 317. Children from lower income backgrounds had lower hippocampal gray matter density, a measure of volume. This finding is discussed in terms of disparities in education and health that are observed across the socioeconomic spectrum.

  3. Differences between seizure-prone and non-seizure-prone mice with regard to glutamate and GABA receptor binding in the hippocampus and other regions of the brain

    DEFF Research Database (Denmark)

    Frandsen, A; Belhage, B; Schousboe, A

    1987-01-01

    Quisqualate-preferring glutamate receptors were determined in membranes from frontal cortex, occipital cortex, hippocampus and cerebellum, from seizure-prone DBA/2J BOM and seizure-resistant C57/BL mice. The animals were studied 21, 27 and 40 days postnatally, i.e., before, during and after the age...... at which DBA mice are most susceptible to seizures. Radio-binding assays were performed using [3H]AMPA in the presence of 100 nM glutamate. Except for the occipital cortex, where no significant differences between the two strains were observed, all areas of the brain of DBA mice exhibited significantly (P...... less than 0.001, t test) higher AMPA binding than the corresponding areas of C57/BL mice at 27 days of age. At pre- and post-susceptible ages, the two strains showed no significant differences in the hippocampus and occipital cortex. A significant difference was observed, however, in the frontal cortex...

  4. [Functional results of cryosurgical procedures in rhegmatogenous retinal detachment including macula region - our experience].

    Science.gov (United States)

    Chrapek, O; Sín, M; Jirková, B; Jarkovský, J; Rehák, J

    2013-10-01

    Aim of this study is to evaluate retrospectively functional results of cryosurgical treatment of uncomplicated, idiopathic rhegmatogenous retinal detachment including macula region in phakic patients operated on at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc, Czech Republic, E.U., during the period 2002 -2013, and to evaluate the significance of the macula detachment duration for the final visual acuity. In the study group were included 56 eyes of 56 patients operated in the years 2003 - 2012 at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc. All patients were phakic and in all of them, the retinal detachment including the macula region was diagnosed. The mean follow-up period of the patients was 8,75 months. The initial and final visual acuity testing were performed. Comparing the initial and final visual acuity we rated the level of the visual acuity change. The result was stated as improved, if the visual acuity improved by 1 or more lines on the ETDRS chart. The result was rated as stabilized, if the visual acuity remained the same or it changed by 1 line of the ETDRS chart only. The result was evaluated as worsened, if the visual acuity decreased by 1 or more lines of the ETDRS chart. In the followed-up group, the authors compared visual acuity levels in patients with the macula detachment duration 10 days and 11 days. For the statistical evaluation of achieved results, the Mann - Whitney U test was used. The visual acuity improved in 49 (87 %), did not changed in 5 (9 %) and worsened in 2 (4 %) patients. The patients with macula detachment duration 10 days achieved statistically significant better visual acuity than patients with macula detachment duration 11 days. Patients with macula detachment duration 10 days have better prognosis for functional result than patients with macula detachment duration 11 days.

  5. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    Science.gov (United States)

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

  6. 77 FR 62535 - Hydro Aluminum North America, Inc., Midwest Region, Including On-Site Leased Workers From...

    Science.gov (United States)

    2012-10-15

    ... Aluminum North America, Inc., Midwest Region, Including On- Site Leased Workers From Employment Group, Aerotek, and Manpower, Kalamazoo, Michigan; Hydro Aluminum North America, Inc., Midwest Region, Including... Aluminum North America, Inc., Kalamazoo, Michigan. The subject worker group includes on-site leased workers...

  7. Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

    Science.gov (United States)

    Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2016-01-01

    Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.

  8. Automatic treatment of multiple wound coils in 3D finite element problems including multiply connected regions

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, P.J.; Lai, H.C.; Eastham, J.F.; Al-Akayshee, Q.H. [Univ. of Bath (United Kingdom)

    1996-05-01

    This paper describes an efficient scheme for incorporating multiple wire wound coils into 3D finite element models. The scheme is based on the magnetic scalar representation with an additional basis for each coil. There are no restrictions on the topology of coils with respect to ferromagnetic and conductor regions. Reduced scalar regions and cuts are automatically generated.

  9. When is the hippocampus involved in recognition memory?

    OpenAIRE

    Barker, Gareth R. I.; Warburton, Elizabeth C.

    2011-01-01

    The role of the hippocampus in recognition memory is controversial. Recognition memory judgments may be made using different types of information, including object familiarity, an object's spatial location, or when an object was encountered. Experiment 1 examined the role of the hippocampus in recognition memory tasks that required the animals to use these different types of mnemonic information. Rats with bilateral cytotoxic lesions in the hippocampus or perirhinal or prefrontal cortex were ...

  10. Neurological complications after 434 MHz microwave hyperthermia of the rat lumbar region including the spinal cord

    NARCIS (Netherlands)

    Franken, N. A.; de Vrind, H. H.; Sminia, P.; Haveman, J.; Troost, D.; Gonzalez Gonzalez, D.

    1992-01-01

    Hyperthermia was applied in the region of the vertebral column from the second to the fifth lumbar vertebra using a ring-shaped 434 MHz microwave radiator. In all experiments temperatures were measured at a 'reference' thermocouple which was placed against the fourth lumbar vertebra. After 60 min of

  11. Is variation management included in regional healthcare governance systems? Some proposals from Italy.

    Science.gov (United States)

    Nuti, Sabina; Seghieri, Chiara

    2014-01-01

    The Italian National Health System, which follows a Beveridge model, provides universal healthcare coverage through general taxation. Universal coverage provides uniform healthcare access to citizens and is the characteristic usually considered the added value of a welfare system financed by tax revenues. Nonetheless, wide differences in practice patterns, health outcomes and regional usages of resources that cannot be justified by differences in patient needs have been demonstrated to exist. Beginning with the experience of the health care system of the Tuscany region (Italy), this study describes the first steps of a long-term approach to proactively address the issue of geographic variation in healthcare. In particular, the study highlights how the unwarranted variation management has been addressed in a region with a high degree of managerial control over the delivery of health care and a consolidated performance evaluation system, by first, considering it a high priority objective and then by actively integrating it into the regional planning and control mechanism. The implications of this study can be useful to policy makers, professionals and managers, and will contribute to the understanding of how the management of variation can be implemented with performance measurements and financial incentives. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. The study of the volume and 1H MRS of the hippocampus in posttraumatic stress disorder

    International Nuclear Information System (INIS)

    Yang Bo; Zhou Yicheng; Xia Jun; Xia Liming; Wang Chengyuan

    2006-01-01

    Objective: To study the changes of the hippocampus metabolites and the hippoeampus volume with MRI, and to explore the posibble pathophysiology of the hippocampus injure in posttraumatic stress disorder(PTSD). Methods: Seventeen cases of PTSD and 17 age-matched normal subjects (control subjects) were examined on a clinical 1.5 T MRI/MRS system. Proton multi-voxel spectroscopy imaging ( 1 H-MRSI) was obtained from two sides of the hippocampus region. The metabolites included N-acetylaspartate (NAA), creatine and phosphocreatine (Cr), and choline-containing compounds (Cho). The values of NAA, Cr, and Cho were calculated by integration of their peaks. The volume of the hippocampus of the two sides and the brain volume were measured with volume analysis software, and the resulting data were normalized according to the individual brain volume. Both the value of the metabolites and volume of the hippocampus were compared between the two groups respectively. Results: The volumes of left and right hippocampus were (2130±221 )mm 3 and (2571±190) mm 3 in PTSD cases, and they were (2382±157) mm 3 and (2572±186) mm 3 in the control subjects. The volume of left hippocampus of PTSD was smaller than that of the control subjects (P 0.05). NAA and Cr was significantly reduced in PTSD (Left: NAA= 2.8±0.7, Cr=2.3±0.6; Right: NAA 2.9±0.9, Cr=2.3±0.7) bilaterally when compared with those of control subjects (Left: NAA=3.8±0.8, Cr=2.7±0.5; Right: NAA=3.9±0.8, Cr=2.8±0.5) (P 0.05). Conclusion: The results of this study add support to the view that the hippocampus may participate in the pathophysiology of PTSD, and the findings of volume and metabolite changes in the hippocampus has great value in diagnosing PTSD and in exploring the posibble pathophysiology mechanisms of hippocampus injure in PTSD. (authors)

  13. 75 FR 6355 - Manufacturing Extension Partnership (MEP) Availability of Funds for Three Regions Including the...

    Science.gov (United States)

    2010-02-09

    ... working with manufacturers. The proposal should include plans for integration into the MEP national system... Center? i. Organizational Structure. Completeness and appropriateness of the organizational structure...

  14. Stress, memory, and the hippocampus.

    Science.gov (United States)

    Wingenfeld, Katja; Wolf, Oliver T

    2014-01-01

    Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders. © 2014 S. Karger AG, Basel

  15. Land Use in LCA: Including Regionally Altered Precipitation to Quantify Ecosystem Damage.

    Science.gov (United States)

    Lathuillière, Michael J; Bulle, Cécile; Johnson, Mark S

    2016-11-01

    The incorporation of soil moisture regenerated by precipitation, or green water, into life cycle assessment has been of growing interest given the global importance of this resource for terrestrial ecosystems and food production. This paper proposes a new impact assessment model to relate land and water use in seasonally dry, semiarid, and arid regions where precipitation and evapotranspiration are closely coupled. We introduce the Precipitation Reduction Potential midpoint impact representing the change in downwind precipitation as a result of a land transformation and occupation activity. Then, our end-point impact model quantifies terrestrial ecosystem damage as a function of precipitation loss using a relationship between woody plant species richness, water and energy regimes. We then apply the midpoint and end-point models to the production of soybean in Southeastern Amazonia which has resulted from the expansion of cropland into tropical forest, with noted effects on local precipitation. Our proposed cause-effect chain represents a complementary approach to previous contributions which have focused on water consumption impacts and/or have represented evapotranspiration as a loss to the water cycle.

  16. Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: Evidence from resting-state fMRI

    International Nuclear Information System (INIS)

    Zhang, Wei; Liu, Xianjun; Zhang, Yi; Song, Lingheng; Hou, Jingming; Chen, Bing; He, Mei; Cai, Ping; Lii, Haitao

    2014-01-01

    Objective: The hippocampus expresses high levels of thyroid hormone receptors, suggesting that hippocampal functions, including cognition and regulation of mood, can be disrupted by thyroid pathology. Indeed, structural and functional alterations within the hippocampus have been observed in hyperthyroid patients. In addition to internal circuitry, hippocampal processing is dependent on extensive connections with other limbic and neocortical structures, but the effects of hyperthyroidism on functional connectivity (FC) with these areas have not been studied. The purpose of this study was to investigate possible abnormalities in the FC between the hippocampus and other neural structures in hyperthyroid patients using resting-state fMRI. Methods: Seed-based correlation analysis was performed on resting-state fMRI data to reveal possible differences in hippocampal FC between hyperthyroid patients and healthy controls. Correlation analysis was used to investigate the relationships between the strength of FC in regions showing significant group differences and clinical variables. Results: Compared to controls, hyperthyroid patients showed weaker FC between the bilateral hippocampus and both the bilateral anterior cingulate cortex (ACC) and bilateral posterior cingulate cortex (PCC), as well as between the right hippocampus and right medial orbitofrontal cortex (mOFC). Disease duration was negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC and PCC. Levels of depression and anxiety were negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC. Conclusion: Decreased functional connectivity between the hippocampus and bilateral ACC, PCC, and right mOFC may contribute to the emotional and cognitive dysfunction associated with hyperthyroidism

  17. Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: Evidence from resting-state fMRI

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei, E-mail: will.zhang.1111@gmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Sichuan Provincial Corps Hospital, Chinese People' s Armed Police Forces, Leshan 614000 (China); Liu, Xianjun, E-mail: xianjun6.liu@gmail.com [Department of Radiology, Sichuan Provincial Corps Hospital, Chinese People' s Armed Police Forces, Leshan 614000 (China); Zhang, Yi, E-mail: yi.zhang.0833@gmail.com [Department of Radiology, Sichuan Provincial Corps Hospital, Chinese People' s Armed Police Forces, Leshan 614000 (China); Song, Lingheng, E-mail: songlh1023@hotmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Hou, Jingming, E-mail: jingminghou@hotmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Chen, Bing, E-mail: chenbing3@medmail.com.cn [Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); He, Mei, E-mail: sunnusunny0105@gmail.com [Department of Clinical Psychology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cai, Ping, E-mail: pingc_ddd@sina.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Lii, Haitao, E-mail: haitaolii023@gmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2014-10-15

    Objective: The hippocampus expresses high levels of thyroid hormone receptors, suggesting that hippocampal functions, including cognition and regulation of mood, can be disrupted by thyroid pathology. Indeed, structural and functional alterations within the hippocampus have been observed in hyperthyroid patients. In addition to internal circuitry, hippocampal processing is dependent on extensive connections with other limbic and neocortical structures, but the effects of hyperthyroidism on functional connectivity (FC) with these areas have not been studied. The purpose of this study was to investigate possible abnormalities in the FC between the hippocampus and other neural structures in hyperthyroid patients using resting-state fMRI. Methods: Seed-based correlation analysis was performed on resting-state fMRI data to reveal possible differences in hippocampal FC between hyperthyroid patients and healthy controls. Correlation analysis was used to investigate the relationships between the strength of FC in regions showing significant group differences and clinical variables. Results: Compared to controls, hyperthyroid patients showed weaker FC between the bilateral hippocampus and both the bilateral anterior cingulate cortex (ACC) and bilateral posterior cingulate cortex (PCC), as well as between the right hippocampus and right medial orbitofrontal cortex (mOFC). Disease duration was negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC and PCC. Levels of depression and anxiety were negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC. Conclusion: Decreased functional connectivity between the hippocampus and bilateral ACC, PCC, and right mOFC may contribute to the emotional and cognitive dysfunction associated with hyperthyroidism.

  18. Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: evidence from resting-state fMRI.

    Science.gov (United States)

    Zhang, Wei; Liu, Xianjun; Zhang, Yi; Song, Lingheng; Hou, Jingming; Chen, Bing; He, Mei; Cai, Ping; Lii, Haitao

    2014-10-01

    The hippocampus expresses high levels of thyroid hormone receptors, suggesting that hippocampal functions, including cognition and regulation of mood, can be disrupted by thyroid pathology. Indeed, structural and functional alterations within the hippocampus have been observed in hyperthyroid patients. In addition to internal circuitry, hippocampal processing is dependent on extensive connections with other limbic and neocortical structures, but the effects of hyperthyroidism on functional connectivity (FC) with these areas have not been studied. The purpose of this study was to investigate possible abnormalities in the FC between the hippocampus and other neural structures in hyperthyroid patients using resting-state fMRI. Seed-based correlation analysis was performed on resting-state fMRI data to reveal possible differences in hippocampal FC between hyperthyroid patients and healthy controls. Correlation analysis was used to investigate the relationships between the strength of FC in regions showing significant group differences and clinical variables. Compared to controls, hyperthyroid patients showed weaker FC between the bilateral hippocampus and both the bilateral anterior cingulate cortex (ACC) and bilateral posterior cingulate cortex (PCC), as well as between the right hippocampus and right medial orbitofrontal cortex (mOFC). Disease duration was negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC and PCC. Levels of depression and anxiety were negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC. Decreased functional connectivity between the hippocampus and bilateral ACC, PCC, and right mOFC may contribute to the emotional and cognitive dysfunction associated with hyperthyroidism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Evolution of a Greenland Ice sheet Including Shelves and Regional Sea Level Variations

    Science.gov (United States)

    Bradley, Sarah; Reerink, Thomas; van de Wal, Roderik S. W.; Helsen, Michiel; Goelzer, Heiko

    2016-04-01

    Observational evidence, including offshore moraines and marine sediment cores infer that at the Last Glacial maximum (LGM) the Greenland ice sheet (GIS) grounded out across the Davis Strait into Baffin Bay, with fast flowing ice streams extending out to the continental shelf break along the NW margin. These observations lead to a number of questions as to weather the GIS and Laurentide ice sheet (LIS) coalesced during glacial maximums, and if so, did a significant ice shelf develop across Baffin Bay and how would such a configuration impact on the relative contribution of these ice sheets to eustatic sea level (ESL). Most previous paleo ice sheet modelling simulations of the GIS recreated an ice sheet that either did not extend out onto the continental shelf or utilised a simplified marine ice parameterisation to recreate an extended GIS, and therefore did not fully include ice shelf dynamics. In this study we simulate the evolution of the GIS from 220 kyr BP to present day using IMAU-ice; a 3D thermodynamical ice sheet model which fully accounts for grounded and floating ice, calculates grounding line migration and ice shelf dynamics. As there are few observational estimates of the long-term (yrs) sub marine basal melting rates (mbm) for the GIS, we developed a mbm parameterization within IMAU-ice controlled primarily by changes in paleo water depth. We also investigate the influence of the LIS on the GIS evolution by including relative sea level forcing's derived from a Glacial Isostatic Adjustment model. We will present results of how changes in the mbm directly impacts on the ice sheet dynamics, timing and spatial extent of the GIS at the glacial maximums, but also on the rate of retreat and spatial extent at the Last interglacial (LIG) minimum. Results indicate that with the inclusion of ice shelf dynamics, a larger GIS is generated which is grounded out into Davis strait, up to a water depth of -750 m, but significantly reduces the GIS contribution to Last

  20. Region-specific roles of the prelimbic cortex, the dorsal CA1, the ventral DG and ventral CA1 of the hippocampus in the fear return evoked by a sub-conditioning procedure in rats.

    Science.gov (United States)

    Fu, Juan; Xing, Xiaoli; Han, Mengfi; Xu, Na; Piao, Chengji; Zhang, Yue; Zheng, Xigeng

    2016-02-01

    The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of these structures in the fear return evoked by a sub-threshold conditioning (SC) is not known. In the present experiments, we first examined specific roles of the prelimbic cortex (PL), the dorsal hippocampus (DH, the dorsal CA1 area in particular), the ventral hippocampus (the ventral dentate gyrus (vDG) and the ventral CA1 area in particular) in this fear return process. Then we examined the role of connections between PL and vCA1 with this behavioral approach. Rats were subjected to five tone-shock pairings (1.0-mA shock) to induce conditioned fear (freezing), followed by three fear extinction sessions (25 tone-alone trials each session). After a post-test for extinction memory, some rats were retrained with the SC procedure to reinstate tone-evoked freezing. Rat groups were injected with low doses of the GABAA agonist muscimol to selectively inactivate PL, DH, vDG, or vCA1 120 min before the fear return test. A disconnection paradigm with ipsilateral or contralateral muscimol injection of the PL and the vCA1 was used to examine the role of this pathway in the fear return. We found that transient inactivation of these areas significantly impaired fear return (freezing): inactivation of the prelimbic cortex blocked SC-evoked fear return in particular but did not influence fear expression in general; inactivation of the DH area impaired fear return, but had no effect on the extinction retrieval process; both ventral DG and ventral CA1 are required for the return of extinguished fear whereas only ventral DG is required for the extinction retrieval. These findings suggest that PL, DH, vDG, and vCA1 all contribute to the fear

  1. Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Hui Young Lee

    2016-06-01

    Conclusion: Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult.

  2. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien

    2007-01-01

    This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were fou...... of the posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5......This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found...

  3. Report on a collection of Hydroida from the Caribbean region, including an annotated checklist of Caribbean Hydroids

    NARCIS (Netherlands)

    Vervoort, W.

    1968-01-01

    INTRODUCTION The present report deals with a collection of Hydroids from the Zoological Museum, Munich, German Federal Republic (Zoologische Sammlung des Bayerischen Staates, München), collected during various expeditions in the Caribbean region. I have thought it advisable to include in this report

  4. Endogenous synthesis of corticosteroids in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Shimpei Higo

    Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

  5. 1H magnetic resonance spectroscopy metabolite profiles of neonatal rat hippocampus and brainstem regions following early postnatal exposure to intermittent hypoxia

    Science.gov (United States)

    Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor

    2017-03-01

    Most premature infants born at less than 30 weeks gestation are exposed to periods of mild intermittent hypoxia (IH) associated with apnea of prematurity and periodic breathing. In adults, IH associated with sleep apnea causes neurochemical and structural alterations in the brain. However, it is unknown whether IH in the premature infant leads to neurodevelopmental impairment. Quantification of biochemical markers that can precisely identify infants at risk of adverse neurodevelopmental outcome is essential. In vivo 1H magnetic resonance spectroscopy (1H MRS) facilitates the quantification of metabolites from distinct regions of the developing brain. We report the changes in metabolite profiles in the brainstem and hippocampal regions of developing rat brains, resulting from exposure to IH. Rat pups were chosen for study because there is rapid postnatal hippocampal development that occurs during the first 4 weeks in the developing rat brain, which corresponds to the first 2-3 postnatal years of development in humans. The brainstem was examined because of our interest in respiratory control disorders in the newborn and because of brainstem gliosis described in infants who succumb to Sudden Infant Death Syndrome (SIDS). Metabolite profiles were compared between hypoxia treated rat pups (n = 9) and normoxic controls (n = 6). Metabolite profiles were acquired using the Point-RESolved spectroscopy (PRESS) MRS sequence and were quantified using the TARQUIN software. There was a significant difference in the concentrations of creatine (p = 0.031), total creatine (creatine + phosphocreatine) (p = 0.028), and total choline (p = 0.001) in the brainstem, and glycine (p = 0.031) in the hippocampal region. The changes are consistent with altered cellular bioenergetics and metabolism associated with hypoxic insult.

  6. Including capabilities of local actors in regional economic development: Empirical results of local seaweed industries in Sulawesi

    Directory of Open Access Journals (Sweden)

    Mark T.J. Vredegoor

    2013-11-01

    Full Text Available Stimson, et al. (2009 developed one of the most relevant and well known model for Regional Economic Development. This model covers the most important factors related to economic development question. However, this model excludes the social components of development. Local community should be included in terms of the development of a region. This paper introduced to the Stimson model “Skills” and “Knowledge” at the individual level for local actors indicating the capabilities at the individual level and introduced “Human Coordination” for the capabilities at the collective level. In our empirical research we looked at the Indonesian seaweed market with a specific focus on the region of Baubau. This region was chosen because there are hardly any economic developments. Furthermore this study focuses on the poorer community who are trying to improve their situation by the cultivation of Seaweed. Eighteen local informants was interviewed besides additional interviews of informants from educational and governmental institutions in the cities of Jakarta, Bandung and Yogyakarta. The informants selected had a direct or indirect relationship with the region of Baubau. With the support of the empirical data from this region we can confirm that it is worthwhile to include the local community in the model for regional economic development.  The newly added variables: at the individual level; Skills and Knowledge and at the level of the collective: Human Coordination was supported by the empirical material. It is an indication that including the new variables can give regional economic an extra dimension.  In this way we think that it becomes more explicit that “endogenous” means that the people, or variables closely related to them, should be more explicitly included in models trying to capture Regional Economic Development or rephrased as Local Economic Development Keywords:Regional and endogenous development; Fisheries and seaweed

  7. Sleep-dependent directional coupling between human neocortex and hippocampus.

    Science.gov (United States)

    Wagner, Tobias; Axmacher, Nikolai; Lehnertz, Klaus; Elger, Christian E; Fell, Jürgen

    2010-02-01

    Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal-neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex. Copyright 2009 Elsevier Srl. All rights reserved.

  8. The hippocampus and visual perception

    Science.gov (United States)

    Lee, Andy C. H.; Yeung, Lok-Kin; Barense, Morgan D.

    2012-01-01

    In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates. PMID:22529794

  9. The hippocampus and visual perception

    Directory of Open Access Journals (Sweden)

    Andy C. H. Lee

    2012-04-01

    Full Text Available In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe. Instead, these studies point towards a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates.

  10. Recall versus familiarity when recall fails for words and scenes: the differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions.

    Science.gov (United States)

    Ryals, Anthony J; Cleary, Anne M; Seger, Carol A

    2013-01-25

    This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Neurobiological toxicity of radiation in hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Son, Yeong Hoon; Kim, Joong Sun [Research center, Dongnam institute of radiological and Medical Sciences (DIRAMS), Busan (Korea, Republic of); Kim, Sung Ho; Moon, Chang Jong [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of)

    2014-11-15

    Ionizing radiation affects multiple organs, which differ in their apparent response. Nevertheless, the adult brain is less vulnerable to radiation than other radiosensitive organs. Clinically, patients receive partial large-field or whole-brain irradiation for cancer treatment yearly, long-term survivors increases, and thus, radiation induced side effects, including cognitive impairment, will become a major health problem. Although the most commonly reported noxious effects of irradiation occur via damage to DNA and consequent disruption of protein synthesis, there are also specific effects on biochemical pathways that have indirect effects on DNA transcription. The hippocampus dependent memory dysfunction is consistent with the changes in neurogenesis after 1 and 3 dyas after irradiation. At 30 and 90 days following irradiation, mice displayed significant depression-like behaviors. Hippocampal dysfunction during the chronic phase following cranial irradiation may be associated with decreases in the neurogenesis and synaptic plasticity related signals, concomitant with microglial reduction in the hippocampus.

  12. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  13. Circadian Oscillations within the Hippocampus Support Hippocampus-dependent Memory Processing

    Directory of Open Access Journals (Sweden)

    Kristin Lynn Eckel-Mahan

    2012-04-01

    Full Text Available The ability to sustain memories over long periods of time, sometimes even a lifetime, is one of the most remarkable properties of the brain. Much knowledge has been gained over the past few decades regarding the molecular correlates of memory formation. Once a memory is forged, however, the molecular events that provide permanence are as of yet unclear. Studies in multiple organisms have revealed that circadian rhythmicity is important for the formation, stability, and recall of memories [1]. The neuronal events that provide this link need to be explored further. This article will discuss the findings related to the circadian regulation of memory-dependent processes in the hippocampus. Specifically, the circadian-controlled MAP kinase and cAMP signal transduction pathway plays critical roles in the consolidation of hippocampus-dependent memory. A series of studies have revealed the circadian oscillation of this pathway within the hippocampus, an activity that is absent in memory-deficient, transgenic mice lacking Ca2+-stimulated adenylyl cyclases. Interference with these oscillations proceeding the cellular memory consolidation period impairs the persistence of hippocampus-dependent memory. These data suggest that the persistence of long-term memories may depend upon reactivation of this signal transduction pathway in the hippocampus during the circadian cycle. New data reveals the dependence of hippocampal oscillation in MAPK activity on the SCN, again underscoring the importance of this region in maintaining the circadian physiology of memory. Finally, the downstream ramification of these oscillations in terms of gene expression and epigenetics should be considered, as emerging evidence is pointing strongly to a circadian link between epigenetics and long term synaptic plasticity.

  14. Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation.

    Science.gov (United States)

    Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

    2016-01-01

    The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains.

  15. Application of Observed Precipitation in NCEP Global and Regional Data Assimilation Systems, Including Reanalysis and Land Data Assimilation

    Science.gov (United States)

    Mitchell, K. E.

    2006-12-01

    The Environmental Modeling Center (EMC) of the National Centers for Environmental Prediction (NCEP) applies several different analyses of observed precipitation in both the data assimilation and validation components of NCEP's global and regional numerical weather and climate prediction/analysis systems (including in NCEP global and regional reanalysis). This invited talk will survey these data assimilation and validation applications and methodologies, as well as the temporal frequency, spatial domains, spatial resolution, data sources, data density and data quality control in the precipitation analyses that are applied. Some of the precipitation analyses applied by EMC are produced by NCEP's Climate Prediction Center (CPC), while others are produced by the River Forecast Centers (RFCs) of the National Weather Service (NWS), or by automated algorithms of the NWS WSR-88D Radar Product Generator (RPG). Depending on the specific type of application in data assimilation or model forecast validation, the temporal resolution of the precipitation analyses may be hourly, daily, or pentad (5-day) and the domain may be global, continental U.S. (CONUS), or Mexico. The data sources for precipitation include ground-based gauge observations, radar-based estimates, and satellite-based estimates. The precipitation analyses over the CONUS are analyses of either hourly, daily or monthly totals of precipitation, and they are of two distinct types: gauge-only or primarily radar-estimated. The gauge-only CONUS analysis of daily precipitation utilizes an orographic-adjustment technique (based on the well-known PRISM precipitation climatology of Oregon State University) developed by the NWS Office of Hydrologic Development (OHD). The primary NCEP global precipitation analysis is the pentad CPC Merged Analysis of Precipitation (CMAP), which blends both gauge observations and satellite estimates. The presentation will include a brief comparison between the CMAP analysis and other global

  16. The effect of alcoholic extract of Panicum miliaceum L. seed on hippocampus neuronal density in male mouse

    Directory of Open Access Journals (Sweden)

    Arezoo Bornarodi

    2017-08-01

    Full Text Available Background: Hippocampus organization is a part of temporal lobe, which consists of several sections including hippocampal body, dentate gyrus and subiculum. Panicum miliaceum L. contains proteins, vitamins and antioxidants for human health. This study was conducted to examine the effect of the alcoholic extract of the seed of Panicum miliaceum L. plant on hippocampus neuronal density. Materials and Methods: In this experimental study, 24 male mice were divided into 4 groups (n=6, each group. The alcoholic extract of the seed of the Panicum miliaceum L. plant was prepared by soxhlet extraction. Three doses of the extract 25, 50, 75 mg/kg were intraperitoneally injected to 3 treatment groups for 21 days and the control group received normal saline injection. At the end of the experiment, the animals were anesthetized and after perfusion, their brains were removed from the skull. After tissue processing, slices of the brain were prepared and stained. Then, different regions of the hippocampus were photographed and neuronal densities were evaluated. Results: Results showed that the neuronal density in the CA1, CA3 regions of the group treated with 50 mg/kg of the alcoholic extract and in all regions of hippocampus (CA1,CA2,CA3 in groups treated with dose of 75 mg/kg of the alcoholic extract had a significant increase compared to the control group (P<0.05. Conclusion: The present study shows that the alcoholic extract of the seed of Panicum miliaceum L. plant increases neuronal density and induces neurogenesis in the mouse hippocampus.

  17. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    International Nuclear Information System (INIS)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V_1_0_0. All of the other measured dosimetric parameters including the V_9_5, V_9_9, and D_1_0_0 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  18. Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

    Science.gov (United States)

    Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of

  19. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  20. Bird species and numbers of birds in oak savannas of the Southwestern Borderlands region including effects of burning

    Science.gov (United States)

    Peter F. Ffolliott; Hui Chen; Gerald J. Gottfried

    2011-01-01

    Oak savannas of the Southwestern Borderlands region provide food, cover, and sites for nesting, roosting, and perching for a diversity of bird species. The results of a five-year (2003-2007) study of bird species, numbers of birds, and their diversities in the naturally occurring (unburned) oak savannas of the region are reported in this paper. Effects of cool-season...

  1. Brain Circuits of Methamphetamine Place Reinforcement Learning: The Role of the Hippocampus-VTA Loop.

    Science.gov (United States)

    Keleta, Yonas B; Martinez, Joe L

    2012-03-01

    The reinforcing effects of addictive drugs including methamphetamine (METH) involve the midbrain ventral tegmental area (VTA). VTA is primary source of dopamine (DA) to the nucleus accumbens (NAc) and the ventral hippocampus (VHC). These three brain regions are functionally connected through the hippocampal-VTA loop that includes two main neural pathways: the bottom-up pathway and the top-down pathway. In this paper, we take the view that addiction is a learning process. Therefore, we tested the involvement of the hippocampus in reinforcement learning by studying conditioned place preference (CPP) learning by sequentially conditioning each of the three nuclei in either the bottom-up order of conditioning; VTA, then VHC, finally NAc, or the top-down order; VHC, then VTA, finally NAc. Following habituation, the rats underwent experimental modules consisting of two conditioning trials each followed by immediate testing (test 1 and test 2) and two additional tests 24 h (test 3) and/or 1 week following conditioning (test 4). The module was repeated three times for each nucleus. The results showed that METH, but not Ringer's, produced positive CPP following conditioning each brain area in the bottom-up order. In the top-down order, METH, but not Ringer's, produced either an aversive CPP or no learning effect following conditioning each nucleus of interest. In addition, METH place aversion was antagonized by coadministration of the N-methyl-d-aspartate (NMDA) receptor antagonist MK801, suggesting that the aversion learning was an NMDA receptor activation-dependent process. We conclude that the hippocampus is a critical structure in the reward circuit and hence suggest that the development of target-specific therapeutics for the control of addiction emphasizes on the hippocampus-VTA top-down connection.

  2. Including local rainfall dynamics and uncertain boundary conditions into a 2-D regional-local flood modelling cascade

    Science.gov (United States)

    Bermúdez, María; Neal, Jeffrey C.; Bates, Paul D.; Coxon, Gemma; Freer, Jim E.; Cea, Luis; Puertas, Jerónimo

    2016-04-01

    Flood inundation models require appropriate boundary conditions to be specified at the limits of the domain, which commonly consist of upstream flow rate and downstream water level. These data are usually acquired from gauging stations on the river network where measured water levels are converted to discharge via a rating curve. Derived streamflow estimates are therefore subject to uncertainties in this rating curve, including extrapolating beyond the maximum observed ratings magnitude. In addition, the limited number of gauges in reach-scale studies often requires flow to be routed from the nearest upstream gauge to the boundary of the model domain. This introduces additional uncertainty, derived not only from the flow routing method used, but also from the additional lateral rainfall-runoff contributions downstream of the gauging point. Although generally assumed to have a minor impact on discharge in fluvial flood modeling, this local hydrological input may become important in a sparse gauge network or in events with significant local rainfall. In this study, a method to incorporate rating curve uncertainty and the local rainfall-runoff dynamics into the predictions of a reach-scale flood inundation model is proposed. Discharge uncertainty bounds are generated by applying a non-parametric local weighted regression approach to stage-discharge measurements for two gauging stations, while measured rainfall downstream from these locations is cascaded into a hydrological model to quantify additional inflows along the main channel. A regional simplified-physics hydraulic model is then applied to combine these inputs and generate an ensemble of discharge and water elevation time series at the boundaries of a local-scale high complexity hydraulic model. Finally, the effect of these rainfall dynamics and uncertain boundary conditions are evaluated on the local-scale model. Improvements in model performance when incorporating these processes are quantified using observed

  3. The role of the hippocampus in recognition memory.

    Science.gov (United States)

    Bird, Chris M

    2017-08-01

    Many theories of declarative memory propose that it is supported by partially separable processes underpinned by different brain structures. The hippocampus plays a critical role in binding together item and contextual information together and processing the relationships between individual items. By contrast, the processing of individual items and their later recognition can be supported by extrahippocampal regions of the medial temporal lobes (MTL), particularly when recognition is based on feelings of familiarity without the retrieval of any associated information. These theories are domain-general in that "items" might be words, faces, objects, scenes, etc. However, there is mixed evidence that item recognition does not require the hippocampus, or that familiarity-based recognition can be supported by extrahippocampal regions. By contrast, there is compelling evidence that in humans, hippocampal damage does not affect recognition memory for unfamiliar faces, whilst recognition memory for several other stimulus classes is impaired. I propose that regions outside of the hippocampus can support recognition of unfamiliar faces because they are perceived as discrete items and have no prior conceptual associations. Conversely, extrahippocampal processes are inadequate for recognition of items which (a) have been previously experienced, (b) are conceptually meaningful, or (c) are perceived as being comprised of individual elements. This account reconciles findings from primate and human studies of recognition memory. Furthermore, it suggests that while the hippocampus is critical for binding and relational processing, these processes are required for item recognition memory in most situations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

    Science.gov (United States)

    Daskalakis, Nikolaos P.; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M.

    2015-01-01

    Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders. PMID:26635521

  5. Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Nikolaos P Daskalakis

    2015-11-01

    Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  6. A critical role of the human hippocampus in an electrophysiological measure of implicit memory

    Science.gov (United States)

    Addante, Richard James

    2015-01-01

    The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400–600ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400–600 msec, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analysis were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors were systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that is beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures – but function in different physiological ways. PMID:25562828

  7. Historical and contemporary population genetic connectivity of the European short-snouted seahorse Hippocampus hippocampus and implications for management.

    Science.gov (United States)

    Woodall, L C; Koldewey, H J; Shaw, P W

    2011-06-01

    This first genetic study of Hippocampus hippocampus covers the species' entire geographic range and employs two mtDNA markers (control region and cytochrome b) to establish patterns of population structuring. A total of 255 specimens from 21 locations were used to obtain 89 concatenated haplotypes. The common haplotype was present in all but one population, however, most haplotypes were unique. The haplotype network had a star-like construction, suggesting expansion from a bottleneck event. F(ST) and AMOVA revealed population subdivision into three geographic regions (English Channel + Bay of Biscay, Mediterranean Sea + Atlantic Ocean Iberian coast + Macaronesian Islands, and West Africa) with barriers to gene flow indentified at Cape Finisterre and the Cape Verde frontal zone. Neutrality tests and nested clade analysis suggest a complex demographic history, with both historic events and contemporary processes shaping patterns of genetic differentiation. The genetic population subdivision detected in this study indicates that H. hippocampus should be managed as three separate units. This is especially pertinent as H. hippocampus populations within the West African region are the only ones known to be specifically targeted for exploitation. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

  8. Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

    Science.gov (United States)

    Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

    2008-07-16

    Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

  9. Receptor autoradiography in the hippocampus of man and rat

    International Nuclear Information System (INIS)

    Zilles, K.

    1988-01-01

    This chapter deals with the following questions: regional distribution of binding sites for 5-HT, glutamate, and acetylcholine in Ammon's horn and the dentate gyrus of rat and human brain; comparison of receptor distribution and neuronal pathways with identified transmitters; correlation of region-specific densities between different receptors and receptor subtypes (colocalization of different receptors on the level of hippocampal layers) and comparison of receptor distribution in human and rat hippocampus

  10. Tennessee Valley region study: potential year 2000 radiological dose to population resulting from nuclear facility operations. [Includes glossary

    Energy Technology Data Exchange (ETDEWEB)

    None

    1978-06-01

    A companion report, DOE/ET-0064/1, presents a geographic, cultural, and demographic profile of the Tennessee Valley Region study area. This report describes the calculations of radionuclide release and transport and of the resultant dose to the regional population, assuming a projected installed capacity of 220,000 MW in the year 2000, of which 144,000 MW would be nuclear. All elements of the fuel cycle were assumed to be in operation. The radiological dose was calculated as a one-year dose based on ingestion of 35 different food types as well as for nine non-food pathways, and was reported as dose to the total body and for six specific organs for each of four age groups (infant, child, teen, and adult). Results indicate that the average individual would receive an incremental dose of 7 x 10/sup -4/ millirems in the year 2000 from the operation of nuclear facilities within and adjacent to the region, five orders of magnitude smaller than the dose from naturally occurring radiation in the area. The major contributor to dose was found to be tritium, and the most significant pathways were immersion in air, inhalation of air, transpiration of tritium (absorption through the skin), and exposure radionuclide-containing soil. 60 references.

  11. Creating a false memory in the hippocampus.

    Science.gov (United States)

    Ramirez, Steve; Liu, Xu; Lin, Pei-Ann; Suh, Junghyup; Pignatelli, Michele; Redondo, Roger L; Ryan, Tomás J; Tonegawa, Susumu

    2013-07-26

    Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram-bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.

  12. MORPHOLOGICAL CHANGES IN THE HIPPOCAMPUS OF RATS IN ACCELERATED AGING

    Directory of Open Access Journals (Sweden)

    K. Yu. Maksimova

    2014-01-01

    Full Text Available The aim of this work was the analysis of structural changes with age in the hippocampus of senescenceaccelerated OXYS rats when signs of accelerated brain aging are missing (age 14 days, developments (age 5 months, and active progresses (age 15 months. The study was performed on 15 OXYS rats and 15 Wistar rats (as a control. After dislocation, brains were dissected, fixed with 10% formalin, embedded in paraffin, and serially cut in coronal sections (5μm thickness. These sections were stained with Cresyl violet and examined with a photomicroscope (Carl Zeiss Axiostar plus, Germany. The total number of hippocampal pyramidal cells in the CA1, CA3 and the dentate gyrus regions were estimated in 14-dayold, 5and 15-month-old OXYS and Wistar rats (n = 5 on the 5 slices of each brain sections. The number of neurons with chromatolysis, hyperchromatic with darkly stained cytoplasm and shrunken neurons were calculated as degenerative neurons. The pictures obtained with the program Carl Zeiss Axio Vision 8.0 with increasing 10  100, determined the average area bodies and nuclei of neurons (mkm2. The significant structural changes of neurons in the CA1, CA3 and dentate gyrus regions of the hippocampus in OXYS rats at 5 month of age are revealed by light microscopy. This results indicates the early develop neurodegeneration in OXYS rats. The most pronounced morphological changes occur in the CA1 region of the hippocampus of OXYS rats and irreversible. The degenerative changes of neurons in the hippocampus increases by the age of 15 months. Morphometric analysis of the average area of bodies and the nuclei of hippocampal neurons in CA1, CA3 and the dentate gyrus regions of OXYS and Wistar rats at 14 days of age showed no significant interline differences. At 5 months of age in the CA1 region of the hippocampus of OXYS rats was determined a significantly lower average body size and nuclei of pyramidal neurons compared with Wistar rats. With age, these

  13. Memory of music: roles of right hippocampus and left inferior frontal gyrus.

    Science.gov (United States)

    Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

    2008-01-01

    We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

  14. Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

    Science.gov (United States)

    Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

    2014-07-22

    Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  15. Gene Expression ‏‏‏‏Profiles of BAD and Bcl-xL in the CA1 Region of the Hippocampus Following Global Ischemic/Reperfusion and FK-506 Administration.

    Science.gov (United States)

    Badr, Ramak; Hashemi, Mehrdad; Javadi, Gholamreza; Movafagh, Abolfazl; Mahdian, Reza

    2015-12-01

    The hippocampus is a tiny nub in the mammalian brain that is involved in forming, organizing, and storing memories. Global cerebral ischemia (GCI) and reperfusion induced apoptosis lead to cell injury and death. FK-506 is a strong immunosuppressant drug that has neuroprotective effects on the hypoxic-ischemic effects of brain damage. BAD and Bcl-xL are pro-apoptotic and anti-apoptotic genes, respectively. These genes belong to The B-cell lymphoma-2 (Bcl-2) family. In this study, we assessed the neurotrophic properties of FK-506 on expression of the BAD and Bcl-xL genes in the hippocampus following global ischemia and reperfusion. In the present experimental study, adult male Wistar rats were obtained and housed under standard conditions in the Tehran University of Medical Science in Iran. Rats were equally distributed in groups of three among the following groups: normal control, treated-1 (ischemia/reperfusion), and treated-2 (ischemia/reperfusion followed by FK-506). Global ischemia was induced for animals in the treated-1 and treated-2 groups. In treated-2, two doses of FK-506 were injected: one dose as an IV injection immediately after reperfusion and another as an intra-peritoneal (IP) injection after 48 hours. Then, the hippocampus tissue was removed after anaesthetizing the rats. RNA was isolated, cDNA was synthesized, and real-time PCR was performed. Finally, the obtained data were analyzed statistically (P value ˂ 0.05). The quantitative results of real-time PCR show that the mRNA expression ratio of Bcl-xL down-regulated was 0.75 ± 0.06 in the ischemia/reperfusion group versus 1.57 ± 0.09 in the control group (P value BAD up-regulated in the ischemia/reperfusion + FK506 group was 3.65 ± 0.49 compared to Normal control (1.39 ± 0.09) and Ischemia/reperfusion + FK506 was 1.09 ± 0.20 (P value BAD /Bcl-xL) confirmed that expression of the pro-apoptotic gene significantly decreased (P value ˂ 0.001) under the ischemia/reperfusion condition. In contrast

  16. Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

    Directory of Open Access Journals (Sweden)

    Jena B. Hales

    2014-11-01

    Full Text Available The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.

  17. Neural dynamics of the cognitive map in the hippocampus

    OpenAIRE

    Wagatsuma, Hiroaki; Yamaguchi, Yoko

    2007-01-01

    The rodent hippocampus has been thought to represent the spatial environment as a cognitive map. In the classical theory, the cognitive map has been explained as a consequence of the fact that different spatial regions are assigned to different cell populations in the framework of rate coding. Recently, the relation between place cell firing and local field oscillation theta in terms of theta phase precession was experimentally discovered and suggested as a temporal coding mechanism leading t...

  18. Neural dynamics of the cognitive map in the hippocampus.

    Science.gov (United States)

    Wagatsuma, Hiroaki; Yamaguchi, Yoko

    2007-06-01

    The rodent hippocampus has been thought to represent the spatial environment as a cognitive map. In the classical theory, the cognitive map has been explained as a consequence of the fact that different spatial regions are assigned to different cell populations in the framework of rate coding. Recently, the relation between place cell firing and local field oscillation theta in terms of theta phase precession was experimentally discovered and suggested as a temporal coding mechanism leading to memory formation of behavioral sequences accompanied with asymmetric Hebbian plasticity. The cognitive map theory is apparently outside of the sequence memory view. Therefore, theoretical analysis is necessary to consider the biological neural dynamics for the sequence encoding of the memory of behavioral sequences, providing the cognitive map formation. In this article, we summarize the theoretical neural dynamics of the real-time sequence encoding by theta phase precession, called theta phase coding, and review a series of theoretical models with the theta phase coding that we previously reported. With respect to memory encoding functions, instantaneous memory formation of one-time experience was first demonstrated, and then the ability of integration of memories of behavioral sequences into a network of the cognitive map was shown. In terms of memory retrieval functions, theta phase coding enables the hippocampus to represent the spatial location in the current behavioral context even with ambiguous sensory input when multiple sequences were coded. Finally, for utilization, retrieved temporal sequences in the hippocampus can be available for action selection, through the process of reverting theta rhythm-dependent activities to information in the behavioral time scale. This theoretical approach allows us to investigate how the behavioral sequences are encoded, updated, retrieved and used in the hippocampus, as the real-time interaction with the external environment. It may

  19. APOE genotype and age modifies the correlation between cognitive status and metabolites from hippocampus by a 2D 1H-MRS in non-demented elders

    Directory of Open Access Journals (Sweden)

    Zhenyu Yin

    2015-09-01

    Full Text Available Purpose. To examine the associations among age, Apolipoprotein E (APOE genotype, metabolic changes in the hippocampus detected by 2D 1H magnetic resonance spectroscopy (MRS, and neuropsychological measures of cognition in non-demented elders.Materials and Methods. We studied a cohort of 16 cognitively normal controls (CN and 11 amnestic mild cognitive impairment (aMCI patients between 66 and 88 years old who were genotyped for APOE genetic polymorphism. Measurements of 2D1H-MRS metabolites were obtained in the hippocampus region. Adjusting by age among all subjects, the association between metabolic changes and cognitive function was measured by Spearman partial rank-order correlation. The effect of APOE status was measured by separating the subjects into APOE genotype subgroups, including the APOEε4 carriers and APOEε4 non-carriers.Results. In contrast to the CN group matched with age, gender, and education, aMCI patients showed increased myo-inositol (mI/Creatine (Cr ratio only in the right hippocampus. No differences were noted on N-acetylaspartate (NAA/Cr and mI/NAA from bilateral hippocampus, and so was mI/Cr ratio in left hippocampus between aMCI and CN. The mI/Cr ratio from the right hippocampus in non-demented elders was negatively correlated with Montreal Cognitive Assessment (MoCA scores. Whether ε4 genotype or age was added as a covariate, none of the correlation effects remained significant. Additionally, adjusting for age and APOE genotype together, there was no significant correlation between them.Conclusion. Since the higher mI/Cr from the right hippocampus of the patients with aMCI than those from CN, the mI/Cr could be a more specific predictor of general cognitive function in aMCI patients. There is an association between higher mI/Cr in right hippocampus and worse cognitive function for the non-demented older adults, and the correlation could be modified by APOE status and age. That provided a window on objectively

  20. Deletions in 16p13 including GRIN2A in patients with intellectual disability, various dysmorphic features, and seizure disorders of the rolandic region.

    NARCIS (Netherlands)

    Reutlinger, C.; Helbig, I.; Gawelczyk, B.; Subero, J.I.; Tonnies, H.; Muhle, H.; Finsterwalder, K.; Vermeer, S.; Pfundt, R.; Sperner, J.; Stefanova, I.; Gillessen-Kaesbach, G.; Spiczak, S. von; Baalen, A. van; Boor, R.; Siebert, R.; Stephani, U.; Caliebe, A.

    2010-01-01

    Seizure disorders of the rolandic region comprise a spectrum of different epilepsy syndromes ranging from benign rolandic epilepsy to more severe seizure disorders including atypical benign partial epilepsy/pseudo-Lennox syndrome,electrical status epilepticus during sleep, and Landau-Kleffner

  1. Hippocampus sparing in whole-brain radiotherapy. A review

    International Nuclear Information System (INIS)

    Oskan, F.; Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M.

    2014-01-01

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [de

  2. Julius Caesar Arantius (Giulio Cesare Aranzi, 1530-1589) and the hippocampus of the human brain: history behind the discovery.

    Science.gov (United States)

    Bir, Shyamal C; Ambekar, Sudheer; Kukreja, Sunil; Nanda, Anil

    2015-04-01

    Julius Caesar Arantius is one of the pioneer anatomists and surgeons of the 16th century who discovered the different anatomical structures of the human body. One of his prominent discoveries is the hippocampus. At that time, Arantius originated the term hippocampus, from the Greek word for seahorse (hippos ["horse"] and kampos ["sea monster"]). Arantius published his description of the hippocampus in 1587, in the first chapter of his work titled De Humano Foetu Liber. Numerous nomenclatures of this structure, including "white silkworm," "Ammon's horn," and "ram's horn" were proposed by different scholars at that time. However, the term hippocampus has become the most widely used in the literature.

  3. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  4. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  5. Hippocampus in health and disease: An overview

    Directory of Open Access Journals (Sweden)

    Kuljeet Singh Anand

    2012-01-01

    Full Text Available Hippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders. In last decade or so, lot has been learnt about conditions that affect hippocampus and produce changes ranging from molecules to morphology. Progresses in radiological delineation, electrophysiology, and histochemical characterization have made it possible to study this archicerebral structure in greater detail. Present paper attempts to give an overview of hippocampus, both in health and diseases.

  6. Role of the hippocampus on learning and memory functioning and pain modulation

    Institute of Scientific and Technical Information of China (English)

    Haimei Wang

    2008-01-01

    The hippocampus, an important part of the limbic system, is considered to be an important region of the brain for learning and memory functioning. Recent studies have demonstrated that synaptic plasticity is thought to be the basis of learning and memory functioning. A series of studies report that similar synaptic plasticity also exists in the spinal cord in the conduction pathway of pain sensation, which may contribute to hyperalgesia, abnormal pain, and analgesia. The synaptic plasticity of learning and memory functioning and that of the pain conduction pathway have similar mechanisms, which are related to the N-methyl-D-aspartic acid receptor. The hippocampus also has a role in pain modulation. As pain signals can reach the hippocampus, the precise correlation between synaptic plasticity of the pain pathway and that of learning and memory functioning deserves further investigation. The role of the hippocampus in processing pain information requires to be identified.

  7. Fast and robust extraction of hippocampus from MR images for diagnostics of Alzheimer's disease

    DEFF Research Database (Denmark)

    Lötjönen, Jyrki; Wolz, Robin; Koikkalainen, Juha

    2011-01-01

    importance in the clinical decision making. We propose a method for computing automatically the volume of hippocampus using a modified multi-atlas segmentation framework, including an improved initialization of the framework and the correction of partial volume effect. The method produced a high similarity......Assessment of temporal lobe atrophy from magnetic resonance images is a part of clinical guidelines for the diagnosis of prodromal Alzheimer's disease. As hippocampus is known to be among the first areas affected by the disease, fast and robust definition of hippocampus volume would be of great...

  8. Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus.

    Science.gov (United States)

    Chen, Xiao-Rong; Sun, Shi-Cheng; Teng, Shuai-Wen; Li, Liang; Bie, Yi-Fan; Yu, Hui; Li, Da-Li; Chen, Zhe-Yu; Wang, Yue

    2018-03-01

    Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2 +/- and Uhrf2 -/- mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.

  9. A kinetic study of the in vivo incorporation of 65Zn into the rat hippocampus

    International Nuclear Information System (INIS)

    Sato, S.M.; Frazier, J.M.; Goldberg, A.M.

    1984-01-01

    Previous autoradiographical studies utilizing 65 Zn demonstrated an apparent concentration of 65 Zn in the mossy fiber boutons of the hippocampus. To examine the speciation of the 65 Zn pool found in this neuronal pathway, we investigated the in vivo incorporation of systemic 65 Zn into rat hippocampus compared with other brain regions. We were especially interested in kinetically assessing the zinc associated with three previously identified cytosolic zinc-binding species found in the hippocampus. The hypothesis that two of these cytosolic zinc-binding species, a metallothionein-like protein and a putative zinc-glutathione complex, may be responsible for the sequestration of zinc in the hippocampus was tested. It was confirmed that the t 1/2 of hippocampal zinc is longer than other brain regions that were studied. Furthermore, we observed that 65 Zn is incorporated into three cytosolic zinc-binding species in the hippocampus as resolved using Ultrogel AcA 34 gel permeation chromatography. One of these species, the putative zinc-glutathione complex, accumulates zinc more slowly than the other species. The data suggest that the putative zinc-glutathione complex may represent an important 65 Zn pool in the hippocampus. This finding is in accordance with out hypothesis that a zinc-binding species, specifically, the putative zinc-glutathione complex, may be responsible for the sequestration of zinc in the hippocampal mossy boutons

  10. Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval.

    Science.gov (United States)

    Yassa, Michael A; Reagh, Zachariah M

    2013-01-01

    Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being "recontextualization," or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate.

  11. Working memory and the hippocampus.

    Science.gov (United States)

    Baddeley, Alan; Jarrold, Christopher; Vargha-Khadem, Faraneh

    2011-12-01

    A number of studies suggest an important role for the hippocampus in tasks involving visuospatial or relational working memory. We test the generality of this proposal across tasks using a battery designed to investigate the various components of working memory, studying the working memory performance of Jon, who shows a bilateral reduction in hippocampal volume of approximately 50%, comparing him to a group of 48 college students. We measure performance on four complex working memory span measures based on combining visuospatial and verbal storage with visuospatial or verbal concurrent processing as well as measuring Jon's ability to carry out the component storage and processing aspects of these tasks. Jon performed at a consistently high level across our range of tasks. Possible reasons for the apparent disparity between our own findings and earlier studies showing a hippocampal deficit are discussed in terms of both the potential differences in the demands placed on relational memory and of the proposed distinction between egocentric and allocentric visuospatial processing.

  12. Caffeine alters proliferation of neuronal precursors in the adult hippocampus

    OpenAIRE

    Wentz, Christian T.; Magavi, Sanjay S.P.

    2009-01-01

    Neurogenesis continues through adulthood in the hippocampus and olfactory bulb of mammals. Adult neurogenesis has been implicated in learning and memory, and linked with depression. Hippocampal neurogenesis is increased in response to a number of stimuli, including exposure to an enriched environment, increased locomotor activity, and administration of antidepressants. Adult neurogenesis is depressed in response to aging, stress and sleep deprivation. Intriguingly, caffeine modulates a number...

  13. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

    NARCIS (Netherlands)

    Carmichael, O.; Xie, J.; Fletcher, E.; Singh, B.; DeCarli, C.; Olde Rikkert, M.; et al.,

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  14. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

    NARCIS (Netherlands)

    Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; Decarli, Charles; A, Saradha; Abdi, Hervé; Abdul Hadi, Normi; Abdulkadir, Ahmed; Abdullah, Afnizanfaizal; Achuthan, Anusha; Adluru, Nagesh; Aggarwal, Namita; Aghajanian, Jania; Agyemang, Alex; Ahdidan, Jamila; Ahmad, Duaa; Ahmed, Shiek; Ahmed, Fareed; Ahmed, Fayeza; Akbarifar, Roshanak; Akhondi-Asl, Alireza; Aksu, Yaman; Alcauter, Sarael; Daniel, Alexander; Alin, Aylin; Alshuft, Hamza; Alvarez-Linera, Juan; Amin-Mansour, Ali; Anderson, Dallas; Anderson, Jeff; Andorn, Anne; Ang, Amma; Angersbach, Steve; Ansarian, Reza; Appaji, Abhishek; Appannah, Arti; Arfanakis, Konstantinos; Armentrout, Steven; Arrighi, Michael; Arumughababu, S. Vethanayaki; Arunagiri, Vidhya; Ashe-McNalley, Cody; Ashford, Wes; Aurelie, Le Page; Avants, Brian; Aviv, Richard; Avula, Ramesh; Richard, Edo; Schmand, Ben

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  15. Gonorrhoea and gonococcal antimicrobial resistance surveillance networks in the WHO European Region, including the independent countries of the former Soviet Union.

    Science.gov (United States)

    Unemo, Magnus; Ison, Catherine A; Cole, Michelle; Spiteri, Gianfranco; van de Laar, Marita; Khotenashvili, Lali

    2013-12-01

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae has emerged for essentially all antimicrobials following their introduction into clinical practice. During the latest decade, susceptibility to the last remaining options for antimicrobial monotherapy, the extended-spectrum cephalosporins (ESC), has markedly decreased internationally and treatment failures with these ESCs have been verified. In response to this developing situation, WHO and the European Centre for Disease Prevention and Control (ECDC) have published global and region-specific response plans, respectively. One main component of these action/response plans is to enhance the surveillance of AMR and treatment failures. This paper describes the perspectives from the diverse WHO European Region (53 countries), including the independent countries of the former Soviet Union, regarding gonococcal AMR surveillance networks. The WHO European Region has a high prevalence of resistance to all previously recommended antimicrobials, and most of the first strictly verified treatment failures with cefixime and ceftriaxone were also reported from Europe. In the European Union/European Economic Area (EU/EEA), the European gonococcal antimicrobial surveillance programme (Euro-GASP) funded by the ECDC is running. In 2011, the Euro-GASP included 21/31 (68%) EU/EEA countries, and the programme is further strengthened annually. However, in the non-EU/EEA countries, internationally reported and quality assured gonococcal AMR data are lacking in 87% of the countries and, worryingly, appropriate support for establishment of a GASP is still lacking. Accordingly, national and international support, including political and financial commitment, for gonococcal AMR surveillance in the non-EU/EEA countries of the WHO European Region is essential.

  16. A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism.

    Science.gov (United States)

    Wentz, Elisabet; Vujic, Mihailo; Kärrstedt, Ewa-Lotta; Erlandsson, Anna; Gillberg, Christopher

    2014-05-01

    Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.

  17. Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

    Science.gov (United States)

    Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

    2016-01-01

    The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

  18. Implicit transitive inference and the human hippocampus: does intravenous midazolam function as a reversible hippocampal lesion?

    Directory of Open Access Journals (Sweden)

    Greene Anthony J

    2007-09-01

    Full Text Available Abstract Recent advances have led to an understanding that the hippocampus is involved more broadly than explicit or declarative memory alone. Tasks which involve the acquisition of complex associations involve the hippocampus whether the learning is explicit or implicit. One hippocampal-dependent implicit task is transitive inference (TI. Recently it was suggested that implicit transitive inference does not depend upon the hippocampus (Frank, M. J., O'Reilly, R. C., & Curran, T. 2006. When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychological Science, 17, 700–707. The authors demonstrated that intravenous midazolam, which is thought to inactivate the hippocampus, may enhance TI performance. Three critical assumptions are required but not met: 1 that deactivations of other regions could not account for the effect 2 that intravenous midazolam does indeed deactivate the hippocampus and 3 that midazolam influences explicit but not implicit memory. Each of these assumptions is seriously flawed. Consequently, the suggestion that implicit TI does not depend upon the hippocampus is unfounded.

  19. Primary Blast-Induced Changes in Akt and GSK3β Phosphorylation in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Yushan Wang

    2017-08-01

    Full Text Available Traumatic brain injury (TBI due to blast from improvised explosive devices has been a leading cause of morbidity and mortality in recent conflicts in Iraq and Afghanistan. However, the mechanisms of primary blast-induced TBI are not well understood. The Akt signal transduction pathway has been implicated in various brain pathologies including TBI. In the present study, the effects of simulated primary blast waves on the phosphorylation status of Akt and its downstream effector kinase, glycogen synthase kinase 3β (GSK3β, in rat hippocampus, were investigated. Male Sprague-Dawley (SD rats (350–400 g were exposed to a single pulse shock wave (25 psi; ~7 ms duration and sacrificed 1 day, 1 week, or 6 weeks after exposure. Total and phosphorylated Akt, as well as phosphorylation of its downstream effector kinase GSK3β (at serine 9, were detected with western blot analysis and immunohistochemistry. Results showed that Akt phosphorylation at both serine 473 and threonine 308 was increased 1 day after blast on the ipsilateral side of the hippocampus, and this elevation persisted until at least 6 weeks postexposure. Similarly, phosphorylation of GSK3β at serine 9, which inhibits GSK3β activity, was also increased starting at 1 day and persisted until at least 6 weeks after primary blast on the ipsilateral side. In contrast, p-Akt was increased at 1 and 6 weeks on the contralateral side, while p-GSK3β was increased 1 day and 1 week after primary blast exposure. No significant changes in total protein levels of Akt and GSK were observed on either side of the hippocampus at any time points. Immunohistochemical results showed that increased p-Akt was mainly of neuronal origin in the CA1 region of the hippocampus and once phosphorylated, the majority was translocated to the dendritic and plasma membranes. Finally, electrophysiological data showed that evoked synaptic N-methyl-d-aspartate (NMDA receptor activity was

  20. A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

    Science.gov (United States)

    Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

    2012-11-01

    Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. The Role of Hippocampus in the Pathophysiology of Depression

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    Özlem Donat Eker

    2009-06-01

    Full Text Available Hippocampus, as a part of the limbic cortex, has a variety of functions ranging from mating behavior to memory besides its role in the regulation of emotions. The hippocampus has reciprocal interactions of with other brain regions which act in the pathophysiology of major depressive disorder (MDD. Moreover, since the hippocampus is a scene for the neurogenesis, which can be seen as a response to antidepressant treatment, the hippocampus became a focus of attention in neuroimaging studies of MDD. It has been shown that brain derived neurotrophic factor (BDNF, that is responsible from the neurogenesis, is associated with the response to the antidepressants and antidepressant drugs are ineffective if neurogenesis is hindered.Hippocampal atrophy is expected with the decrease of neurogenesis as a result of the lower BDNF levels with the deleterious effects of glucocorticoids in depression. Recurrent and severe depression seems to cause such a volume reduction though first episode MDD subjects do not differ from healthy individuals in respect to their hippocampal volumes (HCVs measured by magnetic resonance imaging methods. One may argue regarding these findings that the atrophy in the hippocampus may be observed in the long term and the decrease in BDNF levels may predispose the volume reduction. Although it has been postulated that smaller HCV as a result of genetic and environmental factors and prior to the illness, may cause a vulnerability to MDD, sufficient evidence has not been accumulated yet and the view that HCV loss develops as depression progresses is widely accepted. Findings that serum BDNF (sBDNF is lower in MDD patients though HCVs of patients do not differ from healthy individuals and the positive correlation of sBDNF with HCV seen only in the patient group support this view. It can be assumed that depressed patients have sensitivity for the fluctuations in BDNF levels. Follow-up studies which consider effects of hipotalamo

  2. Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin.

    Science.gov (United States)

    Roy, M; Lee, R W; Kaarsholm, N C; Thøgersen, H; Brange, J; Dunn, M F

    1990-06-12

    The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence-specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant.

  3. Why avoid the hippocampus? A comprehensive review

    International Nuclear Information System (INIS)

    Gondi, Vinai; Tome, Wolfgang A.; Mehta, Minesh P.

    2010-01-01

    In this review article, we provide a detailed and comprehensive discussion of the rationale for using modern IMRT techniques to spare the subgranular zone of the hippocampus during cranial irradiation. We review the literature on neurocognitive effects of cranial irradiation; discuss clinical and preclinical data associating damage to neural progrenitor cells located in subgranular zone of the hippocampus with radiation-induced neurocognitive decline, specifically in terms of short-term memory formation and recall; and present a review of our pilot investigations into the feasibility and risks of sparing the subgranular zone of the hippocampus during whole-brain radiotherapy for brain metastases. We also introduce our phase II cooperative group clinical trial (RTOG 0933) designed to prospectively evaluate the postulated neurocognitive benefit of hippocampal subgranular zone sparing and scheduled to open in 2010.

  4. Slowly progressive fluent aphasia; Clinical features and an imaging study including MRI, SPECT and PET

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yasuhisa; Momose, Toshimitsu; Watanabe, Toshiaki; Ishikawa, Takashi; Iwata, Makoto (Tokyo Univ. (Japan). Faculty of Medicine); Bando, Mitsuaki

    1991-05-01

    Three patients with slowly progressive fluent aphasia are reported. One of the patients presented with memory disturbance. They were characterized clinically by having selective deficits in vocabulary, which resulted in impairment of confrontation naming, and auditory comprehension. MRI showed an atrophy not only in the left temporal lobe (including the superior, middle and inferior temporal gyri), hippocampus, parahippocampual gyrus, and fusiform gyrus, but also in the left parietal lobe. I-123 IMP SPECT and F-18 FDG PET were used to determine regional cerebral blood flow and regional cerebral metabolic rate, respectively. In addition to the decreased tracer uptake in the left temporal and/or parietal lobe, a decreased uptake was seen in the bilateral basal ganglia, the inner side of the temporal lobe (including the bilateral hippocampus), the right anterior temporal lobe, and the left thalamus. These findings may deny the previous thought that lesions are localized in slowly progressive fluent aphasia. Furthermore, noticeable difficulty in naming, i.e., patients unable to recognize the right answer, are considered attributable to widespread lesions from the whole left temporal lobe, including the hippocampus, to the right temporal lobe. (N.K.).

  5. Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus

    DEFF Research Database (Denmark)

    Motti, Dario; Le Duigou, Caroline; Eugène, Emmanuel

    2010-01-01

    and contralateral hippocampus participated in the status epilepticus. However, neuronal death induced by KA treatment was restricted to the injected hippocampus, although there was some contralateral axonal degeneration. We profiled gene expression changes in dorsal and ventral regions of both the injected...... and contralateral hippocampus. Changes were detected in the expression of 1526 transcripts in samples from three time-points: (i) during the KA-induced status epilepticus, (ii) at 2 weeks, before recurrent seizures emerged, and (iii) at 6 months after seizures emerged. Grouping genes with similar spatio...

  6. Involvement Of BDNF In Age-Dependent Alterations In The Hippocampus

    Directory of Open Access Journals (Sweden)

    Oliver Von Bohlen Und Halbach

    2010-08-01

    Full Text Available It is known since a long time that the hippocampus is sensitive to aging. Thus, there is a reduction in the hippocampal volume during aging. This age-related volume reduction is paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks. This age-related volume reduction of the hippocampus is not a consequence of an age-related loss of hippocampal neurons. The morphological changes associated with aging include reductions in the branching pattern of dendrites, as well as reductions in spine-densities, reductions in the densities of fibers projecting into the hippocampus as well as declines in the rate of neurogenesis. It is very unlikely that a single factor or a single class of molecules is responsible for all these age-related morphological changes in the hippocampus. Nevertheless, it would be of advantage to identify possible neuromodulators or neuropeptides that may contribute to these age-related changes. In this context, growth factors may play an important role in the maintenance of the postnatal hippocampal architecture. In this review it is hypothesized that brain-derived neurotrophic factor (BDNF is a factor critically involved in the regulation of age-related processes in the hippocampus. Moreover, evidences suggest that disturbances in the BDNF-system also affect hippocampal dysfunctions, as e.g. seen in major depression or in Alzheimer disease.

  7. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  8. The hippocampus supports multiple cognitive processes through relational binding and comparison

    Directory of Open Access Journals (Sweden)

    Rosanna Kathleen Olsen

    2012-05-01

    Full Text Available It has been well established that the hippocampus plays a pivotal role in explicit long-term recognition memory. However, findings from amnesia, lesion and recording studies with non-human animals, eye-movement recording studies, and functional neuroimaging have recently converged upon a similar message: the functional reach of the hippocampus extends far beyond explicit recognition memory. Damage to the hippocampus affects performance on a number of cognitive tasks including recognition memory after short and long delays and visual discrimination. Additionally, with the advent of neuroimaging techniques that have fine spatial and temporal resolution, findings have emerged that show the elicitation of hippocampal responses within the first few hundred milliseconds of stimulus/task onset. These responses occur for novel and previously viewed information during a time when perceptual processing is traditionally thought to occur, and long before overt recognition responses are made. We propose that the hippocampus is obligatorily involved in the binding of disparate elements across both space and time, and in the comparison of such relational memory representations. Furthermore, the hippocampus supports relational binding and comparison with or without conscious awareness for the relational representations that are formed, retrieved and/or compared. It is by virtue of these basic binding and comparison functions that the reach of the hippocampus extends beyond long-term recognition memory and underlies task performance in multiple cognitive domains.

  9. Hippocampus sparing in whole-brain radiotherapy. A review

    Energy Technology Data Exchange (ETDEWEB)

    Oskan, F. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany); Saarland University Medical Center, Department of Radiation Oncology, Homburg/Saar (Germany); Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany)

    2014-04-15

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [German] Die Technik der Ganzhirnbestrahlung (''whole-brain radiation therapy'', WBRT) hat sich seit der Entwicklung nicht wesentlich veraendert. Allerdings stellten die Neuentwicklung von Techniken wie die intensitaetsmodulierte Strahlentherapie (IMRT), die volumenmodulierte Arc-Therapie (VMAT) oder die helikale Tomotherapie sowie immer groesseres Wissen ueber das neurale Stammzellkompartiment (NSCs) das herkoemmliche Ganzhirn-Paradigma in Frage. Die hippocampusschonende Ganzhirnbestrahlung ist eine neuartige Technik, welche die kritische Region des Hippocampus schont, ohne die Tumorkontrolle zu gefaehrden. Ueber diese Technik gibt es bisher nur eine begrenzte Datenlage im Sinne von Planungs- und Machbarkeitsstudien. Klinische Daten bzgl. der Behandlungsergebnisse fehlen nach wie vor, aber einige prospektive Studien sind im Gange, um nicht nur die Machbarkeit zu belegen, sondern auch das klinische Outcome im Sinne einer verringerten Neurotoxizitaet nachzuweisen. (orig.)

  10. HIF-1α Activation Attenuates IL-6 and TNF-α Pathways in Hippocampus of Rats Following Transient Global Ischemia

    Directory of Open Access Journals (Sweden)

    Jihong Xing

    2016-07-01

    Full Text Available Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1α in regulating pro-inflammatory cytokines (PICs pathway in the rat hippocampus after cardiac arrest (CA induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR. Those PICs include interleukin-1β (IL-1β, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α. Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1α and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1β, IL-6 and TNF-α were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1α and the time courses for HIF-1α and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1α by systemic administration of ML228, HIF-1α activator, significantly attenuated the amplified IL-6/IL-6R and TNF-α /TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1β and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1β, IL-6 and TNF-α and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1α plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1α improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that

  11. Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

    Science.gov (United States)

    Dombrowski, S M; Deshpande, A; Dingwall, C; Leichliter, A; Leibson, Z; Luciano, M G

    2008-03-18

    Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (Phippocampus that corresponded to increased BVd. It was unclear whether increased VEGFR-2(+) and blood vessel expression was related to focal compression alone or in combination with global ischemia/hypoxia conditions as previously described. These findings suggest that VEGFR-2 may play an adaptive role in angiogenesis after CH

  12. Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid–Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder

    Science.gov (United States)

    Ruzicka, W. Brad; Subburaju, Sivan; Benes, Francine M.

    2017-01-01

    IMPORTANCE Dysfunction related to γ-aminobutyric acid (GABA)–ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. OBJECTIVE To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. DESIGN, SETTING, AND PARTICIPANTS This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont,Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. MAIN OUTCOMES AND MEASURES Methylation levels at 1308 GAD1 regulatory network–associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing

  13. Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

    Science.gov (United States)

    Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

    2015-06-01

    Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of

  14. Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: a susceptibility region for neurological dysfunction including developmental and language delay.

    Science.gov (United States)

    Burnside, Rachel D; Pasion, Romela; Mikhail, Fady M; Carroll, Andrew J; Robin, Nathaniel H; Youngs, Erin L; Gadi, Inder K; Keitges, Elizabeth; Jaswaney, Vikram L; Papenhausen, Peter R; Potluri, Venkateswara R; Risheg, Hiba; Rush, Brooke; Smith, Janice L; Schwartz, Stuart; Tepperberg, James H; Butler, Merlin G

    2011-10-01

    The proximal long arm of chromosome 15 has segmental duplications located at breakpoints BP1-BP5 that mediate the generation of NAHR-related microdeletions and microduplications. The classical Prader-Willi/Angelman syndrome deletion is flanked by either of the proximal BP1 or BP2 breakpoints and the distal BP3 breakpoint. The larger Type I deletions are flanked by BP1 and BP3 in both Prader-Willi and Angelman syndrome subjects. Those with this deletion are reported to have a more severe phenotype than individuals with either Type II deletions (BP2-BP3) or uniparental disomy 15. The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes that are not imprinted. Reports of mutations or disturbed expression of these genes appear to impact behavioral and neurological function in affected individuals. Recently, reports of deletions and duplications flanked by BP1 and BP2 suggest an association with speech and motor delays, behavioral problems, seizures, and autism. We present a large cohort of subjects with copy number alteration of BP1 to BP2 with common phenotypic features. These include autism, developmental delay, motor and language delays, and behavioral problems, which were present in both cytogenetic groups. Parental studies demonstrated phenotypically normal carriers in several instances, and mildly affected carriers in others, complicating phenotypic association and/or causality. Possible explanations for these results include reduced penetrance, altered gene dosage on a particular genetic background, or a susceptibility region as reported for other areas of the genome implicated in autism and behavior disturbances.

  15. Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

    2011-01-01

    Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

  16. Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

    2011-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

  17. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    Directory of Open Access Journals (Sweden)

    Lorena Varela-Nallar

    2015-01-01

    Full Text Available Andrographolide (ANDRO is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β, a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

  18. Does the endangered Knysna seahorse, Hippocampus capensis ...

    African Journals Online (AJOL)

    Abstract. The Knysna seahorse, Hippocampus capensis, is an endangered teleost confined to three South African estuaries. Its abundance within these systems is low and distributions are patchy. Consequently, monitoring population sizes is labour- intensive. The aim of this study was to establish if Knynsa seahorses are ...

  19. Coordinating different representations in the hippocampus

    Czech Academy of Sciences Publication Activity Database

    Kelemen, Eduard; Fenton, A.A.

    2016-01-01

    Roč. 129, Mar 2016 (2016), s. 50-59 ISSN 1074-7427 R&D Projects: GA ČR(CZ) GA14-03627S Institutional support: RVO:67985823 Keywords : dynamic functional grouping * multiple representations * cognitive control * hippocampus * overdispersion Subject RIV: FH - Neurology Impact factor: 3.543, year: 2016

  20. Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Paul David Whissell

    2015-09-01

    Full Text Available Cholecystokinin (CCK- and parvalbumin (PV-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behaviour. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV than they were in corresponding primary areas (V1, S1, M1 and Aud1. The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favour the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labelling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

  1. Traveling Theta Waves in the Human Hippocampus

    Science.gov (United States)

    Zhang, Honghui

    2015-01-01

    The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. SIGNIFICANCE STATEMENT We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior–anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

  2. Navigating the auditory scene: an expert role for the hippocampus.

    Science.gov (United States)

    Teki, Sundeep; Kumar, Sukhbinder; von Kriegstein, Katharina; Stewart, Lauren; Lyness, C Rebecca; Moore, Brian C J; Capleton, Brian; Griffiths, Timothy D

    2012-08-29

    Over a typical career piano tuners spend tens of thousands of hours exploring a specialized acoustic environment. Tuning requires accurate perception and adjustment of beats in two-note chords that serve as a navigational device to move between points in previously learned acoustic scenes. It is a two-stage process that depends on the following: first, selective listening to beats within frequency windows, and, second, the subsequent use of those beats to navigate through a complex soundscape. The neuroanatomical substrates underlying brain specialization for such fundamental organization of sound scenes are unknown. Here, we demonstrate that professional piano tuners are significantly better than controls matched for age and musical ability on a psychophysical task simulating active listening to beats within frequency windows that is based on amplitude modulation rate discrimination. Tuners show a categorical increase in gray matter volume in the right frontal operculum and right superior temporal lobe. Tuners also show a striking enhancement of gray matter volume in the anterior hippocampus, parahippocampal gyrus, and superior temporal gyrus, and an increase in white matter volume in the posterior hippocampus as a function of years of tuning experience. The relationship with gray matter volume is sensitive to years of tuning experience and starting age but not actual age or level of musicality. Our findings support a role for a core set of regions in the hippocampus and superior temporal cortex in skilled exploration of complex sound scenes in which precise sound "templates" are encoded and consolidated into memory over time in an experience-dependent manner.

  3. Neurocomputational account of memory and perception: Thresholded and graded signals in the hippocampus.

    Science.gov (United States)

    Elfman, Kane W; Aly, Mariam; Yonelinas, Andrew P

    2014-12-01

    Recent evidence suggests that the hippocampus, a region critical for long-term memory, also supports certain forms of high-level visual perception. A seemingly paradoxical finding is that, unlike the thresholded hippocampal signals associated with memory, the hippocampus produces graded, strength-based signals in perception. This article tests a neurocomputational model of the hippocampus, based on the complementary learning systems framework, to determine if the same model can account for both memory and perception, and whether it produces the appropriate thresholded and strength-based signals in these two types of tasks. The simulations showed that the hippocampus, and most prominently the CA1 subfield, produced graded signals when required to discriminate between highly similar stimuli in a perception task, but generated thresholded patterns of activity in recognition memory. A threshold was observed in recognition memory because pattern completion occurred for only some trials and completely failed to occur for others; conversely, in perception, pattern completion always occurred because of the high degree of item similarity. These results offer a neurocomputational account of the distinct hippocampal signals associated with perception and memory, and are broadly consistent with proposals that CA1 functions as a comparator of expected versus perceived events. We conclude that the hippocampal computations required for high-level perceptual discrimination are congruous with current neurocomputational models that account for recognition memory, and fit neatly into a broader description of the role of the hippocampus for the processing of complex relational information. © 2014 Wiley Periodicals, Inc.

  4. Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

    Science.gov (United States)

    Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

    2016-01-20

    Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

  5. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    Science.gov (United States)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  6. Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

    Science.gov (United States)

    Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2018-03-01

    Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated

  7. Neurosteroids in Adult Hippocampus of Male and Female Rodents: Biosynthesis and Actions of Sex Steroids

    Directory of Open Access Journals (Sweden)

    Yasushi Hojo

    2018-04-01

    Full Text Available The brain is not only the target of steroid hormones but also is able to locally synthesize steroids de novo. Evidence of the local production of steroids in the brain has been accumulating in various vertebrates, including teleost fish, amphibia, birds, rodents, non-human primates, and humans. In this review, we mainly focus on the local production of sex steroids in the hippocampal neurons of adult rodents (rats and mice, a center for learning and memory. From the data of the hippocampus of adult male rats, hippocampal principal neurons [pyramidal cells in CA1–CA3 and granule cells in dentate gyrus (DG] have a complete system for biosynthesis of sex steroids. Liquid chromatography with tandem-mass-spectrometry (LC-MS/MS enabled us to accurately determine the levels of hippocampal sex steroids including 17β-estradiol (17β-E2, testosterone (T, and dihydrotestosterone (DHT, which are much higher than those in blood. Next, we review the steroid synthesis in the hippocampus of female rats, since previous knowledge had been biased toward the data from males. Recently, we clarified that the levels of hippocampal steroids fluctuate in adult female rats across the estrous cycle. Accurate determination of hippocampal steroids at each stage of the estrous cycle is of importance for providing the account for the fluctuation of female hippocampal functions, including spine density, long-term potentiation (LTP and long-term depression (LTD, and learning and memory. These functional fluctuations in female had been attributed to the level of circulation-derived steroids. LC-MS/MS analysis revealed that the dendritic spine density in CA1 of adult female hippocampus correlates with the levels of hippocampal progesterone and 17β-E2. Finally, we introduce the direct evidence of the role of hippocampus-synthesized steroids in hippocampal function including neurogenesis, LTP, and memory consolidation. Mild exercise (2 week of treadmill running elevated

  8. Differential activation of amygdala, dorsal and ventral hippocampus following an exposure to a reminder ofunderwater trauma

    Directory of Open Access Journals (Sweden)

    Gilad eRitov

    2014-01-01

    Full Text Available Recollection of emotional memories is attributed in part to the activation of the amygdala and the hippocampus. Recent hypothesis suggest a pivotal role for the ventral hippocampus in traumatic stress processing and emotional memory retrieval. Persistent re-experiencing and intrusive recollections are core symptoms in acute and posttraumatic stress disorders (ASD; PTSD. Such intrusive recollections are often triggered by reminders associated with the trauma.We examined the impact of exposure to a trauma reminder (under water trauma on the activation of the basolateral amygdala (BLA, dorsal and ventral hippocampus. Rats were exposed to underwater trauma and 24 hours later were re-exposed to the context of the trauma. Phosphorylation of the extracellular signal-regulated kinase (ERK was used as a marker for level of activation of these regions. Significant increase in ERK activation was found in the ventral hippocampus and BLA. Such pattern of activation was not found in animals exposed only to the trauma or in animals exposed only to the trauma reminder. Additionally, the dissociative pattern of activation of the ventral hippocampus sub-regions positively correlated with the activation of the BLA.Our findings suggest a specific pattern of neural activation during recollection of a trauma reminder, with a unique contribution of the ventral hippocampus. Measured 24 hrs after the exposure to the traumatic experience, the current findings relate to relatively early stages of traumatic memory consolidation. Understanding the neural mechanisms underlying these initial stages may contribute to developing intervention strategies that could reduce the risk of eventually developing PTSD.

  9. Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus

    Science.gov (United States)

    Whissell, Paul D.; Eng, Dave; Lecker, Irene; Martin, Loren J.; Wang, Dian-Shi; Orser, Beverley A.

    2013-01-01

    Extrasynaptic γ-aminobutyric acid type A (GABAA) receptors that contain the δ subunit (δGABAA receptors) are expressed in several brain regions including the dentate gyrus (DG) and CA1 subfields of the hippocampus. Drugs that increase δGABAA receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABAA receptor–preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABAA receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p.) on memory performance in wild-type (WT) and δGABAA receptor null mutant (Gabrd−/−) mice. Additionally, the effects of THIP on long-term potentiation (LTP), a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd−/− mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd−/− mice, an effect that was blocked by GABAA receptor antagonist bicuculline. Thus, acutely increasing δGABAA receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABAA receptor activity. PMID:24062648

  10. Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus

    Directory of Open Access Journals (Sweden)

    Paul David Whissell

    2013-09-01

    Full Text Available Extrasynaptic γ-aminobutyric acid type A (GABAA receptors that contain the δ subunit (δGABAA receptors are expressed in several brain regions including the dentate gyrus (DG and CA1 subfields of the hippocampus. Drugs that increase δGABAA receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABAA receptor–preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABAA receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p. on memory performance in wild-type (WT and δGABAA receptor null mutant (Gabrd–/– mice. Additionally, the effects of THIP on long-term potentiation (LTP, a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd–/– mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd–/– mice, an effect that was blocked by GABAA receptor antagonist bicuculline. Thus, acutely increasing δGABAA receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABAA receptor activity.

  11. Chronic Intermittent Hypoxia Induces Chronic Low-Grade Neuroinflammation in the Dorsal Hippocampus of Mice.

    Science.gov (United States)

    Sapin, Emilie; Peyron, Christelle; Roche, Frédéric; Gay, Nadine; Carcenac, Carole; Savasta, Marc; Levy, Patrick; Dematteis, Maurice

    2015-10-01

    Obstructive sleep apnea (OSA) induces cognitive impairment that involves intermittent hypoxia (IH). Because OSA is recognized as a low-grade systemic inflammatory disease and only some patients develop cognitive deficits, we investigated whether IH-related brain consequences shared similar pathophysiology and required additional factors such as systemic inflammation to develop. Nine-week-old male C57BL/6J mice were exposed to 1 day, 6 or 24 w of IH (alternating 21-5% FiO2 every 30 sec, 8 h/day) or normoxia. Microglial changes were assessed in the functionally distinct dorsal (dH) and ventral (vH) regions of the hippocampus using Iba1 immunolabeling. Then the study concerned dH, as vH only tended to be lately affected. Seven proinflammatory and anti-inflammatory cytokine messenger RNA (mRNA) were assessed at all time points using semiquantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Similar mRNA analysis was performed after 6 w IH or normoxia associated for the past 3 w with repeated intraperitoneal low-dose lipopolysaccharide or saline. Chronic (6, 24 w) but not acute IH induced significant microglial changes in dH only, including increased density and morphological features of microglia priming. In dH, acute but not chronic IH increased IL-1β and RANTES/CCL5 mRNA, whereas the other cytokines remained unchanged. In contrast, chronic IH plus lipopolysaccharide increased interleukin (IL)-6 and IL10 mRNA whereas lipopolysaccharide alone did not affect these cytokines. The obstructive sleep apnea component intermittent hypoxia (IH) causes low-grade neuroinflammation in the dorsal hippocampus of mice, including early but transient cytokine elevations, delayed but long-term microglial changes, and cytokine response alterations to lipopolysaccharide inflammatory challenge. These changes may contribute to IH-induced cognitive impairment and pathological brain aging. © 2015 Associated Professional Sleep Societies, LLC.

  12. The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

    Science.gov (United States)

    Hermawati, Ery; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2015-09-01

    Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

  13. Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

    Science.gov (United States)

    Sutherland, R J; Lehmann, H

    2011-06-01

    We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Monitoring Regional Forest Disturbances across the US with Near Real Time MODIS NDVI Products included in the ForWarn Forest Threat Early Warning System

    Science.gov (United States)

    Spruce, Joseph; Hargrove, William W.; Gasser, Gerald; Norman, Steve

    2013-01-01

    U.S. forests occupy approx.1/3 of total land area (approx. 304 million ha). Since 2000, a growing number of regionally evident forest disturbances have occurred due to abiotic and biotic agents. Regional forest disturbances can threaten human life and property, bio-diversity and water supplies. Timely regional forest disturbance monitoring products are needed to aid forest health management work. Near Real Time (NRT) twice daily MODIS NDVI data provide a means to monitor U.S. regional forest disturbances every 8 days. Since 2010, these NRT forest change products have been produced and posted on the US Forest Service ForWarn Early Warning System for Forest Threats.

  15. {sup 13}C-METHYL FORMATE: OBSERVATIONS OF A SAMPLE OF HIGH-MASS STAR-FORMING REGIONS INCLUDING ORION-KL AND SPECTROSCOPIC CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Favre, Cécile; Bergin, Edwin A.; Crockett, Nathan R.; Neill, Justin L. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Carvajal, Miguel [Dpto. Física Aplicada, Unidad Asociada CSIC, Facultad de Ciencias Experimentales, Universidad de Huelva, E-21071 Huelva (Spain); Field, David [Department of Physics and Astronomy, University of Aarhus, Ny Munkegade 120, DK-8000 Aarhus C (Denmark); Jørgensen, Jes K.; Bisschop, Suzanne E. [Centre for Star and Planet Formation, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen Ø (Denmark); Brouillet, Nathalie; Despois, Didier; Baudry, Alain [Univ. Bordeaux, LAB, UMR 5804, F-33270, Floirac (France); Kleiner, Isabelle [Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA), CNRS, UMR 7583, Université de Paris-Est et Paris Diderot, 61, Av. du Général de Gaulle, F-94010 Créteil Cedex (France); Margulès, Laurent; Huet, Thérèse R.; Demaison, Jean, E-mail: cfavre@umich.edu, E-mail: miguel.carvajal@dfa.uhu.es [Laboratoire de Physique des Lasers, Atomes et Molécules, UMR CNRS 8523, Université Lille I, F-59655 Villeneuve d' Ascq Cedex (France)

    2015-01-01

    We have surveyed a sample of massive star-forming regions located over a range of distances from the Galactic center for methyl formate, HCOOCH{sub 3}, and its isotopologues H{sup 13}COOCH{sub 3} and HCOO{sup 13}CH{sub 3}. The observations were carried out with the APEX telescope in the frequency range 283.4-287.4 GHz. Based on the APEX observations, we report tentative detections of the {sup 13}C-methyl formate isotopologue HCOO{sup 13}CH{sub 3} toward the following four massive star-forming regions: Sgr B2(N-LMH), NGC 6334 IRS 1, W51 e2, and G19.61-0.23. In addition, we have used the 1 mm ALMA science verification observations of Orion-KL and confirm the detection of the {sup 13}C-methyl formate species in Orion-KL and image its spatial distribution. Our analysis shows that the {sup 12}C/{sup 13}C isotope ratio in methyl formate toward the Orion-KL Compact Ridge and Hot Core-SW components (68.4 ± 10.1 and 71.4 ± 7.8, respectively) are, for both the {sup 13}C-methyl formate isotopologues, commensurate with the average {sup 12}C/{sup 13}C ratio of CO derived toward Orion-KL. Likewise, regarding the other sources, our results are consistent with the {sup 12}C/{sup 13}C in CO. We also report the spectroscopic characterization, which includes a complete partition function, of the complex H{sup 13}COOCH{sub 3} and HCOO{sup 13}CH{sub 3} species. New spectroscopic data for both isotopomers H{sup 13}COOCH{sub 3} and HCOO{sup 13}CH{sub 3}, presented in this study, have made it possible to measure this fundamentally important isotope ratio in a large organic molecule for the first time.

  16. Impact of video games on plasticity of the hippocampus.

    Science.gov (United States)

    West, G L; Konishi, K; Diarra, M; Benady-Chorney, J; Drisdelle, B L; Dahmani, L; Sodums, D J; Lepore, F; Jolicoeur, P; Bohbot, V D

    2017-08-08

    The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in participants using non-spatial memory strategies. Conversely, participants who use hippocampus-dependent spatial strategies showed increased grey matter in the hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the hippocampus or the functionally connected entorhinal cortex. A third study replicated the effect of action video game training on grey matter in the hippocampus. These results show that video games can be beneficial or detrimental to the hippocampal system depending on the navigation strategy that a person employs and the genre of the game.Molecular Psychiatry advance online publication, 8 August 2017; doi:10.1038/mp.2017.155.

  17. [Effects of therapeutic complexes including balneoradonokinesitherapy, electromyostimulation and low-frequency magnetotherapy on regional blood flow in patients with postrraumatic gonarthritis].

    Science.gov (United States)

    Raspopova, E A; Udartsev, E Iu

    2006-01-01

    Balneoradonokinesitherapy alone and its combination with electrostimulation and low-frequency magnetotherapy were used for the treatment of regional blood flow disorders in 76 patients with posttraumatic gonarthritis. Balneoradonokinesitherapy in combination with electromyostimulation improved blood circulation. When low-frequency magnetotherapy was added to the latter complex, the regress of regional blood flow disorders of a damaged extremity was most significant.

  18. Evidence for regional hippocampal damage in patients with schizophrenia

    International Nuclear Information System (INIS)

    Singh, Sadhana; Khushu, Subash; Kumar, Pawan; Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N.

    2018-01-01

    Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ( 1 H MRS) procedures. 1 H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients. (orig.)

  19. Evidence for regional hippocampal damage in patients with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Sadhana; Khushu, Subash; Kumar, Pawan [DRDO, NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi (India); Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N. [RML Hospital, Post Graduate Institute of Medical Education and Research (PGIMER), New Delhi (India)

    2018-02-15

    Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ({sup 1}H MRS) procedures. {sup 1}H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients. (orig.)

  20. Conscious experience and episodic memory: hippocampus at the crossroads.

    Science.gov (United States)

    Behrendt, Ralf-Peter

    2013-01-01

    If an instance of conscious experience of the seemingly objective world around us could be regarded as a newly formed event memory, much as an instance of mental imagery has the content of a retrieved event memory, and if, therefore, the stream of conscious experience could be seen as evidence for ongoing formation of event memories that are linked into episodic memory sequences, then unitary conscious experience could be defined as a symbolic representation of the pattern of hippocampal neuronal firing that encodes an event memory - a theoretical stance that may shed light into the mind-body and binding problems in consciousness research. Exceedingly detailed symbols that describe patterns of activity rapidly self-organizing, at each cycle of the θ rhythm, in the hippocampus are instances of unitary conscious experience that jointly constitute the stream of consciousness. Integrating object information (derived from the ventral visual stream and orbitofrontal cortex) with contextual emotional information (from the anterior insula) and spatial environmental information (from the dorsal visual stream), the hippocampus rapidly forms event codes that have the informational content of objects embedded in an emotional and spatiotemporally extending context. Event codes, formed in the CA3-dentate network for the purpose of their memorization, are not only contextualized but also allocentric representations, similarly to conscious experiences of events and objects situated in a seemingly objective and observer-independent framework of phenomenal space and time. Conscious perception, creating the spatially and temporally extending world that we perceive around us, is likely to be evolutionarily related to more fleeting and seemingly internal forms of conscious experience, such as autobiographical memory recall, mental imagery, including goal anticipation, and to other forms of externalized conscious experience, namely dreaming and hallucinations; and evidence pointing to

  1. Conscious Experience and Episodic Memory: Hippocampus at the Crossroads

    Directory of Open Access Journals (Sweden)

    Ralf-Peter eBehrendt

    2013-05-01

    Full Text Available If an instance of conscious experience of the seemingly objective world around us could be regarded as a newly formed event memory, much as an instance of mental imagery has the content of a retrieved event memory, and if, therefore, the stream of conscious experience could be seen as evidence for ongoing formation of event memories that are linked into episodic memory sequences, then unitary conscious experience could be defined as a symbolic representation of the pattern of hippocampal neuronal firing that encodes an event memory – a theoretical stance that may shed light into the mind-body and binding problems in consciousness research. Exceedingly detailed symbols that describe patterns of activity rapidly self-organizing, at each cycle of the θ rhythm, in the hippocampus are instances of unitary conscious experience that jointly constitute the stream of consciousness. Integrating object information (derived from the ventral visual stream and orbitofrontal cortex with contextual emotional information (from the anterior insula and spatial environmental information (from the dorsal visual stream, the hippocampus rapidly forms event codes that have the informational content of objects embedded in an emotional and spatiotemporally extending context. Event codes, formed in the CA3-dentate network for the purpose of their memorization, are not only contextualized but also allocentric representations, similarly to conscious experiences of events and objects situated in a seemingly objective and observer-independent framework of phenomenal space and time. Conscious perception is likely to be related to more fleeting and seemingly internal forms of conscious experience, such as autobiographical memory recall, mental imagery, including goal anticipation, and to other forms of externalized conscious experience, namely dreaming and hallucinations; and evidence pointing to an important contribution of the hippocampus to these conscious phenomena will

  2. Trapping of dilute ion components in wells and double wells in higher equatorial magnetic regions: A kinetic theory including collisions, varying background and additional fields

    Energy Technology Data Exchange (ETDEWEB)

    Oeien, Alf H.

    2001-08-01

    The component of the ambipolar field along the magnetic field B, though weak, may, acting together with the gravitational field, give rise to along-B ''ambipolar wells'' where light ions (test particles) in the ionosphere in equatorial regions are trapped. We also take into account magnetic field wells, especially in cases when the along-B velocity of test particles are much less than the transverse-B velocities. For heavy ions, or, for light ions high up, when the ambipolar trap ceases to function, the along-B ambipolar- and gravitational field effects may combine with the magnetic field trap to form a double well for the along-B movement of test particles. The magnetic field trap and its contribution to the double well may be nearly stationary for particles obeying the same velocity condition as above even when collisional effects between the test particles and the background plasma are incorporated. Ions trapped in wells like this, may ''feel'' a varying background, for instance because of Earth rotation, that may be incorporated as time-variation of parameters in the along-B motion. An along-B kinetic equation for groups of test particles is solved both for the case of simple wells and for double wells, including time-varying collisional coefficients and additional fields, and in some cases analytic solutions are obtained. Peculiar along-B distribution functions may arise due to the time-dependency of coefficients and to various combinations of collision- and field parameter values. In particular ''breathing'' distributions that alternate between wide and narrow forms in phase-space may arise, and also distributions where strange attractors may play some role.

  3. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  4. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S

    2014-01-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment

  5. Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

    Science.gov (United States)

    Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

    2017-03-01

    Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

  6. Development of short-snouted seahorse (Hippocampus hippocampus, L. 1758): osteological and morphological aspects.

    Science.gov (United States)

    Novelli, B; Otero-Ferrer, F; Socorro, J A; Caballero, M J; Segade-Botella, A; Molina Domínguez, L

    2017-06-01

    Information about early development after male release lags behind studies of juveniles and adult seahorses, and newborn seahorses, similar in shape to adults, are considered juveniles or fry. During early life, Hippocampus hippocampus present behavioural (shift in habitat, from planktonic to benthic) and morphological changes; for this reasons, the aims of this study are to define the stage of development of H. hippocampus after they are expelled from the male brood pouch and to establish direct or indirect development through an osteological analysis. The ossification process was studied in 120 individuals, from their release to 30 days after birth. To analyse the osteological development, Alcian Blue-Alizarin Red double staining technique for bone and cartilage was adapted to this species. At birth, H. hippocampus presents a mainly cartilaginous structure that ossifies in approximately 1 month. The bony armour composed of bony rings and plates develops in 10 days. The caudal fin, a structure absent in juveniles and adult seahorses, is present at birth and progressively disappears with age. The absence of adult osteological structure in newborns, like coronet, bony rings and plates, head spines and components allowing tail prehensile abilities, suggests a metamorphosis before the juvenile stage. During the indirect development, the metamorphic stage started inside brood pouch and followed outside and leads up to reconsider the status of H. hippocampus newborns.

  7. Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro

    Directory of Open Access Journals (Sweden)

    Wang XX

    2016-09-01

    Full Text Available Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

  8. Cellular targets of nitric oxide in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Katalin Bartus

    Full Text Available In the hippocampus, as in many other CNS areas, nitric oxide (NO participates in synaptic plasticity, manifested as changes in pre- and/or postsynaptic function. While it is known that these changes are brought about by cGMP following activation of guanylyl cyclase-coupled NO receptors attempts to locate cGMP by immunocytochemistry in hippocampal slices in response to NO have failed to detect the cGMP elevation where expected, i.e. in the pyramidal neurones. Instead, astrocytes, unidentified varicose fibres and GABA-ergic nerve terminals are reported to be the prominent NO targets, raising the possibility that NO acts indirectly via other cells. We have re-investigated the distribution of cGMP generated in response to endogenous and exogenous NO in hippocampal slices using immunohistochemistry and new conditions designed to optimise cGMP accumulation and, hence, its detectability. The conditions included use of tissue from the developing rat hippocampus, a potent inhibitor of phosphodiesterase-2, and an allosteric enhancer of the NO-receptive guanylyl cyclase. Under these conditions, cGMP was formed in response to endogenous NO and was found in a population of pyramidal cell somata in area CA3 and subiculum as well as in structures described previously. The additional presence of exogenous NO resulted in hippocampal cGMP reaching the highest level recorded for brain tissue (1700 pmol/mg protein and in cGMP immunolabelling throughout the pyramidal cell layer. Populations of axons and interneurones were also stained. According with these results, immunohistochemistry for the common NO receptor β1-subunit indicated widespread expression. A similar staining pattern for the α1-subunit with an antibody used previously in the hippocampus and elsewhere, however, proved to be artefactual. The results indicate that the targets of NO in the hippocampus are more varied and extensive than previous evidence had suggested and, in particular, that the

  9. Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

    Science.gov (United States)

    Barbeau, Emmanuel J; Chauvel, Patrick; Moulin, Christopher J A; Regis, Jean; Liégeois-Chauvel, Catherine

    2017-04-01

    The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Differential Age-Related Changes in Structural Covariance Networks of Human Anterior and Posterior Hippocampus

    Directory of Open Access Journals (Sweden)

    Xinwei Li

    2018-05-01

    Full Text Available The hippocampus plays an important role in memory function relying on information interaction between distributed brain areas. The hippocampus can be divided into the anterior and posterior sections with different structure and function along its long axis. The aim of this study is to investigate the effects of normal aging on the structural covariance of the anterior hippocampus (aHPC and the posterior hippocampus (pHPC. In this study, 240 healthy subjects aged 18–89 years were selected and subdivided into young (18–23 years, middle-aged (30–58 years, and older (61–89 years groups. The aHPC and pHPC was divided based on the location of uncal apex in the MNI space. Then, the structural covariance networks were constructed by examining their covariance in gray matter volumes with other brain regions. Finally, the influence of age on the structural covariance of these hippocampal sections was explored. We found that the aHPC and pHPC had different structural covariance patterns, but both of them were associated with the medial temporal lobe and insula. Moreover, both increased and decreased covariances were found with the aHPC but only increased covariance was found with the pHPC with age (p < 0.05, family-wise error corrected. These decreased connections occurred within the default mode network, while the increased connectivity mainly occurred in other memory systems that differ from the hippocampus. This study reveals different age-related influence on the structural networks of the aHPC and pHPC, providing an essential insight into the mechanisms of the hippocampus in normal aging.

  11. Modulation of [3H]-glutamate binding by serotonin in the rat hippocampus: An autoradiographic study

    International Nuclear Information System (INIS)

    Mennini, T.; Miari, A.

    1991-01-01

    Serotonin (5-HT) added in vitro increased [ 3 H]-glutamate specific binding in the rat hippocampus, reaching statistical significance in layers rich in N-Methyl-D-Aspartate sensitive glutamate receptors. This effect was explained by a significant increase in the apparent affinity of [ 3 H]-glutamate when 5-HT is added in vitro. Two days after lesion of serotonergic afferents to the hippocampus with 5,7- Dihydroxytryptamine [ 3 H]-glutamate binding was significantly decreased in the CA3 region and stratum lacunosum moleculare of the hippocampus, this reduction being reversed by in vitro addition of 10 μM 5-HT. The decrease observed is due to a significant reduction of quisqualate-insensitive (radiatum CA3) and kainate receptors (strata oriens, radiatum, pyramidal of CA3). Five days after lesion [ 3 H]-glutamate binding increased significantly in the CA3 region of the hippocampus but was not different from sham animals in the other hippocampal layers. Two weeks after lesion [ 3 H]-glutamate binding to quisqualate-insensitive receptors was increased in all the hippocampal layers, while kainate and quisqualate-sensitive receptors were not affected. These data are consistent with the possibility that 5-HT is a direct positive modulator of glutamate receptor subtypes

  12. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.

    1995-01-01

    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

  13. The investigation of biometric characteristics of seahorse species [Hippocampus hippocampus (Linnaeus,

    Directory of Open Access Journals (Sweden)

    Şule Gürkan

    2015-12-01

    Full Text Available Bu çalışma, İzmir Körfezi’nde dağılım gösteren Syngnathidae familyasına ait denizatı türlerini ve bu türlerin biyometrik özelliklerini belirlemek amacıyla yapılmıştır. Şubat 2000 tarihinde bölgede avlanan balıkçılardan 29 adet Hippocampus hippocampus, ve 200 adet Hippocampus guttulatus örneği temin edilmiştir. Elde edilen örneklerin metrik ve meristik özellikleri ve boy-ağırlık ilişkileri ile boy ve ağırlık frekans değerleri verilmiştir

  14. Orthogonal wave propagation of epileptiform activity in the planar mouse hippocampus in vitro.

    Science.gov (United States)

    Kibler, Andrew B; Durand, Dominique M

    2011-09-01

    In vitro brain preparations have been used extensively to study the generation and propagation of epileptiform activity. Transverse and longitudinal slices of the rodent hippocampus have revealed various patterns of propagation. Yet intact connections between the transverse and longitudinal pathways should generate orthogonal (both transverse and longitudinal) propagation of seizures involving the entire hippocampus. This study utilizes the planar unfolded mouse hippocampus preparation to reveal simultaneous orthogonal epileptiform propagation and to test a method of arresting propagation. This study utilized an unfolded mouse hippocampus preparation. It was chosen due to its preservation of longitudinal neuronal processes, which are thought to play an important role in epileptiform hyperexcitability. 4-Aminopyridine (4-AP), microelectrodes, and voltage-sensitive dye imaging were employed to investigate tissue excitability. In 50-μm 4-AP, stimulation of the stratum radiatum induced transverse activation of CA3 cells but also induced a longitudinal wave of activity propagating along the CA3 region at a speed of 0.09 m/s. Without stimulation, a wave originated at the temporal CA3 and propagated in a temporal-septal direction could be suppressed with glutamatergic receptor antagonists. Orthogonal propagation traveled longitudinally along the CA3 pathway, secondarily invading the CA1 region at a velocity of 0.22 ± 0.024 m/s. Moreover, a local lesion restricted to the CA3 region could arrest wave propagation. These results reveal a complex two-dimensional epileptiform wave propagation pattern in the hippocampus that is generated by a combination of synaptic transmission and axonal propagation in the CA3 recurrent network. Epileptiform propagation block via a transverse selective CA3 lesion suggests a potential surgical technique for the treatment of temporal lobe epilepsy. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. High Plasticity of New Granule Cells in the Aging Hippocampus

    Directory of Open Access Journals (Sweden)

    Mariela F. Trinchero

    2017-10-01

    Full Text Available Summary: During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity. : Trinchero et al. show that development of new granule cells born in the adult hippocampus is strongly influenced by age. In the aging hippocampus, new neurons remain immature for prolonged intervals, yet voluntary exercise triggers their rapid growth and functional synaptogenesis. This extensive structural remodeling is mediated by neurotrophins. Keywords: adult neurogenesis, dentate gyrus, functional integration, neurotrophins, synaptogenesis, exercise

  17. HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

  18. Anterior/posterior competitive deactivation/activation dichotomy in the human hippocampus as revealed by a 3D navigation task.

    Directory of Open Access Journals (Sweden)

    Isabel Catarina Duarte

    Full Text Available Anterior/posterior long axis specialization is thought to underlie the organization of the hippocampus. However it remains unclear whether antagonistic mechanisms differentially modulate processing of spatial information within the hippocampus. We used fMRI and a virtual reality 3D paradigm to study encoding and retrieval of spatial memory during active visuospatial navigation, requiring positional encoding and retrieval of object landmarks during the path. Both encoding and retrieval elicited BOLD activation of the posterior most portion of hippocampus, while concurrent deactivations (recently shown to reflect decreases in neural responses were found in the most anterior regions. Encoding elicited stronger activity in the posterior right than the left hippocampus. The former structure also showed significantly stronger activity for allocentric vs. egocentric processing during retrieval. The anterior vs. posterior pattern mimics, from a functional point, although at much distinct temporal scales, the previous anatomical findings in London taxi drivers, whereby posterior enlargement was found at the cost of an anterior decrease, and the mirror symmetric findings observed in blind people, in whom the right anterior hippocampus was found to be larger, at the cost of a smaller posterior hippocampus, as compared with sighted people. In sum, we found a functional dichotomy whereby the anterior/posterior hippocampus shows antagonistic processing patterns for spatial encoding and retrieval of 3D spatial information. To our knowledge, this is the first study reporting such a dynamical pattern in a functional study, which suggests that differential modulation of neural responses within the human hippocampus reflects distinct roles in spatial memory processing.

  19. Asymmetry of Hippocampus and Amygdala Defect in Subjective Cognitive Decline Among the Community Dwelling Chinese

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    Ling Yue

    2018-06-01

    Full Text Available Background: Subjective cognitive decline (SCD may be the first clinical sign of Alzheimer's disease (AD. SCD individuals with normal cognition may already have significant medial temporal lobe atrophy. However, few studies have been devoted to exploring the alteration of left-right asymmetry with hippocampus and amygdala in SCD. The aim of this study was to compare SCD individuals with amnestic mild cognitive impairment (MCI patients and the normal population for volume and asymmetry of hippocampus, amygdala and temporal horn, and to assess their relationship with cognitive function in elderly population living in China.Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC underwent a standard T1-weighted MRI, from which the volumes of the hippocampus and amygdala were calculated and compared. Then we evaluated the pattern and extent of asymmetry in hippocampus and amygdala of these samples. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function.Results: Among the three groups, SCD showed more depressive symptoms (p < 0.001 and higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007 than controls. In terms of brain data, significant differences were found in the volume and asymmetry of both hippocampus and amygdala among the three groups (P < 0.05. In logistic analysis controlled by age, gender, education level, depression symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking, both SCD and MCI individuals showed significant decreased right hippocampal and amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in hippocampus. Furthermore, correlation was shown between the volume of right hippocampus and right amygdala with MMSE and MoCA in SCD group.Conclusion: Our results supported

  20. Directory of Regional Centers and Educational Programs Providing Services to Deaf/Blind Children and Youth in the United States (Including Puerto Rico and the Virgin Islands).

    Science.gov (United States)

    Alonso, Lou, Comp.

    Listed in the directory are over 200 educational programs and services for deaf blind children in the United States and U. S. territories. It is noted that the 10 coordinators of regional centers for services to deaf blind children have aided in compilation of the directory. Listings are arranged by state within the New England, Mid-Atlantic…

  1. An in vivo MR spectroscopy imaging on hippocampus in patients with posttraumatic stress disorder

    International Nuclear Information System (INIS)

    Chen Shulin; Li Lingjiang; Zhang Jinlin; Ma Ning; Gao Xueping; Liu Jun; He Zhong

    2006-01-01

    Objective: To study the characteristic of in vivo MR spectroscopy (MRS) in right and left hippocampal regions of patients with posttraumatic stress disorder (PTSD). Methods: 1 H-MRS was performed on the right and left hippocampal regions in 12 patients with PTSD and 12 normal controls. The peak values of NAA, Cr, and Cho were calculated by Functool software, and the ratios of NAA/Cr and Cho/Cr were compared between PTSD and the control. Results: The NAA/Cr ratio of left hippocampal region in PTSD group was significantly lower than that in the control (F=9.99, P=0.006), but the Cho/Cr ratio in left hippocampal region had no difference between the two groups (F=0.36, P=0.55). Furthermore, the ratios of NAA/Cr and Cho/Cr in right hippocampal region had no significant difference between both groups (F=1.44, P=0.25). Demography factors and the severity of PTSD symptoms were not related to the abnormity of the NAA/Cr ratio of the left hippocampus in PTSD group. Conclusion: The pathological abnormality might exist in the left hippocampus in patients with PTSD, and the NAA/Cr ratio of the left hippocampus was lower than normal. (authors)

  2. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    Science.gov (United States)

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  3. Aeromagnetic maps of the Colorado River region including the Kingman, Needles, Salton Sea, and El Centro 1 degree by 2 degrees quadrangles, California, Arizona, and Nevada

    Science.gov (United States)

    Mariano, John; Grauch, V.J.

    1988-01-01

    Aeromagnetic data for the Colorado river region have been compiled as part of the Pacific to Arizona Crustal Experiment (PACE) Project. The data are presented here in a series of six compilations for the Kingman, Needles, Salton Sea, and El Centro 1 degree by 2 degree quadrangles, California, Arizona, and Nevada, at scales of 1:250,000 and 1:750,000. The scales and map areas are identical to those used by Mariano and others (1986) to display the Bouguer and isotatic residual gravity for this region. Data were compiled separately for the Kingman quadrangle, the Needles quadrangle, and an area covering the Salton Sea quadrangle and part of the El Centro quadrangle.

  4. Treatment of Thyroid Cancer: A Review of the Regional Experiences (including countries from Asia-Pacific, Europe, North America, Africa and Latin America)

    International Nuclear Information System (INIS)

    Howarth, D.; Nagataki, S.; Padhy, A.K.

    2006-01-01

    Radioiodine (I-131) therapy has been in use for the treatment of thyroid diseases for the past six decades. Although the use of radioiodine has been in vogue for a long time, its use in therapy for well-differentiated thyroid cancer is still controversial, varied and in many instances based on personal and institutional philosophy. The practice is also influenced by available infrastructure, national policy with regard to health, financial and human resources; as well as social, cultural and ethnic milieu of a particular region or country. The World Radiopharmaceutical Therapy Council had carried out a survey on the practice of radioiodine treatment of differentiated thyroid cancer around the world. This paper is a compilation of information from several countries/ regions around the world, which may offer insight into the practice of one of the most important and widely practiced radionuclide therapeutic procedures in clinical medicine. It is interesting to note that despite regional or national differences with regard to history, culture, finance, resources, beliefs, practices and attitude there has been more or less a universal unanimity on the 'basics' related to the practice of radioiodine therapy for differentiated thyroid cancer. (author)

  5. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Science.gov (United States)

    Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

  6. Tuning synaptic transmission in the hippocampus by stress: The CRH system

    Directory of Open Access Journals (Sweden)

    Yuncai eChen

    2012-04-01

    Full Text Available To enhance survival, an organism needs to remember--and learn from--threatening or stressful events. This fact necessitates the presence of mechanisms by which stress can influence synaptic transmission in brain regions, such as hippocampus, that subserve learning and memory. A major focus of this series of monographs is on the role and actions of adrenal-derived hormones, corticosteroids, and of brain-derived neurotransmitters, on synaptic function in the stressed hippocampus. Here we focus on the contribution of hippocampus-intrinsic, stress-activated CRH-CRH receptor signaling to the function and structure of hippocampal synapses. CRH is expressed in interneurons of adult hippocampus, and is released from axon terminals during stress. The peptide exerts time- and dose-dependent effects on learning and memory via modulation of synaptic function and plasticity. Whereas physiological levels of CRH, acting over seconds to minutes, augment memory processes, exposure to presumed severe-stress levels of the peptide results in spine retraction and loss of synapses over more protracted time-frames. Loss of dendritic spines (and hence of synapses takes place through actin cytoskeleton collapse downstream of CRHR1 receptors that reside within excitatory synapses on spine heads. Chronic exposure to stress levels of CRH may promote dying-back (atrophy of spine-carrying dendrites. Thus, the acute effects of CRH may contribute to stress-induced adaptive mechanisms, whereas chronic or excessive exposure to the peptide may promote learning problems and premature cognitive decline.

  7. Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

    Directory of Open Access Journals (Sweden)

    Luciano K. Jornada

    2012-01-01

    Full Text Available OBJECTIVE: The present study aims to investigate the effects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. METHODS: Animals received a single intracerebroventricular injection of ouabain (10-3 and 10-2 M or artificial cerebrospinal fluid and immediately, 1h, 24h, or seven days after injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group. RESULTS: When evaluated immediately, 3h, or 24h after injection, ouabain in doses of 10-2 and 10-3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days after injection, ouabain in 10-2 and 10-3 M, showed a significant reduction in BDNF levels in both brain regions evaluated. DISCUSSION: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days after administration, supporting the Na/K ATPase hypothesis for bipolar illness.

  8. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

    Science.gov (United States)

    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

    2017-08-01

    Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

  9. Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice

    Directory of Open Access Journals (Sweden)

    Zhen Zhang

    2016-01-01

    Full Text Available The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1 of hippocampus and mediodorsal thalamus (MDT in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1~5. The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1 High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2 In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

  10. Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

    Science.gov (United States)

    Dwyer, Jessica B; Janssen, Jennifer; Luckasevic, Todd M; Williams, Karl E

    2018-01-01

    Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. © 2017 American Academy of Forensic Sciences.

  11. The hippocampus as a "stupid," domain-specific module: Implications for theories of recent and remote memory, and of imagination.

    Science.gov (United States)

    Moscovitch, Morris

    2008-03-01

    The hippocampus and surrounding regions of the medial temporal lobe play a central role in all neuropsychological theories of memory. It is still a matter of debate, however, how best to characterise the functions of these regions, the hippocampus in particular. In this article, I examine the proposal that the hippocampus is a "stupid" module whose specific domain is consciously apprehended information. A number of interesting consequences for the organisation of memory and the brain follow from this proposal and the assumptions it entails. These, in turn, have important implications for neuropsychological theories of recent and remote episodic, semantic, and spatial memory and for the functions that episodic memory may serve in perception, comprehension, planning, imagination, and problem solving. I consider these implications by selectively reviewing the literature and primarily drawing on research my collaborators and I have conducted. Copyright (c) 2008 APA, all rights reserved.

  12. Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat

    International Nuclear Information System (INIS)

    Frederickson, C.J.; Klitenick, M.A.; Manton, W.I.; Kirkpatrick, J.B.

    1983-01-01

    Zinc was measured in whole hippocampus and in hippocampal sub-regions by stable-isotope dilution mass spectrometry. Lyophilized tissues were spiked by a precisely-known amount of zinc-64. The zinc-64/zinc-66 isotope ratio was determined by mass spectrometry. In both man and the rat, the most zinc (102-145 ppm, dry weight) was found in the hilar region, the least (27-35) in the fimbria. The amount of zinc directly associated with mossy-fiber axons was estimated to be approximately 8% of the total zinc in the hippocampus, and the concentration of mossy-fiber zinc was estimated at 220-300 μM. Methodological and theoretical implications of the quantitative findings were discussed. (Auth.)

  13. Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

    Science.gov (United States)

    Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

    2017-09-29

    Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

    Science.gov (United States)

    Burton, S; Murphy, D; Qureshi, U; Sutton, P; O'Keefe, J

    2000-07-15

    Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

  15. ONE PROBABLE MECHANISM OF THE LEARNING-MEMORY DAMAGE BY LEAD: THE CHANGES OF NOS IN HIPPOCAMPUS

    Institute of Scientific and Technical Information of China (English)

    王静; 赵义; 杨章民; 张进; 李积胜; 司履生; 王一理

    2003-01-01

    Objective To study the effects of lead on the activity and expression of nitric oxide synthase (NOS) and relationship between the effects of lead on learning-memory and changes of NOS in subfields of hippocampus. Methods Y-maze test was used to study the effects of lead on ability of learning-memory; NADPH-d histochemistry and immunohistochemistry methods were used to investigate the changes of NOS in subfields of hippocampus. Results Compared with the control group, the ability of learning- memory in lead-exposed rats was significantly decreased (P<0.05); the number of NOS positive neurons in CA1 region and dentate gyrus of lead-exposed rats was significantly decreased(P<0.05), but no marked changes in CA3 region; the number of nNOS positive neurons in CA1 of lead-exposed rats was also significantly decreased(P<0.05), but no obvious changes in CA3. Conclusion Lead could damage the ability of learning-memory in rats. Lead could decrease the activity and expression of NOS in hippocampus and had different effects on NOS in different subfields of hippocampus. The changes of NOS in hippocampus induced by lead may be the mechanism of the learning-memory damage by lead.

  16. Numerical investigation of a double-junction a:SiGe thin-film solar cell including the multi-trench region

    International Nuclear Information System (INIS)

    Kacha, K.; Djeffal, F.; Ferhati, H.; Arar, D.; Meguellati, M.

    2015-01-01

    We present a new approach based on the multi-trench technique to improve the electrical performances, which are the fill factor and the electrical efficiency. The key idea behind this approach is to introduce a new multi-trench region in the intrinsic layer, in order to modulate the total resistance of the solar cell. Based on 2-D numerical investigation and optimization of amorphous SiGe double-junction (a-Si:H/a-SiGe:H) thin film solar cells, in the present paper numerical models of electrical and optical parameters are developed to explain the impact of the multi-trench technique on the improvement of the double-junction solar cell electrical behavior for high performance photovoltaic applications. In this context, electrical characteristics of the proposed design are analyzed and compared with conventional amorphous silicon double-junction thin-film solar cells. (paper)

  17. SMAP Multi-Temporal Soil Moisture and Vegetation Optical Depth Retrievals in Vegetated Regions Including Higher-Order Soil-Canopy Interactions

    Science.gov (United States)

    Feldman, A.; Akbar, R.; Konings, A. G.; Piles, M.; Entekhabi, D.

    2017-12-01

    The Soil Moisture Active Passive (SMAP) mission utilizes a zeroth order radiative transfer model, known as the tau-omega model, to retrieve soil moisture from microwave brightness temperature observations. This model neglects first order scattering which is significant at L-Band in vegetated regions, or 30% of land cover. Previous higher order algorithms require extensive in-situ measurements and characterization of canopy layer physical properties. We propose a first order retrieval algorithm that approximately characterizes the eight first order emission pathways using rough surface reflectivity, vegetation optical depth (VOD), and scattering albedo terms. The recently developed Multi-Temporal Dual Channel Algorithm (MT-DCA) then retrieves these three parameters in a forward model without ancillary information under the assumption of temporally static albedo and constant vegetation water content between three day SMAP revisits. The approximated scattering terms are determined to be conservative estimates of analytically derived first order scattering terms. In addition, we find the first order algorithm to be more sensitive to surface emission than the tau-omega model. The simultaneously retrieved VOD, previously demonstrated to be proportional to vegetation water content, can provide insight into vegetation dynamics in regions with significant phenology. Specifically, dry tropical forests exhibit an increase in VOD during the dry season in alignment with prior studies that suggest that certain vegetative species green up during the dry season despite limited water availability. VOD retrieved using the first order algorithm and MT-DCA framework can therefore contribute to understanding of tropical forests' role in the carbon, energy, and water cycles, which has yet to be fully explained.

  18. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

    OpenAIRE

    Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R

    2002-01-01

    Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

  19. A larger hippocampus is associated with longer-lasting spatial memory

    OpenAIRE

    Biegler, Robert; McGregor, Anthony; Krebs, John R.; Healy, Susan D.

    2001-01-01

    Volumetric studies in a range of animals (London taxi-drivers, polygynous male voles, nest-parasitic female cowbirds, and a number of food-storing birds) have shown that the size of the hippocampus, a brain region essential to learning and memory, is correlated with tasks involving an extra demand for spatial learning and memory. In this paper, we report the quantitative advantage that food storers gain from such an enlargement. Coal tits (Parus ater) a food-storin...

  20. Late-glacial and Holocene Vegetation and Climate Variability, Including Major Droughts, in the Sky Lakes Region of Southeastern New York State

    Science.gov (United States)

    Menking, Kirsten M.; Peteet, Dorothy M.; Anderson, Roger Y.

    2012-01-01

    Sediment cores from Lakes Minnewaska and Mohonk in the Shawangunk Mountains of southeastern New York were analyzed for pollen, plantmacrofossils, macroscopic charcoal, organic carbon content, carbon isotopic composition, carbon/nitrogen ratio, and lithologic changes to determine the vegetation and landscape history of the greater Catskill Mountain region since deglaciation. Pollen stratigraphy generally matches the New England pollen zones identified by Deevey (1939) and Davis (1969), with boreal genera (Picea, Abies) present during the late Pleistocene yielding to a mixed Pinus, Quercus and Tsuga forest in the early Holocene. Lake Minnewaska sediments record the Younger Dryas and possibly the 8.2 cal kyr BP climatic events in pollen and sediment chemistry along with an 1400 cal yr interval of wet conditions (increasing Tsuga and declining Quercus) centered about 6400 cal yr BP. BothMinnewaska andMohonk reveal a protracted drought interval in themiddle Holocene, 5700-4100 cal yr BP, during which Pinus rigida colonized the watershed, lake levels fell, and frequent fires led to enhanced hillslope erosion. Together, the records show at least three wet-dry cycles throughout the Holocene and both similarities and differences to climate records in New England and central New York. Drought intervals raise concerns for water resources in the New York City metropolitan area and may reflect a combination of enhanced La Niña, negative phase NAO, and positive phase PNA climatic patterns and/or northward shifts of storm tracks.

  1. Study of the variations in apoptotic factors in hippocampus of male rats with posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Behrang Alani

    2013-01-01

    Full Text Available Background: Post-traumatic stress disorder (PTSD is a stress-related psychosomatic disorder caused by occurrence of a traumatic event and the hippocampus volume of the patients with Post-traumatic stress disorder decreased. However, the mechanisms that cause such damage are not well-understood. The aim of this study is to detect the expression of apoptosis-related Bax, Bcl-2, Caspase-3 and Insulin-like growth Factor-I proteins in the hippocampus region in the Predatory stress rats. Materials and Methods: A total of 70 male wistar rats were divided into Predatory stress groups of 1d, 2d, 3d, 7d, 14d, 30d and a normal control group (N = 10. Rats were subjected to 5 min of predatory stress and then exposed to the elevated plus-maze (EPM. Serum corticosterone and Insulin-like growth factor-1 level of Hippocampus were measured by ELISA technique. The expression of Bax, Bcl-2, and Caspase-3 were detected by western blotting. Results: Rats spent significantly more time in closed arms of the elevated plus maze (EPM than control group after exposure to stress. Serum levels of corticosterone significantly increased at 2d-3d. The expression of hippocampal IGF-1 was significantly up-regulated at 1d-2d after stress. Both Bax and the ratio of Bax/Bcl-2 significantly peaked at Predatory stress 2d-14d. Caspase3 was significantly active among 2d-30 compared to the normal control. Conclusion: The activation of caspase-3 in the stress groups indicates that apoptosis may be one of the reasons inducing hippocampus atrophy and play roles in the pathogenesis of PTSD. Increase in hippocampus levels of IGF-1 during early PTSD might be involved in the early molecular inhibitory mechanism of apoptosis in PTSD.

  2. The Insulin Regulatory Network in Adult Hippocampus and Pancreatic Endocrine System

    Directory of Open Access Journals (Sweden)

    Masanao Machida

    2012-01-01

    Full Text Available There is a very strong correlation between the insulin-mediated regulatory system of the central nervous system and the pancreatic endocrine system. There are many examples of the same transcriptional factors being expressed in both regions in their embryonic development stages. Hormonal signals from the pancreatic islets influence the regulation of energy homeostasis by the brain, and the brain in turn influences the secretions of the islets. Diabetes induces neuronal death in different regions of the brain especially hippocampus, causes alterations on the neuronal circuits and therefore impairs learning and memory, for which the hippocampus is responsible. The hippocampus is a region of the brain where steady neurogenesis continues throughout life. Adult neurogenesis from undifferentiated neural stem cells is greatly decreased in diabetic patients, and as a result their learning and memory functions decline. Might it be possible to reactivate stem cells whose functions have deteriorated and that are present in the tissues in which the lesions occur in diabetes, a lifestyle disease, which plagues modern humans and develops as a result of the behavior of insulin-related factor? In this paper we summarize research in regard to these matters based on examples in recent years.

  3. Hippocampus and amygdala volumes in patients with vaginismus.

    Science.gov (United States)

    Atmaca, Murad; Baykara, Sema; Ozer, Omer; Korkmaz, Sevda; Akaslan, Unsal; Yildirim, Hanefi

    2016-06-22

    To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition.

  4. Distinct roles of the hippocampus and perirhinal cortex in GABAA receptor blockade-induced enhancement of object recognition memory.

    Science.gov (United States)

    Kim, Jong Min; Kim, Dong Hyun; Lee, Younghwan; Park, Se Jin; Ryu, Jong Hoon

    2014-03-13

    It is well known that the hippocampus plays a role in spatial and contextual memory, and that spatial information is tightly regulated by the hippocampus. However, it is still highly controversial whether the hippocampus plays a role in object recognition memory. In a pilot study, the administration of bicuculline, a GABAA receptor antagonist, enhanced memory in the passive avoidance task, but not in the novel object recognition task. In the present study, we hypothesized that these different results are related to the characteristics of each task and the different roles of hippocampus and perirhinal cortex. A region-specific drug-treatment model was employed to clarify the role of the hippocampus and perirhinal cortex in object recognition memory. After a single habituation in the novel object recognition task, intra-perirhinal cortical injection of bicuculline increased and intra-hippocampal injection decreased the exploration time ratio to novel object. In addition, when animals were repeatedly habituated to the context, intra-perirhinal cortical administration of bicuculline still increased exploration time ratio to novel object, but the effect of intra-hippocampal administration disappeared. Concurrent increases of c-Fos expression and ERK phosphorylation were observed in the perirhinal cortex of the object with context-exposed group either after single or repeated habituation to the context, but no changes were noted in the hippocampus. Altogether, these results suggest that object recognition memory formation requires the perirhinal cortex but not the hippocampus, and that hippocampal activation interferes with object recognition memory by the information encoding of unfamiliar environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

    Science.gov (United States)

    Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

    2017-08-03

    Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

  6. Mitochondria morphologic changes and metabolic effects of rat hippocampus after microwave irradiation

    International Nuclear Information System (INIS)

    Zhao Li; Peng Ruiyun; Gao Yabing; Wang Shuiming; Wang Lifeng; Dong Qi; Xu Xinping; Ma Junjie

    2007-01-01

    Objective: To investigate the effect of microwave on mitochondria morphologic and metabolism of rat hippocampus. Methods: 30 male rats were exposed to microwave with the average power density of 30 mW/cm 2 . Rats were sacrificed at 6 h, 1 d, 3 d and 7 d after irradiation. Electron microscope, enzymatic activity staining and spectrophotometer were used to study ultrastructure change of hippocampus mitochondria and activity of ATPase, SDH and MAO. Mitochondrial ATP, ADP and AMP contents were measured by high performance liquid chromatography (HPLC). Results: At 6 h after microwave radiation, the sizes and shapes of hippocampus mitochondria were abnormal and the injury of mitochondria was aggravated at 1 and 3 d after radiation. The mitochondria presented swell, cavitation including disorder, shortness and decrease of crest. The activity of SDH and content of ATP were decreased at 6 h, most serious at 3 d(P<0.01), and recovered at 7 d after radiation. The activity of ATPase and MAO increased notably at 1 d and 3 d after radiation (P<0.01). Conclusions: Microwave can damage the structure and function of mitochondria in rat hippocampus, and cause the energy metabolism of enzyme disorder. (authors)

  7. Changes in free and bound water in the hippocampus of patients with Alzheimer's disease

    International Nuclear Information System (INIS)

    Asano, Tetsuichi; Hanyu, Haruo

    2000-01-01

    We measured the T2 relaxation time using dual spin echo MRI, and also the magnetization transfer ratio (MTR) using gradient echo MRI, in the hippocampus of Alzheimer's disease (AD) patients, and compared these factors to those of non-Alzheimer's dementia (non-AD) patients and of control subjects. The degree of medial temporal lobe atrophy in AD patients was similar to that of non-AD patients, although atrophy was more severe in AD and non-AD patients than in the control group. MTRs in the hippocampus were significantly lower in AD patients than in non-AD patients and in the control group. No significant differences in the T2 values of the three groups were found. The change of T2 x (1-MTR/100) in the hippocampus was significantly higher in AD patients than in non-AD patients and the control group and the change of T2 x MTR/100 was significantly lower in AD patients than in non-AD patients and the control group. Significant correlations between MMSE scores and MR parameters were found in AD patients, but not in non-AD patients. These results suggest that a decrease in the MTR in the hippocampus of AD, probably due to a decrease in bound water and an increase in free water, reflects underlying pathological changes which include a loss of neurons and gliosis. (author)

  8. Lack of association of the serotonin transporter gene promoter region polymorphism, 5-HTTLPR, including rs25531 with cigarette smoking and alcohol consumption

    DEFF Research Database (Denmark)

    Rasmussen, Henrik; Bagger, Yu; Tanko, Laszlo B

    2009-01-01

    We addressed the question whether 5-HTTLPR, a variable number of tandem repeats located in the 5' end of the serotonin transporter gene, is associated with smoking or alcohol consumption. Samples of DNA from 1,365 elderly women with a mean age of 69.2 years were genotyped for this polymorphism...... using a procedure, which allowed the simultaneous determination of variation in the number of repeat units and single nucleotide changes, including the A > G variation at rs25531 for discrimination between the L(A) and L(G) alleles. Qualitative and quantitative information on the women's current...... and previous consumption of cigarettes and alcohol were obtained using a questionnaire. Genotypes were classified according to allele size, that is, S and L with 14 and 16 repeat units, respectively, and on a functional basis by amalgamation of the L(G) and S alleles. Data were subjected to regression analyses...

  9. Resistance exercise improves hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    R.C. Cassilhas

    2012-12-01

    Full Text Available It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R, which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group: control, SHAM, and resistance exercise (RES. The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA, the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05. Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

  10. Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.

    Science.gov (United States)

    Curtis, J M R; Santos, S V; Nadeau, J L; Gunn, B; Bigney Wilner, K; Balasubramanian, H; Overington, S; Lesage, C-M; D'entremont, J; Wieckowski, K

    2017-12-01

    To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m -2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (L S ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m 2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L ∞  = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment. © 2017 The Fisheries Society of the British Isles.

  11. Deformation integrity monitoring for GNSS positioning services including local, regional and large scale hazard monitoring - the Karlsruhe approach and software(MONIKA)

    Science.gov (United States)

    Jaeger, R.

    2007-05-01

    GNSS-positioning services like SAPOS/ascos in Germany and many others in Europe, America and worldwide, usually yield in a short time their interdisciplinary and country-wide use for precise geo-referencing, replacing traditional low order geodetic networks. So it becomes necessary that possible changes of the reference stations' coordinates are detected ad hoc. The GNSS-reference-station MONitoring by the KArlsruhe approach and software (MONIKA) are designed for that task. The developments at Karlsruhe University of Applied Sciences in cooperation with the State Survey of Baden-Württemberg are further motivated by a the official resolution of the German state survey departments' association (Arbeitsgemeinschaft der Vermessungsverwaltungen Deutschland (AdV)) 2006 on coordinate monitoring as a quality-control duty of the GNSS-positioning service provider. The presented approach can - besides the coordinate control of GNSS-positioning services - also be used to set up any GNSS-service for the tasks of an area-wide geodynamical and natural disaster-prevention service. The mathematical model of approach, which enables a multivariate and multi-epochal design approach, is based on the GNSS-observations input of the RINEX-data of the GNSS service, followed by fully automatic processing of baselines and/or session, and a near-online setting up of epoch-state vectors and their covariance-matrices in a rigorous 3D network adjustment. In case of large scale and long-term monitoring situations, geodynamical standard trends (datum-drift, plate-movements etc.) are accordingly considered and included in the mathematical model of MONIKA. The coordinate-based deformation monitoring approach, as third step of the stepwise adjustments, is based on the above epoch-state vectors, and - splitting off geodynamics trends - hereby on a multivariate and multi-epochal congruency testing. So far, that no other information exists, all points are assumed as being stable and congruent reference

  12. A genome wide association study for backfat thickness in Italian Large White pigs highlights new regions affecting fat deposition including neuronal genes

    Directory of Open Access Journals (Sweden)

    Fontanesi Luca

    2012-11-01

    Full Text Available Abstract Background Carcass fatness is an important trait in most pig breeding programs. Following market requests, breeding plans for fresh pork consumption are usually designed to reduce carcass fat content and increase lean meat deposition. However, the Italian pig industry is mainly devoted to the production of Protected Designation of Origin dry cured hams: pigs are slaughtered at around 160 kg of live weight and the breeding goal aims at maintaining fat coverage, measured as backfat thickness to avoid excessive desiccation of the hams. This objective has shaped the genetic pool of Italian heavy pig breeds for a few decades. In this study we applied a selective genotyping approach within a population of ~ 12,000 performance tested Italian Large White pigs. Within this population, we selectively genotyped 304 pigs with extreme and divergent backfat thickness estimated breeding value by the Illumina PorcineSNP60 BeadChip and performed a genome wide association study to identify loci associated to this trait. Results We identified 4 single nucleotide polymorphisms with P≤5.0E-07 and additional 119 ones with 5.0E-07 Conclusions Further investigations are needed to evaluate the effects of the identified single nucleotide polymorphisms associated with backfat thickness on other traits as a pre-requisite for practical applications in breeding programs. Reported results could improve our understanding of the biology of fat metabolism and deposition that could also be relevant for other mammalian species including humans, confirming the role of neuronal genes on obesity.

  13. Transient global amnesia: increased signal intensity in the right hippocampus on diffusion-weighted magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, M.; Sakamoto, S.; Ishii, K. [Division of Neuroimaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders (Japan); Imamura, T.; Kazui, H.; Mori, E. [Division of Clinical Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders, Hyogo (Japan)

    2002-03-01

    We report on a patient with pure transient global amnesia (TGA) whose magnetic resonance imaging (MRI) demonstrated a small region of increased signal intensity in the right hippocampus on diffusion-weighted imaging (DWI). DWI was sensitive and useful for evaluating the early stage of TGA and might help to explain the pathophysiology of TGA. (orig.)

  14. Transient global amnesia: increased signal intensity in the right hippocampus on diffusion-weighted magnetic resonance imaging

    International Nuclear Information System (INIS)

    Matsui, M.; Sakamoto, S.; Ishii, K.; Imamura, T.; Kazui, H.; Mori, E.

    2002-01-01

    We report on a patient with pure transient global amnesia (TGA) whose magnetic resonance imaging (MRI) demonstrated a small region of increased signal intensity in the right hippocampus on diffusion-weighted imaging (DWI). DWI was sensitive and useful for evaluating the early stage of TGA and might help to explain the pathophysiology of TGA. (orig.)

  15. New records of the Japanese seahorse Hippocampus mohnikei in Southeast Asia lead to updates in range, habitat and threats.

    Science.gov (United States)

    Aylesworth, L; Lawson, J M; Laksanawimol, P; Ferber, P; Loh, T-L

    2016-04-01

    New records of the Japanese seahorse Hippocampus mohnikei from Cambodia, Malaysia, Thailand and Vietnam, along with recently published studies from India and Singapore, have greatly expanded the known range of H. mohnikei within Southeast Asia. These new records reveal novel habitat preferences and threats to H. mohnikei in the region. Although the global conservation status of H. mohnikei is classified as Data Deficient according to the IUCN Red List of Threatened Species, new sightings indicate that this species is found in similar habitats and faces similar threats as other Hippocampus species that are considered Vulnerable. © 2016 The Fisheries Society of the British Isles.

  16. Molecular and Parasitological Survey of Bovine Piroplasms in the Black Sea Region, Including the First Report of Babesiosis Associated with Babesia divergens in Turkey.

    Science.gov (United States)

    Aktas, M; Ozubek, S

    2015-11-01

    Clinical cases of babesiosis were evaluated, and the frequency of bovine Babesia and Theileria parasites was determined in cattle. Blood samples and thin blood smears were collected from 23 cattle exhibiting clinical signs of babesiosis. In addition, tick and blood samples were collected from 100 apparently healthy cattle cograzing from the same area. Egg masses obtained from fully engorged female ticks were included. DNA isolated from blood and tick samples was screened for Babesia and Theileria by reverse line blot assay. Piroplasms compatible with Babesia spp. were observed microscopically for symptomatic cattle as circular, oval, elongated, or pear-shaped bodies. Parasitemia ranged from 0.08 to 0.9% for Babesia bovis, 2.5 to 15.4% for Babesia bigemina, and 7.4% for Babesia divergens. Reverse line blot showed positivity in 13 (13%) of the sampled clinically normal cattle and revealed the presence of three Babesia species. Babesia bovis was the most prevalent (9/100, 9%), followed by Babesia occultans (3/100, 3%) and B. bigemina (1/100, 1%). One animal infected with B. bigemina was also infected with B. bovis. The single animal infected with B. divergens showed symptoms of babesiosis. Ticks were identified as Rhipicephalus annulatus, Rhipicephalus turanicus, and Ixodes ricinus. One female R. annulatus and its egg mass were infected with B. bigemina. Neither Theileria annulata nor Theileria buffeli/orientalis infections were observed in cattle or ticks. This is the first report of clinical babesiosis caused by B. divergens in cattle from Turkey. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein

    Directory of Open Access Journals (Sweden)

    Deussing Jan M

    2010-10-01

    Full Text Available Abstract Background The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure. Gene expression and regulation was determined by microarray analyses and further evaluated by bioinformatics tools including pathway and cluster analyses. Results Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN, 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains. Our search for connections between the regulated genes resulted in potential novel signalling pathways in stress. In particular, Guanine nucleotide binding protein, alpha inhibiting 2 (GNAi2 and Amyloid β (A4 precursor protein (APP were detected as stress-regulated genes, and together with other genes, seem to be integrated into stress-responsive pathways and gene networks in the PVN. Conclusions This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain.

  18. Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René

    2014-01-01

    , injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined r....... Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala......AAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests...

  19. Transient inactivation of the ventral hippocampus in neonatal rats impairs the mesolimbic regulation of prefrontal glutamate release in adulthood

    DEFF Research Database (Denmark)

    Bortz, D M; Jørgensen, Christinna Vangsgaard; Mikkelsen, J D

    2014-01-01

    Cognitive deficits in schizophrenia (SZ) reflect maturational disruptions within a neural system that includes the ventral hippocampus (VH), nucleus accumbens (NAc), basal forebrain, and prefrontal cortex (PFC). A better understanding of these changes may reveal drug targets for more efficacious ...

  20. Spatial olfactory learning facilitates long-term depression in the hippocampus.

    Science.gov (United States)

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2013-10-01

    Recently, it has emerged that visual spatial exploration facilitates synaptic plasticity at different synapses within the trisynaptic network. Particularly striking is the finding that visuospatial contexts facilitate hippocampal long-term depression (LTD), raising the possibility that this form of plasticity may be important for memory formation. It is not known whether other sensory modalities elicit similar permissive effects on LTD. Here, we explored if spatial olfactory learning facilitates LTD in the hippocampus region of freely behaving rats. Patterned afferent stimulation of the Schaffer collaterals elicited short-term depression (STD) (<1 h) of evoked responses in the Stratum radiatum of the CA1 region. Coupling of this protocol with novel exploration of a spatial constellation of olfactory cues facilitated short-term depression into LTD that lasted for over 24 h. Facilitation of LTD did not occur when animals were re-exposed 1 week later to the same odors in the same spatial constellation. Evaluation of learning behavior revealed that 1 week after the 1st odor exposure, the animals remembered the odors and their relative positions. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to facilitate LTD and to generate spatial representations. The data also support that a tight relationship exists between the processing of spatial contextual information and the expression of LTD in the hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  1. The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.

    Science.gov (United States)

    Koenig, Katherine A; Rao, Stephen M; Lowe, Mark J; Lin, Jian; Sakaie, Ken E; Stone, Lael; Bermel, Robert A; Trapp, Bruce D; Phillips, Micheal D

    2018-03-01

    Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory. Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p episodic memory loss in patients with MS.

  2. The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

    Directory of Open Access Journals (Sweden)

    Regina A. Weilbächer

    2016-12-01

    Full Text Available Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

  3. Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

    Science.gov (United States)

    Murtuza, Mohammad I; Isokawa, Masako

    2018-01-01

    Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

  4. Acutely increasing δGABA(A) receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus.

    Science.gov (United States)

    Whissell, Paul D; Eng, Dave; Lecker, Irene; Martin, Loren J; Wang, Dian-Shi; Orser, Beverley A

    2013-01-01

    Extrasynaptic γ-aminobutyric acid type A (GABA(A)) receptors that contain the δ subunit (δGABA(A) receptors) are expressed in several brain regions including the dentate gyrus (DG) and CA1 subfields of the hippocampus. Drugs that increase δGABA(A) receptor activity have been proposed as treatments for a variety of disorders including insomnia, epilepsy and chronic pain. Also, long-term pretreatment with the δGABA(A) receptor-preferring agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) enhances discrimination memory and increases neurogenesis in the DG. Despite the potential therapeutic benefits of such treatments, the effects of acutely increasing δGABA(A) receptor activity on memory behaviors remain unknown. Here, we studied the effects of THIP (4 mg/kg, i.p.) on memory performance in wild-type (WT) and δGABA(A) receptor null mutant (Gabrd(-/-)) mice. Additionally, the effects of THIP on long-term potentiation (LTP), a molecular correlate of memory, were studied within the DG and CA1 subfields of the hippocampus using electrophysiological recordings of field potentials in hippocampal slices. The results showed that THIP impaired performance in the Morris water maze, contextual fear conditioning and object recognition tasks in WT mice but not Gabrd(-/-) mice. Furthermore, THIP inhibited LTP in hippocampal slices from WT but not Gabrd(-/-) mice, an effect that was blocked by GABA(A) receptor antagonist bicuculline. Thus, acutely increasing δGABA(A) receptor activity impairs memory behaviors and inhibits synaptic plasticity. These results have important implications for the development of therapies aimed at increasing δGABA(A) receptor activity.

  5. Role of the hippocampus in memory functioning: modern view

    Directory of Open Access Journals (Sweden)

    D. O. Assonov

    2017-12-01

    Full Text Available The purpose of this review was to develop the comprehensive conception of the hippocampus role in the functioning of human memory, based on data obtained by analysis of the latest scientific literature on the topic and make recommendations for further ways of researches in this topic. The scientific literature of the last 5 years on the role of the hippocampus in memory functioning was analyzed. Based on the reviewed literature, we made the next conclusions: the hippocampus is an extremely important for memory structure with various connections for different types of memory; the hippocampus is affected by a variety of substances, most studied now are glucocorticosteroids, whose effect on memory differs depending on the start time of action; the hippocampus volume in mental disorders affecting memory is less than normal, which makes it an important diagnostic criterion; at the moment, various promising methods that can help in the therapy of PTSD, depression, phobias and other disorders associated with memory impairment and based on the knowledge of the hippocampus for the treatment of memory disorders are being developed. Based on these conclusions and data, which were analyzed, we offered the following recommendations: to implement the hippocampal function examination in the diagnostics of mental disorders, which are accompanied by a violation of its work; to use the size of the hippocampus as one of the prognostic factors for the severity of the memory-associated disorders and the therapy progress; to carefully investigate the difference in the effect of various psychotherapies and pharmacotherapies on the hippocampus to determine exactly which of the therapies is the most morphologically reasonable; to find out how significant the decrease in the hippocampal volume is for the memory functioning; to use pathogenetically and morphologically based methods to improve the function of the hippocampus in the treatment of disorders that are

  6. Visualization of Functional Neuropeptide Y Receptors in the Mouse Hippocampus and Neocortex Using [35S]GTPγS Binding

    DEFF Research Database (Denmark)

    Elbrønd-Bek, Heidi; Gøtzsche, Casper René; Skinbjerg, Mette

    2015-01-01

    The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various pathophysio......The peptide transmitter neuropeptide Y (NPY) has been implicated in a plethora of actions in the central nervous system, including the hippocampus and neocortex (NeoCx). Previous studies using traditional receptor autoradiography show that NPY receptor binding is altered under various...

  7. Imaging the dorsal hippocampus: light reflectance relationships to electroencephalographic patterns during sleep

    DEFF Research Database (Denmark)

    Rector, D M; Poe, G R; Kristensen, Morten Pilgaard

    1995-01-01

    We assessed the correspondence of 660 nm light reflectance changes from the dorsal hippocampus with slow wave electroencephalographic (EEG) activity during quiet sleep (QS) and rapid eye movement (REM) sleep in four cats. An optic probe, attached to a charge-coupled-device (CCD) video camera...... as EEG changes. Dividing the image into 10 subregions revealed that reflectance changes at the rhythmical slow wave activity band (RSA, 4-6 Hz) persisted in localized regions during QS and REM sleep, but regional changes showed considerable wave-by-wave independence between areas and from slow wave...

  8. Development of a sophisticated information system including a metadatabase and regional radioecological cadastres for assessment of the radiation impact on the environment and population of the Northwest Russia and Krasnoyarsk Region

    Energy Technology Data Exchange (ETDEWEB)

    Iskra, A.A.; Burykin, A.A. [All-Russia Research Institute of Chemical Technology (Russian Federation); Lebedev, O.G.; Popov, V.K.; Churaev, R.S. [Russian Research Center Kurchatov Institute (Russian Federation)

    2004-07-01

    The goal of the 'Radinfo' project is creation of a meta-database (MDB) and radioecological cadastres, geo-referenced information systems being a basic component of those ones, and conducting (using those systems) evaluation study of possible pathways of radionuclides from the radiation-hazardous objects, radioactive waste, and contaminated areas, followed by the ranking of threats, for two priority regions of Russia selected on the basis of expert interrogation: the North-West of Russia and Krasnoyarsk region. In order to achieve the goal the following investigation tools are being created and/or applied for evaluation study on the two regions: - information data files (local databases, publications etc.) on radiation sources, radioactive waste, and contaminated areas, as well as on the environment characteristics in the studied regions; - radionuclide transfer pathways models; - sets of local geo-information systems (comprising a basic component of GIS cadastres), embracing (scanning) the areas of two regions of interest and allowing to assess the dynamics of real and probable migration of radionuclides. The RadInfo MDB development is based on use of multi-level architecture of the Web-technologies. The multi-level architecture, unlike that of conventional 'Client-Server' type, provides more versatility and scalability. In this particular case a three-level version is realized. A SQL-server (MySQL) is used as a database server. The well-known Apache Web-server is used as an application server. For its part it provides execution of scripts in the PHP language (the scripts are program extension of the server part)With such kind of configuration there is no need in using special software on the client side. Any browser (for instance, Microsoft Internet Explorer or Netscape Navigator) can be used as a workplace. The configuration is very simple as far as as its installation, adjustment and use are concerned. The meta-database and the models of

  9. Development of a sophisticated information system including a metadatabase and regional radioecological cadastres for assessment of the radiation impact on the environment and population of the Northwest Russia and Krasnoyarsk Region

    International Nuclear Information System (INIS)

    Iskra, A.A.; Burykin, A.A.; Lebedev, O.G.; Popov, V.K.; Churaev, R.S.

    2004-01-01

    The goal of the 'Radinfo' project is creation of a meta-database (MDB) and radioecological cadastres, geo-referenced information systems being a basic component of those ones, and conducting (using those systems) evaluation study of possible pathways of radionuclides from the radiation-hazardous objects, radioactive waste, and contaminated areas, followed by the ranking of threats, for two priority regions of Russia selected on the basis of expert interrogation: the North-West of Russia and Krasnoyarsk region. In order to achieve the goal the following investigation tools are being created and/or applied for evaluation study on the two regions: - information data files (local databases, publications etc.) on radiation sources, radioactive waste, and contaminated areas, as well as on the environment characteristics in the studied regions; - radionuclide transfer pathways models; - sets of local geo-information systems (comprising a basic component of GIS cadastres), embracing (scanning) the areas of two regions of interest and allowing to assess the dynamics of real and probable migration of radionuclides. The RadInfo MDB development is based on use of multi-level architecture of the Web-technologies. The multi-level architecture, unlike that of conventional 'Client-Server' type, provides more versatility and scalability. In this particular case a three-level version is realized. A SQL-server (MySQL) is used as a database server. The well-known Apache Web-server is used as an application server. For its part it provides execution of scripts in the PHP language (the scripts are program extension of the server part)With such kind of configuration there is no need in using special software on the client side. Any browser (for instance, Microsoft Internet Explorer or Netscape Navigator) can be used as a workplace. The configuration is very simple as far as as its installation, adjustment and use are concerned. The meta-database and the models of radionuclide transfer

  10. Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice.

    Science.gov (United States)

    Brzozowska, Natalia I; Smith, Kristie L; Zhou, Cilla; Waters, Peter M; Cavalcante, Ligia Menezes; Abelev, Sarah V; Kuligowski, Michael; Clarke, David J; Todd, Stephanie M; Arnold, Jonathon C

    2017-10-01

    P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors. Female P-gp knockout mice displayed an unusual, frantic anxiety response to intraperitoneal injection stress in the light-dark test. They also tended to display reduced conditioned fear responses compared to wild-type (WT) mice in a paradigm where a single electric foot-shock stressor was paired to a context. Foot-shock stress reduced social interaction and decreased microglia cell density in the amygdala which was not varied by P-gp genotype. Independently of stressor exposure, female P-gp deficient mice displayed increased depression-like behavior, idiosyncratic darting behavior, age-related social withdrawal and hyperactivity, facilitated sensorimotor gating and altered startle reactivity. In addition, P-gp deletion increased microglia cell density in the CA3 region of the hippocampus, and the microglial cells exhibited a reactive, hypo-ramified morphology. Further, female P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the hippocampus. In conclusion, this research shows that germline P-gp deletion affected various behaviors of relevance to psychiatric conditions, and that altered microglial cell activity and enhanced GR expression in the hippocampus may play a role in mediating these behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Kinematics of suction feeding in the seahorse Hippocampus reidi.

    Science.gov (United States)

    Roos, Gert; Van Wassenbergh, Sam; Herrel, Anthony; Aerts, Peter

    2009-11-01

    Fish typically use a rostro-caudal wave of head expansion to generate suction, which is assumed to cause a uni-directional, anterior-to-posterior flow of water in the expanding head. However, compared with typical fish, syngnathid fishes have a remarkably different morphology (elongated snout, small hyoid, immobile pectoral girdle) and feeding strategy (pivot feeding: bringing the small mouth rapidly close to the prey by neurocranial dorsorotation). As a result, it is unclear how suction is generated in Syngnathidae. In this study, lateral and ventral expansions of the head were quantified in Hippocampus reidi and linked to the kinematics of the mouth, hyoid and neurocranium. In addition, the flow velocities inside the bucco-pharyngeal cavity and in front of the mouth were calculated. Our data suggest that the volume changes caused by lateral expansion are dominant over ventral expansion. Maximum gape, neurocranium rotation and hyoid depression are all reached before actual volume increase and before visible prey movement. This implies that, unlike previously studied teleosts, hyoid rotation does not contribute to ventral expansion by lowering the floor of the mouth during prey capture in H. reidi. The lateral volume changes show a rostro-caudal expansion, but the maximal flow velocity is not near the mouth aperture (as has been demonstrated for example in catfish) but at the narrow region of the buccal cavity, dorsal to the hyoid.

  12. Longitudinal association between hippocampus atrophy and episodic-memory decline.

    Science.gov (United States)

    Gorbach, Tetiana; Pudas, Sara; Lundquist, Anders; Orädd, Greger; Josefsson, Maria; Salami, Alireza; de Luna, Xavier; Nyberg, Lars

    2017-03-01

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Differential effects of centrally-active antihypertensives on 5-HT1A receptors in rat dorso-lateral septum, rat hippocampus and guinea-pig hippocampus.

    Science.gov (United States)

    Leishman, D J; Boeijinga, P H; Galvan, M

    1994-01-01

    1. The electrophysiological responses elicited by 5-hydroxytryptamine1A-(5-HT1A) receptor agonists in rat and guinea-pig CA1 pyramidal neurones and rat dorso-lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2. In the presence of 1 microM tetrodotoxin (TTX), to prevent indirect effects, 5-HT, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) hyperpolarized the neurones from rat and guinea-pig brain. 3. The hypotensive drug flesinoxan, a selective 5-HT1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5-HT1A-receptors, 5-methyl-urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4. In guinea-pig hippocampal neurones, 5-methyl-urapidil behaved as a 5-HT1A-receptor antagonist. 5. The relative efficacies (5-HT = 1) of DP-5-CT, 8-OH-DPAT, flesinoxan and 5-methyl-urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea-pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6. It is concluded that the hypotensive agents flesinoxan and 5-methyl-urapidil appear to have different efficacies at 5-HT1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated.

  14. Somatostatin receptors in rat hippocampus: localization to intrinsic neurons

    International Nuclear Information System (INIS)

    Palacios, J.M.; Reubi, J.C.; Maurer, R.

    1986-01-01

    The effect of neurotoxic chemical and electrolytical lesions on somatostatin (SS) receptor binding in the septo-hippocampal afferents, pyramidal and granule cells of the rat hippocampus was examined by autoradiography using the stable SS analogue 125 I-204-090 as radioligand. Electrolytical lesions of the septum did not result in modification of SS binding in the hippocampus. In contrast, both granule cell lesion with colchicine and pyramidal or pyramidal and granule cell lesions with increasing kainic acid doses did result in a specific decrease of binding in the dentate gyrus and hippocampus (CA 1 and CA 3 ). These results suggest that SS receptors in the hippocampus are probably associated with elements from intrinsic neurons. (Author)

  15. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Bansal, Ravi; Zhu, Hongtu

    2006-01-01

    CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology...... of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63...... healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P

  16. Role of the hippocampus in contextual modulation of fear extinction

    Institute of Scientific and Technical Information of China (English)

    Lingzhi Kong; Xihong Wu; Liang Li

    2008-01-01

    Fear extinction is an important form of emotional learning, and affects neural plasticity. Cue fear extinction is a classical form of inhibitory learning that can be used as an exposure-based treatment for phobia, because the long-term extinction memory produced during cue fear extinction can limit the over-expression of fear. The expression of this inhibitory memory partly depends on the context in which the extinction learning occurs. Studies such as transient inhibition, electrophysiology and brain imaging have proved that the hippocampus - an important structure in the limbic system - facilitates memory retrieval by contextual cues.Mediation of the hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this process.This article has reviewed the role of the hippocampus in the learning and retrieval of fear extinction.Contextual modulation of fear extinction may rely on a neural network consisting of the hippocampus, the medial prefrontal cortex and the amygdala.

  17. [Effect of electromagnetic radiation on discharge activity of neurons in the hippocampus CA1 in rats].

    Science.gov (United States)

    Tong, Jun; Chen, Su; Liu, Xiang-Ming; Hao, Dong-Mei

    2013-09-01

    In order to explore effect of electromagnetic radiation on learning and memory ability of hippocampus neuron in rats, the changes in discharge patterns and overall electrical activity of hippocampus neuron after electromagnetic radiation were observed. Rat neurons discharge was recorded with glass electrode extracellular recording technology and a polygraph respectively. Radiation frequency of electromagnetic wave was 900 MHZ and the power was 10 W/m2. In glass electrode extracellular recording, the rats were separately irradiated for 10, 20, 30, 40, 50 and 60 min, every points repeated 10 times and updated interval of 1h, observing the changes in neuron discharge and spontaneous discharge patterns after electromagnetic radiation. In polygraph recording experiments, irradiation group rats for five days a week, 6 hours per day, repeatedly for 10 weeks, memory electrical changes in control group and irradiation group rats when they were feeding were repeatedly monitored by the implanted electrodes, observing the changes in peak electric digits and the largest amplitude in hippocampal CA1 area, and taking some electromagnetic radiation sampling sequence for correlation analysis. (1) Electromagnetic radiation had an inhibitory role on discharge frequency of the hippocampus CA1 region neurons. After electromagnetic radiation, discharge frequency of the hippocampus CA1 region neurons was reduced, but the changes in scale was not obvious. (2) Electromagnetic radiation might change the spontaneous discharge patterns of hippocampus CA1 region neurons, which made the explosive discharge pattern increased obviously. (3) Peak potential total number within 5 min in irradiation group was significantly reduced, the largest amplitude was less than that of control group. (4) Using mathematical method to make the correlation analysis of the electromagnetic radiation sampling sequence, that of irradiation group was less than that of control group, indicating that there was a tending

  18. Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2

    Science.gov (United States)

    2007-10-24

    embryological and developmental or a result of later problems. Delays in prenatal growth of the Ts65Dn cerebral cortex and hippocampus due to longer...cultured from both DS patients and model animals are also reportedly more vulnerable to apoptosis (Sawa, 1999). A majority of research investigating cell...death in DS has been limited to several apoptosis -related genes, including those related to oxidative stress, and transcription factors overexpressed

  19. Hippocampus, delay discounting, and vicarious trial-and-error.

    Science.gov (United States)

    Bett, David; Murdoch, Lauren H; Wood, Emma R; Dudchenko, Paul A

    2015-05-01

    In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude. © 2014 Wiley Periodicals, Inc.

  20. Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

    Science.gov (United States)

    Blanco, Eduardo; Galeano, Pablo; Palomino, Ana; Pavón, Francisco J; Rivera, Patricia; Serrano, Antonia; Alen, Francisco; Rubio, Leticia; Vargas, Antonio; Castilla-Ortega, Estela; Decara, Juan; Bilbao, Ainhoa; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2016-03-01

    In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate-related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE-PLD) and diacylglycerol lipase alpha (DAGLα). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE-PLD/fatty acid amide hydrolase and DAGLα/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could

  1. Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer\\'s disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.

  2. Nicotine disrupts safety learning by enhancing fear associated with a safety cue via the dorsal hippocampus.

    Science.gov (United States)

    Connor, David A; Kutlu, Munir G; Gould, Thomas J

    2017-07-01

    Learned safety, a learning process in which a cue becomes associated with the absence of threat, is disrupted in individuals with post-traumatic stress disorder (PTSD). A bi-directional relationship exists between smoking and PTSD and one potential explanation is that nicotine-associated changes in cognition facilitate PTSD emotional dysregulation by disrupting safety associations. Therefore, we investigated whether nicotine would disrupt learned safety by enhancing fear associated with a safety cue. In the present study, C57BL/6 mice were administered acute or chronic nicotine and trained over three days in a differential backward trace conditioning paradigm consisting of five trials of a forward conditioned stimulus (CS)+ (Light) co-terminating with a footshock unconditioned stimulus followed by a backward CS- (Tone) presented 20 s after cessation of the unconditioned stimulus. Summation testing found that acute nicotine disrupted learned safety, but chronic nicotine had no effect. Another group of animals administered acute nicotine showed fear when presented with the backward CS (Light) alone, indicating the formation of a maladaptive fear association with the backward CS. Finally, we investigated the brain regions involved by administering nicotine directly into the dorsal hippocampus, ventral hippocampus, and prelimbic cortex. Infusion of nicotine into the dorsal hippocampus disrupted safety learning.

  3. Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate.

    Science.gov (United States)

    Woolley, Daniel G; Mantini, Dante; Coxon, James P; D'Hooge, Rudi; Swinnen, Stephan P; Wenderoth, Nicole

    2015-04-01

    Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well-learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting-state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior-only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior-only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation-related processing. © 2014 Wiley Periodicals, Inc.

  4. Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Iidaka, Tetsuya

    2017-12-01

    Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points.

    Science.gov (United States)

    Pena, R R; Pereira-Caixeta, A R; Moraes, M F D; Pereira, G S

    2014-10-01

    To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  7. Genetic variations in two seahorse species (Hippocampus mohnikei and Hippocampus trimaculatus): evidence for middle Pleistocene population expansion.

    Science.gov (United States)

    Zhang, Yanhong; Pham, Nancy Kim; Zhang, Huixian; Lin, Junda; Lin, Qiang

    2014-01-01

    Population genetic of seahorses is confidently influenced by their species-specific ecological requirements and life-history traits. In the present study, partial sequences of mitochondrial cytochrome b (cytb) and control region (CR) were obtained from 50 Hippocampus mohnikei and 92 H. trimaculatus from four zoogeographical zones. A total of 780 base pairs of cytb gene were sequenced to characterize mitochondrial DNA (mtDNA) diversity. The mtDNA marker revealed high haplotype diversity, low nucleotide diversity, and a lack of population structure across both populations of H. mohnikei and H. trimaculatus. A neighbour-joining (NJ) tree of cytb gene sequences showed that H. mohnikei haplotypes formed one cluster. A maximum likelihood (ML) tree of cytb gene sequences showed that H. trimaculatus belonged to one lineage. The star-like pattern median-joining network of cytb and CR markers indicated a previous demographic expansion of H. mohnikei and H. trimaculatus. The cytb and CR data sets exhibited a unimodal mismatch distribution, which may have resulted from population expansion. Mismatch analysis suggested that the expansion was initiated about 276,000 years ago for H. mohnikei and about 230,000 years ago for H. trimaculatus during the middle Pleistocene period. This study indicates a possible signature of genetic variation and population expansion in two seahorses under complex marine environments.

  8. Genetic variations in two seahorse species (Hippocampus mohnikei and Hippocampus trimaculatus: evidence for middle Pleistocene population expansion.

    Directory of Open Access Journals (Sweden)

    Yanhong Zhang

    Full Text Available Population genetic of seahorses is confidently influenced by their species-specific ecological requirements and life-history traits. In the present study, partial sequences of mitochondrial cytochrome b (cytb and control region (CR were obtained from 50 Hippocampus mohnikei and 92 H. trimaculatus from four zoogeographical zones. A total of 780 base pairs of cytb gene were sequenced to characterize mitochondrial DNA (mtDNA diversity. The mtDNA marker revealed high haplotype diversity, low nucleotide diversity, and a lack of population structure across both populations of H. mohnikei and H. trimaculatus. A neighbour-joining (NJ tree of cytb gene sequences showed that H. mohnikei haplotypes formed one cluster. A maximum likelihood (ML tree of cytb gene sequences showed that H. trimaculatus belonged to one lineage. The star-like pattern median-joining network of cytb and CR markers indicated a previous demographic expansion of H. mohnikei and H. trimaculatus. The cytb and CR data sets exhibited a unimodal mismatch distribution, which may have resulted from population expansion. Mismatch analysis suggested that the expansion was initiated about 276,000 years ago for H. mohnikei and about 230,000 years ago for H. trimaculatus during the middle Pleistocene period. This study indicates a possible signature of genetic variation and population expansion in two seahorses under complex marine environments.

  9. Intracerebroventricular Injection of Lipopolysaccharide Increases Gene Expression of Connexin32 Gap Junction in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Mohammad Abbasian

    2013-11-01

    Full Text Available Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx. Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 – among Connexins– is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS on Cx32 gene and protein expressions in rat hippocampus is evaluated. Methods: LPS (2.5μg/rat was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Results: Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P<0.001. However, no significant change was observed in Cx32 protein level. Conclusion: LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

  10. The Association of PTSD Symptom Severity with Localized Hippocampus and Amygdala Abnormalities

    Science.gov (United States)

    Akiki, Teddy J.; Averill, Christopher L.; Wrocklage, Kristen M.; Schweinsburg, Brian; Scott, J. Cobb; Martini, Brenda; Averill, Lynnette A.; Southwick, Steven M.; Krystal, John H.; Abdallah, Chadi G.

    2017-01-01

    Background The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest. Methods In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69). Results Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas re-experiencing symptoms explain most of the variance in the amygdala abnormality. Conclusion The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed US Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder. PMID:28825050

  11. Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

    Science.gov (United States)

    Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.

    2013-01-01

    Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior based on changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining brain regions contributing to the encoding, maintenance and retrieval of overlapping identity information during working memory using a delayed match-to-sample (DMS) task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the non-overlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and non-overlapping condition at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the DMS task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory while the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. PMID:23640112

  12. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    Science.gov (United States)

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

  13. Glucose, relational memory, and the hippocampus.

    Science.gov (United States)

    Stollery, Brian; Christian, Leonie

    2015-06-01

    Many studies suggest that glucose can temporarily enhance hippocampal-dependent memories. As the hippocampus plays a key role in associative learning, we examined the influence of glucose on verbal paired associate memory. This study examines how glucose modifies performance on a relational memory task by examining its influence on learning, subsequent forgetting and relearning. A selective reminding procedure was used to show high and low imagability paired associates to 80 participants, who were seen twice. On the first session, they received 25 g glucose pre-learning, 25 g glucose post-learning or placebo. On the second session, 1 week later, they received 25 g glucose or placebo. Cued-recall was evaluated after each learning trial, 1 week later to assess forgetting and after an opportunity to relearn the material forgotten. Glucose did not influence paired associate acquisition. Those given glucose pre-learning tended to forget less material the following week, and independently, glucose at retrieval facilitated cued-recall. Both forms of facilitation were equally apparent on low and high imagability pairs. The benefit of glucose pre-learning was eliminated once the paired associates had been seen again, but the benefit of glucose at retrieval extended into the second relearning trial. The discussion considers the cognitive processes and hippocampal basis for paired associate learning and retention and the implications for glucose's mode of action. It is proposed that glucose during encoding serves to make the delayed memories initially more available, whereas its influence during delayed retrieval makes available memories temporarily more accessible.

  14. Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

    Science.gov (United States)

    Nair, Sunila G; Gudelsky, Gary A

    2004-09-15

    The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

  15. Absence of the neurogenesis-dependent nuclear receptor TLX induces inflammation in the hippocampus.

    Science.gov (United States)

    Kozareva, Danka A; Hueston, Cara M; Ó'Léime, Ciarán S; Crotty, Suzanne; Dockery, Peter; Cryan, John F; Nolan, Yvonne M

    2017-08-20

    The orphan nuclear receptor TLX (Nr2e1) is a key regulator of hippocampal neurogenesis. Impaired adult hippocampal neurogenesis has been reported in neurodegenerative and psychiatric conditions including dementia and stress-related depression. Neuroinflammation is also implicated in the neuropathology of these disorders, and has been shown to negatively affect hippocampal neurogenesis. To investigate a role for TLX in hippocampal neuroinflammation, we assessed microglial activation in the hippocampus of mice with a spontaneous deletion of TLX. Results from our study suggest that a lack of TLX is implicated in deregulation of microglial phenotype and that consequently, the survival and function of newborn cells in the hippocampus is impaired. TLX may be an important target in understanding inflammatory-associated impairments in neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The complete mitochondrial genome of the big-belly seahorse, Hippocampus abdominalis (Lesson 1827).

    Science.gov (United States)

    Wang, Lei; Chen, Zaizhong; Leng, Xiangjun; Gao, Jianzhong; Chen, Xiaowu; Li, Zhongpu; Sun, Peiying; Zhao, Yuming

    2016-11-01

    In this study, the complete mitogenome sequence of the big-belly seahorse, Hippocampus abdominalis (Lesson, 1827) (Syngnathiformes: Syngnathidae), has been sequenced by the next-generation sequencing method. The assembled mitogenome is 16 521 bp in length which includes 13 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs genes. The overall base composition of the seahorse is 31.1% for A, 23.6% for C, 16.0% for G, 29.3% for T and shows 87% identities similar to tiger tail seahorse, Hippocampus comes. The complete mitogenome of the big-belly seahorse provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for seahorse family.

  17. Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus

    International Nuclear Information System (INIS)

    Baranowska-Bosiacka, I.; Strużyńska, L.; Gutowska, I.; Machalińska, A.; Kolasa, A.; Kłos, P.; Czapski, G.A.; Kurzawski, M.; Prokopowicz, A.; Marchlewicz, M.

    2013-01-01

    Highlights: ► Pre- and neonatal Pb exposure decreased the number of hippocampal neurons. ► Lead caused ultrastructural alterations in CA1 region of hippocampus. ► Hippocampus is highly vulnerable to low level perinatal Pb exposure. ► Lead decreased BDNF level in the developing brain. ► Decreased Bax/Bcl2 ratio may protect hippocampus against Pb-induced apoptosis. -- Abstract: The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb) may intensify or inhibit apoptosis or necroptosis in the developing rat brain. Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring; the control group received distilled water. During the feeding of pups, mothers from the experimental group were still receiving PbAc. Pups were weaned at postnatal day 21 and the young rats of both groups then received only distilled water until postnatal day 28. This treatment protocol resulted in a concentration of Pb in rat offspring whole blood (Pb-B) below the threshold of 10 μg/dL, considered safe for humans.We studied Casp-3 activity and expression, AIF nuclear translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein expression as well as BDNF concentration in selected structures of the rat brain: forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic examinations showed alterations in hippocampal neurons.Our data shows that pre- and neonatal exposure of rats to Pb, leading to Pb-B below 10 μg/dL, can decrease the number of hippocampus neurons, occurring concomitantly with ultrastructural alterations in this region. We observed no morphological or molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF translocation to nucleus) in young brains, despite the reduced levels of BDNF. The potential protective factor against apoptosis was probably the decreased Bax/Bcl-2 ratio, which requires further investigation. Our

  18. A Mathematical Model for the Hippocampus: Towards the Understanding of Episodic Memory and Imagination

    Science.gov (United States)

    Tsuda, I.; Yamaguti, Y.; Kuroda, S.; Fukushima, Y.; Tsukada, M.

    How does the brain encode episode? Based on the fact that the hippocampus is responsible for the formation of episodic memory, we have proposed a mathematical model for the hippocampus. Because episodic memory includes a time series of events, an underlying dynamics for the formation of episodic memory is considered to employ an association of memories. David Marr correctly pointed out in his theory of archecortex for a simple memory that the hippocampal CA3 is responsible for the formation of associative memories. However, a conventional mathematical model of associative memory simply guarantees a single association of memory unless a rule for an order of successive association of memories is given. The recent clinical studies in Maguire's group for the patients with the hippocampal lesion show that the patients cannot make a new story, because of the lack of ability of imagining new things. Both episodic memory and imagining things include various common characteristics: imagery, the sense of now, retrieval of semantic information, and narrative structures. Taking into account these findings, we propose a mathematical model of the hippocampus in order to understand the common mechanism of episodic memory and imagination.

  19. Leukocyte telomere length and hippocampus volume: a meta-analysis [version 1; referees: 2 approved

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    Gustav Nilsonne

    2015-10-01

    Full Text Available Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.

  20. Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).

    Science.gov (United States)

    LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

    2012-03-01

    Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids.

  1. Deficient plasticity in the hippocampus and the spiral of addiction: focus on adult neurogenesis.

    Science.gov (United States)

    Canales, Juan J

    2013-01-01

    Addiction is a complex neuropsychiatric disorder which causes disruption at multiple levels, including cognitive, emotional, and behavioral domains. Traditional biological theories of addiction have focused on the mesolimbic dopamine pathway and the nucleus accumbens as anatomical substrates mediating addictive-like behaviors. More recently, we have begun to recognize the engagement and dynamic influence of a much broader circuitry which encompasses the frontal cortex, the amygdala, and the hippocampus. In particular, neurogenesis in the adult hippocampus has become a major focus of attention due to its ability to influence memory, motivation, and affect, all of which are disrupted in addiction. First, I summarize toxicological data that reveal strongly suppressive effects of drug exposure on adult hippocampal neurogenesis. Then, I discuss the impact of deficient neurogenesis on learning and memory function, stress responsiveness and affective behavior, as they relate to addiction. Finally, I examine recent behavioral observations that implicate neurogenesis in the adult hippocampus in the emergence and maintenance of addictive behavior. The evidence reviewed here suggests that deficient neurogenesis is associated with several components of the downward spiraling loop that characterizes addiction, including elevated sensitivity to drug-induced reward and reinforcement, enhanced neurohormonal responsiveness, emergence of a negative affective state, memory impairment, and inflexible behavior.

  2. Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

    Science.gov (United States)

    Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-01-01

    Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

  3. Regionalism, Regionalization and Regional Development

    Directory of Open Access Journals (Sweden)

    Liviu C. Andrei

    2016-03-01

    Full Text Available Sustained development is a concept associating other concepts, in its turn, in the EU practice, e.g. regionalism, regionalizing and afferent policies, here including structural policies. This below text, dedicated to integration concepts, will limit on the other hand to regionalizing, otherwise an aspect typical to Europe and to the EU. On the other hand, two aspects come up to strengthen this field of ideas, i.e. the region (al-regionalism-(regional development triplet has either its own history or precise individual outline of terms.

  4. Neurogenic effects of fingolimod in hippocampus, affecting fear memory.

    Directory of Open Access Journals (Sweden)

    Paschalis Efstathopoulos

    2014-05-01

    Full Text Available Fingolimod (FTY720; Gilenya™,Novartis Pharma AG is a recently developed Sphingosine-1-Phosphate (S1P analogue, orally administered as a new therapeutic agent in Multiple Sclerosis (MS (Brinkmann V. et al. 2010. S1P receptors (S1PRs are expressed in various sites in the CNS including the subventricular zone (Waeber C. et al. 1999; Choi J.W. et al. 2013 while endogenous S1P was shown to induce proliferation and morphological changes in embryonic hippocampal neural progenitors in culture (Harada J. et al. 2004. In this study we investigated the effects of fingolimod on adult rodent hippocampal neurogenesis and their possible functional role. To this aim, thymidine analogue BrdU was injected at the end or before a 2-week i.p. administration of a therapeutic dose of Fingolimod (0,3 mg/kg in young and old mice. Stereological counts of BrdU+ cells revealed significant increase in both proliferation, and survival of neural stem cells (NSC in the area of Dentate Gyrus (DG of the hippocampus, compared to control untreated animals of young but not old ages. In the case of survival assessment, most of the BrdU + cells were also positive for NeuN, suggesting an increase of newly formed neurons. The increase in proliferation rate of NSC was also confirmed by BrdU uptake in hippocampal NSC cultures in vitro, implying that the effects of fingolimod are cell autonomous. Immunohistochemical analysis showed that S1PR was not co-localized with GFAP+ cells in the Subgranular zone (SGZ of the DG, but was strongly co-localized with transcription factor MASH1 and weakly with DcX or PSA-NCAM positive neural progenitors. These findings suggest that expression of S1PR1 in the SGZ is restricted to transit amplifying neural progenitors and maintained also in the stage of neuroblast. In addition, the effects of Fingolimod in DG neurogenesis were positively correlated to enhanced fear memory and increased context discrimination, an established DG-dependent cognitive task

  5. Genetic evidence for monogamy in the dwarf seahorse, Hippocampus zosterae.

    Science.gov (United States)

    Rose, Emily; Small, Clayton M; Saucedo, Hector A; Harper, Cristin; Jones, Adam G

    2014-01-01

    Syngnathid fishes (pipefishes, seahorses, and seadragons) exhibit a wide array of mating systems ranging from monogamy with long-term pair bonds to more promiscuous mating systems, such as polyandry and polygynandry. Some seahorses, including the dwarf seahorse Hippocampus zosterae, have been found to be socially monogamous. Although several seahorse species have also been shown to be genetically monogamous, parentage analysis has not yet been applied to the dwarf seahorse. We developed 8 novel microsatellites for the dwarf seahorse to conduct genetic parentage analysis to confirm that this species is indeed monogamous. Using 4 selected loci and a total of 16 pregnant male seahorses, with 8 collected in Florida and 8 sampled in Texas, we genotyped all of the offspring within each male's brood to determine the maternal contributions to each brood. We found a maximum of 4 alleles per locus segregating within each pregnant male's brood, a pattern consistent with each brood having exactly 1 mother and 1 father. These results support previous laboratory-based behavioral studies and indicate that the dwarf seahorse, H. zosterae, is genetically monogamous. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Complete mitochondrial genome sequence of the Barbour's seahorse Hippocampus barbouri Jordan & Richardson, 1908 (Gasterosteiformes: Syngnathidae).

    Science.gov (United States)

    Wang, Bo; Zhang, Yanhong; Zhang, Huixian; Lin, Qiang

    2015-01-01

    The complete mitochondrial genome sequence of the Barbour's seahorse Hippocampus barbouri was first determined in this paper. The total length of H. barbouri mitogenome is 16,526 bp, which consists of 13 protein-coding genes, 22 tRNA and 2 rRNA genes and 1 control region. The features of the H. barbouri mitochondrial genome were similar to the typical vertebrates. The overall base composition of H. barbouri is 32.68% A, 29.75% T, 22.91% C and 14.66% G, with an AT content of 62.43%.

  7. Complete mitochondrial genome sequence of the lined seahorse Hippocampus erectus Perry, 1810 (Gasterosteiformes: Syngnathidae).

    Science.gov (United States)

    Zhang, Yanhong; Zhang, Huixian; Lin, Qiang; Huang, Liangmin

    2015-01-01

    The complete mitochondrial genome sequence of the lined seahorse Hippocampus erectus was first determined in this article. The total length of H. erectus mitogenome is 16,529 bp, which consists of 13 protein-coding genes, 22 tRNA and 2 rRNA genes and 1 control region. The features of the H. erectus mitochondrial genome were similar to the typical vertebrates. The overall base composition of H. erectus is 31.8% A, 28.6% T, 24.3% C and 15.3% G, with a slight A + T rich feature (60.4%).

  8. Complete mitochondrial genome of the pacific seahorse Hippocampus ingens Girard, 1858 (Gasterosteiformes: Syngnathidae).

    Science.gov (United States)

    Zhang, Huixian; Zhang, Yanhong; Lin, Qiang

    2015-01-01

    The complete mitochondrial genome sequence of the pacific seahorse Hippocampus ingens was determined using long polymerase chain reactions. The total length of H. ingens mitogenome is 16,526 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The gene order and composition of H. ingens were similar to those of most other vertebrates. The overall base composition of H. ingens is 32.6% A, 29.3% T, 23.5% G and 14.6% C, with a slight A+T rich feature (61.9%).

  9. Complete mitochondrial genome sequence of the longsnout seahorse Hippocampus reidi (Ginsburg, 1933; Gasterosteiformes: Syngnathidae).

    Science.gov (United States)

    Wang, Xin; Zhang, Yanhong; Zhang, Huixian; Meng, Tan; Lin, Qiang

    2016-01-01

    The complete mitochondrial genome sequence of the longsnout seahorse Hippocampus reidi was fisrt determined in this article. The total length of H. reidi mitogenome is 16,529 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The gene order and composition of H. reidi were similar to those of most other vertebrates. The overall base composition of H. reidi is 32.47% A, 29.41% T, 14.75% G and 23.37% C, with a slight A + T rich feature (61.88%).

  10. Intermittent hypercapnic hypoxia effects on the nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem.

    Science.gov (United States)

    Vivekanandarajah, Arunnjah; Aishah, Atqiya; Waters, Karen A; Machaalani, Rita

    2017-05-01

    This study investigated the effects of acute (1 day) vs repeated (4 days) exposure to intermittent hypercapnic hypoxia (IHH) on the immunohistochemical expression of α2, α3, α5, α7, α9 and β2 nicotinic acetylcholine receptor (nAChR) subunits in the developing piglet hippocampus and brainstem medulla, and how prior nicotine exposure alters the response to acute IHH. Five piglet groups included: 1day IHH (1D IHH, n=9), 4days IHH (4D IHH, n=8), controls exposed only to air cycles for 1day (1D Air, n=6) or 4days (4D Air, n=5), and pre-exposed to nicotine for 13days prior to 1day IHH (Nic+1D IHH, n=7). The exposure period alternated 6min of HH (8%O 2 , 7%CO 2 , balance N 2 ) and 6min of air over 48min, while controls were switched from air-to-air. Results showed that: 1. repeated IHH induces more changes in nAChR subunit expression than acute IHH in both the hippocampus and brainstem medulla, 2. In the hippocampus, α2 and β2 changed the most (increased) following IHH and the CA3, CA2 and DG were mostly affected. In the brainstem medulla, α2, α5, α9 and β2 were changed (decreased) in most nuclei with the hypoglossal and nucleus of the solitary tract being mostly affected. 3. Pre-exposure to nicotine enhanced the changes in the hippocampus but dampened those in the brainstem medulla. These findings indicate that the nAChRs (predominantly with the α2/β2 complex) are affected by IHH in critical hippocampal and brainstem nuclei during early brain development, and that pre-exposure to nicotine alters the pattern of susceptibility to IHH. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Cocaine withdrawal causes delayed dysregulation of stress genes in the hippocampus.

    Directory of Open Access Journals (Sweden)

    M Julia García-Fuster

    Full Text Available Relapse, even following an extended period of withdrawal, is a major challenge in substance abuse management. Delayed neurobiological effects of the drug during prolonged withdrawal likely contribute to sustained vulnerability to relapse. Stress is a major trigger of relapse, and the hippocampus regulates the magnitude and duration of stress responses. Recent work has implicated hippocampal plasticity in various aspects of substance abuse. We asked whether changes in stress regulatory mechanisms in the hippocampus may participate in the neuroadaptations that occur during prolonged withdrawal. We therefore examined changes in the rat stress system during the course of withdrawal from extended daily access (5-hours of cocaine self-administration, an animal model of addiction. Tissue was collected at 1, 14 and 28 days of withdrawal. Plasma corticosterone levels were determined and corticosteroid receptors (GR, MR, MR/GR mRNA ratios and expression of other stress-related molecules (HSP90AA1 and HSP90AB1 mRNA were measured in hippocampal subfields using in situ hybridization. Results showed a delayed emergence of dysregulation of stress genes in the posterior hippocampus following 28 days of cocaine withdrawal. This included increased GR mRNA in DG and CA3, increased MR and HSP90AA1 mRNA in DG, and decreased MR/GR mRNA ratio in DG and CA1. Corticosterone levels progressively decreased during the course of withdrawal, were normalized following 28 days of withdrawal, and were correlated negatively with GR and positively with MR/GR mRNA ratio in DG. These results suggest a role for the posterior hippocampus in the neuroadaptations that occur during prolonged withdrawal, and point to a signaling partner of GR, HSP90AA1, as a novel dysregulated target during cocaine withdrawal. These delayed neurobiological effects of extended cocaine exposure likely contribute to sustained vulnerability to relapse.

  12. Anatomic guidelines defined by reformatting images on MRI for volume measurement of amygdala and hippocampus

    International Nuclear Information System (INIS)

    Hoshida, Tohru; Sakaki, Toshisuke; Uematsu, Sumio.

    1995-01-01

    Twelve patients with intractable partial epilepsy underwent MR scans at the Epilepsy Center of the Johns Hopkins Hospital. There were five women and seven men, ranging in age from five to 51 years (mean age: 26 years). Coronal images were obtained using a 3-D SPGR. The coronal images were transferred to an Allegro 5.1 workstation, and reformatted along the cardinal axes (axial and sagittal) in multiple view points. The anterior end of the amygdala was measured at the level just posterior to the disappearance of the temporal stem. The semilunar gyrus of the amygdala was separated from the ambient gyrus by the semianular sulcus that forms the boundary between the amygdala and the entorhinal cortex. The delineation of the hippocampal formation included the subicular complex, hippocampal proper, dentate gyrus, alveus, and fimbria. The uncal cleft separated the uncus above from the parahippocampal gyrus below. The roof of this cleft was formed by the hippocampus and the dentate gyrus, and the floor, by the presubiculum and subiculum. Although using some guidelines, strictly separating the hippocampal head from the posterior part of the amygdala was not feasible as was previously reported, because of the isointensity on MRI between the cortex of the amygdala and the hippocampus. The most posterior portion of the hippocampus was measured at the level of the subsplenial gyri, just below the splenium of the corpus callosum, to measure the hippocampal volume in its near totality. Therefore, it is reliable, and clinically useful, to measure the combined total volume of the amygdala and the hippocampus when comparing results with those of other centers. (S.Y.)

  13. Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan); Department of Toxicology, Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510‐300 (China); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514‐8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514‐8507 (Japan); Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan); Ichihara, Gaku, E-mail: gak@med.nagoya-u.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466‐8550 (Japan)

    2012-08-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and humans. Previous proteomic analysis of rat hippocampus implicated alteration of protein expression in oxidative stress, suggesting that oxidative stress plays a role in 1-BP-induced neurotoxicity. To understand this role at the protein level, we exposed male F344 rats to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 week or 4 weeks by inhalation and quantitated changes in hippocampal protein carbonyl using a protein carbonyl assay, two-dimensional gel electrophoresis (2-DE), immunoblotting, and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). Hippocampal reactive oxygen species and protein carbonyl were significantly increased, demonstrating 1-BP-associated induction of oxidative stress and protein damage. MALDI-TOF-TOF/MS identified 10 individual proteins with increased carbonyl modification (p < 0.05; fold-change ≥ 1.5). The identified proteins were involved in diverse biological processes including glycolysis, ATP production, tyrosine catabolism, GTP binding, guanine degradation, and neuronal metabolism of dopamine. Hippocampal triosephosphate isomerase (TPI) activity was significantly reduced and negatively correlated with TPI carbonylation (p < 0.001; r = 0.83). Advanced glycation end-product (AGE) levels were significantly elevated both in the hippocampus and plasma, and hippocampal AGEs correlated negatively with TPI activity (p < 0.001; r = 0.71). In conclusion, 1-BP-induced neurotoxicity in the rat hippocampus seems to involve oxidative damage of cellular proteins, decreased TPI activity, and elevated AGEs. -- Highlights: ► 1-BP increases hippocampal ROS levels and hippocampal and plasma protein carbonyls. ► 1-BP increases TPI carbonylation and decreases TPI activity in the hippocampus. ► 1-BP increases hippocampal and plasma AGE levels.

  14. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    Science.gov (United States)

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  15. iTRAQ proteomic analysis of the hippocampus in a rat model of nicotine-induced conditioned place preference.

    Science.gov (United States)

    Zhu, Beibei; Li, Xiangyu; Chen, Huan; Wang, Hongjuan; Zhu, Xinchao; Hou, Hongwei; Hu, Qingyuan

    2017-05-13

    Repeated exposures to nicotine are known to result in persistent changes in proteins expression in addiction-related brain regions, such as the striatum, nucleus accumbens and prefrontal cortex, but the changes induced in the protein content of the hippocampus remain poorly studied. This study established a rat model of nicotine-induced conditioned place preference (CPP), and screened for proteins that were differentially expressed in the hippocampus of these rats using isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The nicotine-induced CPP was established by subcutaneously injecting rats with 0.2 mg/kg nicotine. Relative to the control (saline) group, the nicotine group showed 0.67- and 1.5-fold changes in 117 and 10 hippocampal proteins, respectively. These differentially expressed proteins are mainly involved in calcium-mediated signaling, neurotransmitter transport, GABAergic synapse function, long-term synaptic potentiation and nervous system development. Furthermore, RT-PCR was used to confirmed the results of the proteomic analysis. Our findings identify several proteins and cellular signaling pathways potentially involved in the molecular mechanisms in the hippocampus that underlie nicotine addiction. These results provide insights into the mechanisms of nicotine treatment in hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Involvement of dopamine receptors within the dorsal hippocampus in suppression of the formalin-induced orofacial pain.

    Science.gov (United States)

    Shamsizadeh, Ali; Pahlevani, Pouyan; Haghparast, Amir; Moslehi, Maryam; Zarepour, Leila; Haghparast, Abbas

    2013-12-01

    It is widely established that the dopaminergic system has profound effects on pain modulation in different regions of the brain including the hippocampus, the salient area for brain functions. The orofacial region is one of the most densely innervated (by the trigeminal nerves) areas of the body susceptible to acute and chronic pains. In this study, we tried to examine the effects of dopamine receptors located in the dorsal hippocampus (CA1) region upon the modulation of orofacial pain induced by the formalin test. To induce orofacial pain in male Wistar rats, 50μl of 1% formalin was subcutaneously injected into the upper lip. In control and experimental groups, two guide cannulae were stereotaxically implanted in the CA1, and SKF-38393 (0.25, 0.5, 1 and 2μg/0.5μl saline) as a D1-like receptor agonist, SCH-23390 (1μg/0.5μl saline) as a D1-like receptor antagonist, Quinpirole (0.5, 1, 2 and 4μg/0.5μl saline) as a D2-like receptor agonist and Sulpiride(3μg/0.5μl DMSO) as a D2-like receptor antagonist or vehicles were microinjected. For induction of orofacial pain, 50μl of 1% formalin was subcutaneously injected into the left side of the upper lip. Results indicated that SKF-38393 at the dose of 1 and 2μg significantly reduced pain during the first and second phases of observed pain while SCH-23390 reversed such analgesic effect. Moreover, there is a significant difference between groups in which animals received 2 and 4μg quinpirole or vehicle in the first phase (early phase) of pain. The three high doses of this compound (1, 2 and 4μg) appeared to have an analgesic effect during the second (late) phase. Furthermore, Sulpiride could potentially reverse the observed analgesic effects already induced by an agonist. Current findings suggest that the dorsal hippocampal dopamine receptors exert an analgesic effect during the orofacial pain test. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. GABAA receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex and superior temporal gyrus.

    Science.gov (United States)

    Kwakowsky, Andrea; Calvo-Flores Guzmán, Beatriz; Pandya, Madhavi; Turner, Clinton; Waldvogel, Henry J; Faull, Richard L

    2018-02-27

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA type A receptors (GABA A Rs) are severely affected in Alzheimer's disease (AD). However, the distribution and subunit composition of GABA A Rs in the AD brain are not well understood. This is the first comprehensive study to show brain region- and cell layer-specific alterations in the expression of the GABA A R subunits α1-3, α5, β1-3 and γ2 in the human AD hippocampus, entorhinal cortex and superior temporal gyrus (STG). In late-stage AD tissue samples using immunohistochemistry we found significant alteration of all investigated GABA A Rs subunits except for α3 and β1 that were well preserved. The most prominent changes include an increase in GABA A R α1 expression associated with AD in all layers of the CA3 region, in the stratum (str.) granulare and hilus of the dentate gyrus (DG). We found a significant increase in GABA A R α2 expression in the str. oriens of the CA1-3, str. radiatum of the CA2,3 and decrease in the str. pyramidale of the CA1 region in AD cases. In AD there was a significant increase in GABA A R α5 subunit expression in str. pyramidale, str. oriens of the CA1 region and decrease in the STG. We also found a significant decrease in the GABA A R β3 subunit immunoreactivity in the str. oriens of the CA2, str. granulare and str. moleculare of the DG. In conclusion, these findings indicate that the expression of the GABA A R subunits shows brain region- and layer-specific alterations in AD, and these changes could significantly influence and alter GABA A R function in the disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia

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    Seyedeh Farzaneh Moniri

    2018-01-01

    Full Text Available Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR, vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract. Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001. Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001. Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  19. Interplay of hippocampus and prefrontal cortex in memory

    Science.gov (United States)

    Preston, Alison R.; Eichenbaum, Howard

    2013-01-01

    Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

  20. Hippocampus is place of interaction between unconscious and conscious memories.

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    Marc Alain Züst

    Full Text Available Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked combinations of unfamiliar faces and written occupations ("actor" or "politician". At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious

  1. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    International Nuclear Information System (INIS)

    Oleskevich, S.; Descarries, L.; Lacaille, J.C.

    1989-01-01

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus

  2. 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

    2014-07-01

    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.

  3. Distribution Pattern of Seahorse species (Genus: Hippocampus in Tamilnadu and Kerala Coasts of India

    Directory of Open Access Journals (Sweden)

    Aaron Premnath LIPTON

    2013-02-01

    Full Text Available The survey along the Tamilnadu and Kerala coats of India reveled that six species of seahors (Hippocampus fuscus, H. kelloggi, H. kuda, H. histrix H. mohnikei and H. trimaculatus were distributed with different density. Out of the six species, H. fuscus, H. kuda and H. trimaculatus, were the commonly available species in all the observed areas. In Palk Bay, H. kuda was the dominant species constituting 49.10% of the total seahorses encountered. Hippocampus trimaculatus was the second dominant species which accounting 39.28%. The Gulf of Mannar region also most abounded with H. kuda (68.98% followed by H. trimaculatus (20.80%, H. fuscus (9.80%, H. kelloggi (2.23% and H. histrix (0.37%. In Kerala coast, H. trimaculatus was the dominant species (79.68% followed by H. kuda (9.89%, H. kelloggi (8.33% and H. fuscus (2.08%. To infer the variation of six seahorse species the morphometric and meristic characters were analysed. The important morphometric and meristic characters are trunk rings, tail rings, pectoral and dorsal fin rays, trunk length, tail length, coronet height, head length, snout length, snout depth and head depth. Variation in overall body shape, relative snout length, coronet height, number of tail ring was sufficient to separate the specimens to Hippocampus fuscus, H. kelloggi, H. kuda, H. histrix H. mohnikei and H.trimaculatus. The species density and diversity depends on the habitat and biogeography of those areas. Majority of seahorse fishing in Tamilnadu was by shrimp trawl, by-catch and very few target catch by divers also seen in some villages of Palk Bay and Gulf of Mannar region. The shrimp trawl by-catch only bringing more H. trimaculatus than the other species in Kerala coasts.

  4. 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

  5. Acute diffusion abnormalities in the hippocampus of children with new-onset seizures: the development of mesial temporal sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Farina, L. [Department of Neuroradiology, Istituto Nazionale Neurologico C. Besta, Milan (Italy); Department of Pediatrics, Division of Neurology, The Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Bergqvist, C.; Zimmerman, R.A.; Haselgrove, J.; Hunter, J.V.; Bilaniuk, L.T. [Department of Pediatrics, Division of Neurology, The Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Department of Radiology, The Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States)

    2004-04-01

    We studied the role of early diffusion-weighted imaging DWI in the investigation of children with new-onset prolonged seizures which eventually result in unilateral hippocampal sclerosis (HS). We carried out MRI on five children aged 17 months to 7 years including conventional and diffusion-weighted sequences. We calculated apparent diffusion coefficients (ADC) for the affected and the normal opposite hippocampus. Follow-up examinations were performed, including DWI and ADC measurements in four. We studied four children within 3 days of the onset of prolonged psychomotor seizures and showed increased signal on T2-weighted images, and DWI, indicating restricted diffusion, throughout the affected hippocampus. The ADC were reduced by a mean of 14.4% in the head and by 15% in the body of the hippocampus. In one child examined 15 days after the onset of seizures, the ADC were the same on both sides. All five patients showed hippocampal atrophy on follow-up 2-18 months later. In the four patients in whom ADC were obtained on follow-up, they were increased by 19% in the head and 17% in the body. DWI may represent a useful adjunct to conventional MRI for identifying acute injury to the hippocampus which results in sclerosis. (orig.)

  6. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

    International Nuclear Information System (INIS)

    Zhong, Yanjun; Dong, Guicheng; Luo, Haiguang; Cao, Jie; Wang, Chang; Wu, Jianyuan; Feng, Yu-Qi; Yue, Jiang

    2012-01-01

    Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

  7. Stimulus familiarity modulates functional connectivity of the perirhinal cortex and anterior hippocampus during visual discrimination of faces and objects

    Science.gov (United States)

    McLelland, Victoria C.; Chan, David; Ferber, Susanne; Barense, Morgan D.

    2014-01-01

    Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information. PMID:24624075

  8. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China); Fu, Qiang, E-mail: fuqiang@cpu.edu.cn [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China); Ma, Shiping, E-mail: spma@cpu.edu.cn [Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 639, Longmian Road, Nanjing 211198 (China); Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing 211198 (China)

    2015-07-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.

  9. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

    International Nuclear Information System (INIS)

    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin; Fu, Qiang; Ma, Shiping

    2015-01-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress

  10. Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

    Science.gov (United States)

    Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-01-01

    The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

  11. Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

    Science.gov (United States)

    Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

    2017-12-15

    Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Adult hippocampus derived soluble factors induce a neuronal-like phenotype in mesenchymal stem cells.

    Science.gov (United States)

    Rivera, Francisco J; Sierralta, Walter D; Minguell, Jose J; Aigner, Ludwig

    2006-10-02

    Bone marrow-derived mesenchymal stem cells (MSCs) are not restricted in their differentiation fate to cells of the mesenchymal lineage. They acquire a neural phenotype in vitro and in vivo after transplantation in the central nervous system. Here we investigated whether soluble factors derived from different brain regions are sufficient to induce a neuronal phenotype in MSCs. We incubated bone marrow-derived MSCs in conditioned medium (CM) derived from adult hippocampus (HCM), cortex (CoCM) or cerebellum (CeCM) and analyzed the cellular morphology and the expression of neuronal and glial markers. In contrast to muscle derived conditioned medium, which served as control, conditioned medium derived from the different brain regions induced a neuronal morphology and the expression of the neuronal markers GAP-43 and neurofilaments in MSCs. Hippocampus derived conditioned medium had the strongest activity. It was independent of NGF or BDNF; and it was restricted to the neuronal differentiation fate, since no induction of the astroglial marker GFAP was observed. The work indicates that soluble factors present in the brain are sufficient to induce a neuronal phenotype in MSCs.

  13. Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes

    Directory of Open Access Journals (Sweden)

    J.D. Ragland

    2017-01-01

    Conclusions: Results suggest a gradient of hippocampal dysfunction in which posterior hippocampus – which is necessary for processing fine-grained spatial relationships – is underactive, and anterior hippocampus – which may process context more globally - is overactive.

  14. Neurons of the dentate molecular layer in the rabbit hippocampus.

    Directory of Open Access Journals (Sweden)

    Francisco J Sancho-Bielsa

    Full Text Available The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals' life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections, eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population.

  15. Roles of the basolateral amygdala and hippocampus in social recognition

    NARCIS (Netherlands)

    Gispen, W.H.; Maaswinkel, H.; Baars, A.M.; Spruijt, B.M.

    1996-01-01

    Lesions of the amygdala or hippocampus have a large impact on social behavior of rats. In this study we investigated whether a social recognition test was also affected by those lesions. An NMDA-induced lesion of the basolateral amygdala did not impair the ability to distinguish a familiar from an

  16. Amygdala and hippocampus enlargement during adolescence in autism.

    NARCIS (Netherlands)

    Groen, W.B.; Teluij, M.; Buitelaar, J.K.; Tendolkar, I.

    2010-01-01

    OBJECTIVE: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal

  17. Stress Effects on the Hippocampus: A Critical Review

    Science.gov (United States)

    Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J.

    2015-01-01

    Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal…

  18. Incomplete inversion of the hippocampus - a common developmental anomaly

    Energy Technology Data Exchange (ETDEWEB)

    Bajic, Dragan; Wang, Chen; Raininko, Raili [Uppsala University Hospital, Department of Radiology, Uppsala (Sweden); Kumlien, Eva; Mattsson, Peter [Uppsala University Hospital, Department of Neurology, Uppsala (Sweden); Lundberg, Staffan; Eeg-Olofsson, Orvar [Uppsala University Hospital, Department of Child Neurology, Uppsala (Sweden)

    2008-01-15

    Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies. (orig.)

  19. Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

    Science.gov (United States)

    Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

    2017-08-01

    We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

  20. Amygdala and Hippocampus Enlargement during Adolescence in Autism

    Science.gov (United States)

    Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

    2010-01-01

    Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

  1. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  2. Intrauterine growth restriction affects the preterm infant's hippocampus.

    Science.gov (United States)

    Lodygensky, Gregory A; Seghier, Mohammed L; Warfield, Simon K; Tolsa, Cristina Borradori; Sizonenko, Stephane; Lazeyras, François; Hüppi, Petra S

    2008-04-01

    The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

  3. Comparison of neurodegeneration between right and left hippocampus area in rats

    Directory of Open Access Journals (Sweden)

    Arezo Nahavandi

    2015-02-01

    Conclusion: Our study showed different manifestations of depression after UCMS. It showed that UCMS could lead to mental depression. This study showed that the right hippocampus was more sensitive to stress than the left hippocampus. In fact, UCMS resulted in depression. The study showed that the right hippocampus was more sensitive to stress than the left hippocampus. Therefore, the main function of the right hemisphere, which is adaptation to the new environment, is disturbed more.

  4. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  5. Dorsal hippocampus is necessary for visual categorization in rats.

    Science.gov (United States)

    Kim, Jangjin; Castro, Leyre; Wasserman, Edward A; Freeman, John H

    2018-02-23

    The hippocampus may play a role in categorization because of the need to differentiate stimulus categories (pattern separation) and to recognize category membership of stimuli from partial information (pattern completion). We hypothesized that the hippocampus would be more crucial for categorization of low-density (few relevant features) stimuli-due to the higher demand on pattern separation and pattern completion-than for categorization of high-density (many relevant features) stimuli. Using a touchscreen apparatus, rats were trained to categorize multiple abstract stimuli into two different categories. Each stimulus was a pentagonal configuration of five visual features; some of the visual features were relevant for defining the category whereas others were irrelevant. Two groups of rats were trained with either a high (dense, n = 8) or low (sparse, n = 8) number of category-relevant features. Upon reaching criterion discrimination (≥75% correct, on 2 consecutive days), bilateral cannulas were implanted in the dorsal hippocampus. The rats were then given either vehicle or muscimol infusions into the hippocampus just prior to various testing sessions. They were tested with: the previously trained stimuli (trained), novel stimuli involving new irrelevant features (novel), stimuli involving relocated features (relocation), and a single relevant feature (singleton). In training, the dense group reached criterion faster than the sparse group, indicating that the sparse task was more difficult than the dense task. In testing, accuracy of both groups was equally high for trained and novel stimuli. However, both groups showed impaired accuracy in the relocation and singleton conditions, with a greater deficit in the sparse group. The testing data indicate that rats encode both the relevant features and the spatial locations of the features. Hippocampal inactivation impaired visual categorization regardless of the density of the category-relevant features for

  6. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes

    Directory of Open Access Journals (Sweden)

    Alicia Blaker-Lee

    2012-11-01

    Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs, intellectual disability disorder (IDD and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV. The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed ‘dosage sensors’, which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development – impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa and kinesin family member 22 (kif22 genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD.

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  7. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  8. Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK

    DEFF Research Database (Denmark)

    Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik

    2016-01-01

    , the presence of PER1 in hippocampal neurons is a prerequisite for the time-of-day-dependent phosphorylation of CREB, as it regulates the shuttling of pP90RSK into the nucleus. Representative immunofluorescence images show a temporal difference in phosphorylated cAMP response element-binding protein (p...... activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility......CREB; green color) levels in all regions of the dorsal hippocampus between a wild-type C3H mouse (WT; left) and a Period1-knockout (Per1−/−; right) mouse. Images were taken 2 h after lights on, thus, when fluctuating levels of pCREB peak in WT mouse hippocampus. Insets show a representative hippocampal neuron...

  9. Quantitative Measurements in the Human Hippocampus and Related Areas: Correspondence between Ex-Vivo MRI and Histological Preparations.

    Directory of Open Access Journals (Sweden)

    José Carlos Delgado-González

    Full Text Available The decrease of volume estimates in different structures of the medial temporal lobe related to memory correlate with the decline of cognitive functions in neurodegenerative diseases. This study presents data on the association between MRI quantitative parameters of medial temporal lobe structures and their quantitative estimate in microscopic examination. Twelve control cases had ex-vivo MRI, and thereafter, the temporal lobe of both hemispheres was sectioned from the pole as far as the level of the splenium of the corpus callosum. Nissl stain was used to establish anatomical boundaries between structures in the medial temporal lobe. The study included morphometrical and stereological estimates of the amygdaloid complex, hippocampus, and temporal horn of the lateral ventricle, as well as different regions of grey and white matter in the temporal lobe. Data showed a close association between morphometric MRI images values and those based on the histological determination of boundaries. Only values in perimeter and circularity of the piamater were different. This correspondence is also revealed by the stereological study, although irregular compartments resulted in a lesser agreement. Neither age ( 65 yr nor hemisphere had any effect. Our results indicate that ex-vivo MRI is highly associated with quantitative information gathered by histological examination, and these data could be used as structural MRI biomarker in neurodegenerative diseases.

  10. Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Miyuki eYoshiya

    2013-11-01

    Full Text Available Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes.We demonstrated rapid effects (~ 1 h of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500 and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR, abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100-1000 nM might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.

  11. Fourier transform infrared imaging showing reduced unsaturated lipid content in the hippocampus of a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Leskovjan, Andreana C; Kretlow, Ariane; Miller, Lisa M

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic =CH stretching mode at 3012 cm(-1). The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p avoiding progression of the disease.

  12. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole

    2017-01-01

    Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of...... in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease.......Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim...... that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia.NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead...

  13. Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

    Directory of Open Access Journals (Sweden)

    Haiyang Geng

    Full Text Available Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD. This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC. Fractional anisotropy (FA values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC region showing significant differences between the two groups was identified.Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

  14. Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats.

    Science.gov (United States)

    Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

    2007-08-01

    The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

  15. HDAC I inhibition in the dorsal and ventral hippocampus differentially modulates predator-odor fear learning and generalization.

    Science.gov (United States)

    Yuan, Robin K; Hebert, Jenna C; Thomas, Arthur S; Wann, Ellen G; Muzzio, Isabel A

    2015-01-01

    Although predator odors are ethologically relevant stimuli for rodents, the molecular pathways and contribution of some brain regions involved in predator odor conditioning remain elusive. Inhibition of histone deacetylases (HDACs) in the dorsal hippocampus has been shown to enhance shock-induced contextual fear learning, but it is unknown if HDACs have differential effects along the dorso-ventral hippocampal axis during predator odor fear learning. We injected MS-275, a class I HDAC inhibitor, bilaterally in the dorsal or ventral hippocampus of mice and found that it had no effects on innate anxiety in either region. We then assessed the effects of MS-275 at different stages of fear learning along the longitudinal hippocampal axis. Animals were injected with MS-275 or vehicle after context pre-exposure (pre-conditioning injections), when a representation of the context is first formed, or after exposure to coyote urine (post-conditioning injections), when the context becomes associated with predator odor. When MS-275 was administered after context pre-exposure, dorsally injected animals showed enhanced fear in the training context but were able to discriminate it from a neutral environment. Conversely, ventrally injected animals did not display enhanced learning in the training context but generalized the fear response to a neutral context. However, when MS-275 was administered after conditioning, there were no differences between the MS-275 and vehicle control groups in either the dorsal or ventral hippocampus. Surprisingly, all groups displayed generalization to a neutral context, suggesting that predator odor exposure followed by a mild stressor such as restraint leads to fear generalization. These results may elucidate distinct functions of the dorsal and ventral hippocampus in predator odor-induced fear conditioning as well as some of the molecular mechanisms underlying fear generalization.

  16. Selective WGA uptake in the hippocampus from the locus coeruleus of DBH-WGA transgenic mice

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    Susan G eWalling

    2012-05-01

    Full Text Available We generated transgenic mice in which a transsynaptic tracer, wheat germ agglutinin (WGA, was specifically expressed in the locus coeruleus neurons under the control of the dopamine-β-hydroxylase gene promoter. WGA protein was produced in more than 95% of the tyrosine hydroxylase-positive locus coeruleus neurons sampled. Transynaptic transfer of WGA was most evident in CA3 neurons of the hippocampus, but appeared absent in CA1 neurons. Faint but significant WGA immunoreactivity was observed surrounding the nuclei of dentate granule cells. Putative hilar mossy cells, identified by the presence of calretinin in the ventral hippocampus, appeared uniformly positive for transynaptically transferred WGA protein. GAD67-positive interneurons in the hilar and CA3 regions tended to be WGA-positive, although a subset of them did not show WGA co-localization. The same mixed WGA uptake profile was apparent when examining co-localization with parvalbumin. The selective uptake of WGA by dentate granule cells, mossy cells and CA3 pyramidal neurons is consistent with evidence for a large proportion of conventional synapses adjacent to locus coeruleus axonal varicosities in these regions. The lack of WGA uptake in the CA1 region and its relatively sparse innervation by dopamine-β-hydroxylase-positive fibers suggest that a majority of the tyrosine hydroxylase-positive classical synapses revealed by electron microscopy in that region may be producing dopamine. The overall pattern of WGA uptake in these transgenic mice suggests a selective role for the granule cell-mossy cell-CA3 network in processing novelty or the salient environmental contingency changes signaled by locus coeruleus activity.

  17. Modulation of the consolidation and reconsolidation of fear memory by three different serotonin receptors in hippocampus.

    Science.gov (United States)

    Schmidt, S D; Furini, C R G; Zinn, C G; Cavalcante, L E; Ferreira, F F; Behling, J A K; Myskiw, J C; Izquierdo, I

    2017-07-01

    The process of memory formation is complex and highly dynamic. During learning, the newly acquired information is found in a fragile and labile state. Through a process known as consolidation, which requires specific mechanisms such as protein synthesis, the memory trace is stored and stabilized. It is known that when a consolidated memory is recalled, it again becomes labile and sensitive to disruption. To be maintained, this memory must undergo an additional process of restabilization called reconsolidation, which requires another phase of protein synthesis. Memory consolidation has been studied for more than a century, while the molecular mechanisms underlying the memory reconsolidation are starting to be elucidated. For this, is essential compare the participation of important neurotransmitters and its receptors in both processes in brain regions that play a central role in the fear response learning. With focus on serotonin (5-HT), a well characterized neurotransmitter that has been strongly implicated in learning and memory, we investigated, in the CA1 region of the dorsal hippocampus, whether the latest discovered serotonergic receptors, 5-HT 5A , 5-HT 6 and 5-HT 7 , are involved in the consolidation and reconsolidation of contextual fear conditioning (CFC) memory. For this, male rats with cannulae implanted in the CA1 region received immediately after the training or reactivation session, or 3h post-reactivation of the CFC, infusions of agonists or antagonists of the 5-HT 5A , 5-HT 6 and 5-HT 7 receptors. After 24h, animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of the hippocampus the 5-HT 5A , 5-HT 6 and 5-HT 7 serotonin receptors participate in the reconsolidation of the CFC memory 3h post-reactivation. Additionally, the results suggest that the 5-HT 6 and 5-HT 7 receptors also participate in the consolidation of the CFC memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effect of Prolonged Simulated Microgravity on Metabolic Proteins in Rat Hippocampus: Steps toward Safe Space Travel.

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    Wang, Yun; Javed, Iqbal; Liu, Yahui; Lu, Song; Peng, Guang; Zhang, Yongqian; Qing, Hong; Deng, Yulin

    2016-01-04

    Mitochondria are not only the main source of energy in cells but also produce reactive oxygen species (ROS), which result in oxidative stress when in space. This oxidative stress is responsible for energy imbalances and cellular damage. In this study, a rat tail suspension model was used in individual experiments for 7 and 21 days to explore the effect of simulated microgravity (SM) on metabolic proteins in the hippocampus, a vital brain region involved in learning, memory, and navigation. A comparative (18)O-labeled quantitative proteomic strategy was used to observe the differential expression of metabolic proteins. Forty-two and sixty-seven mitochondrial metabolic proteins were differentially expressed after 21 and 7 days of SM, respectively. Mitochondrial Complex I, III, and IV, isocitrate dehydrogenase and malate dehydrogenase were down-regulated. Moreover, DJ-1 and peroxiredoxin 6, which defend against oxidative damage, were up-regulated in the hippocampus. Western blot analysis of proteins DJ-1 and COX 5A confirmed the mass spectrometry results. Despite these changes in mitochondrial protein expression, no obvious cell apoptosis was observed after 21 days of SM. The results of this study indicate that the oxidative stress induced by SM has profound effects on metabolic proteins.

  19. Characterizing context-dependent differential firing activity in the hippocampus and entorhinal cortex.

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    Prerau, Michael J; Lipton, Paul A; Eichenbaum, Howard B; Eden, Uri T

    2014-04-01

    The rat hippocampus and entorhinal cortex have been shown to possess neurons with place fields that modulate their firing properties under different behavioral contexts. Such context-dependent changes in neural activity are commonly studied through electrophysiological experiments in which a rat performs a continuous spatial alternation task on a T-maze. Previous research has analyzed context-based differential firing during this task by describing differences in the mean firing activity between left-turn and right-turn experimental trials. In this article, we develop qualitative and quantitative methods to characterize and compare changes in trial-to-trial firing rate variability for sets of experimental contexts. We apply these methods to cells in the CA1 region of hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC), characterizing the context-dependent differences in spiking activity during spatial alternation. We identify a subset of cells with context-dependent changes in firing rate variability. Additionally, we show that dcMEC populations encode turn direction uniformly throughout the T-maze stem, whereas CA1 populations encode context at major waypoints in the spatial trajectory. Our results suggest scenarios in which individual cells that sparsely provide information on turn direction might combine in the aggregate to produce a robust population encoding. Copyright © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2012-02-01

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

  1. Evidences of the role of the rodent hippocampus in the non-spatial recognition memory.

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    Yi, Jee Hyun; Park, Hye Jin; Kim, Byeong C; Kim, Dong Hyun; Ryu, Jong Hoon

    2016-01-15

    The hippocampus is a key region responsible for processing spatial information. However, the role of the hippocampus in non-spatial recognition memory is still controversial. In the present study, we performed hippocampal lesioning to address this controversy. The hippocampi of mice were disrupted with bilateral cytotoxic lesions, and standard object recognition (non-spatial) and object location recognition (spatial) were tested. In the habituation period, mice with hippocampal lesions needed a significantly longer time to fully habituate to the test box. Interestingly, after 4 days of habituation (insufficient habituation), the recognition index was similar in the sham and hippocampal lesion groups. However, exploration time was significantly shorter in mice with hippocampal lesions compared with that in control mice. Interestingly, if mice were subjected to a 10-days-long period of habituation (full habituation), the recognition index was significantly lower in mice with hippocampal lesions compared with that in control mice; however, total exploration time was similar in both groups. Furthermore, the object recognition test after full habituation occluded hippocampal long-term potentiation, a cellular model of memory. These results indicate that sufficient habituation is required to observe the effects of hippocampal lesions on object recognition memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus.

    Science.gov (United States)

    Besser, Limor; Chorin, Ehud; Sekler, Israel; Silverman, William F; Atkin, Stan; Russell, James T; Hershfinkel, Michal

    2009-03-04

    Zn(2+) is coreleased with glutamate from mossy fiber terminals and can influence synaptic function. Here, we demonstrate that synaptically released Zn(2+) activates a selective postsynaptic Zn(2+)-sensing receptor (ZnR) in the CA3 region of the hippocampus. ZnR activation induced intracellular release of Ca(2+), as well as phosphorylation of extracellular-regulated kinase and Ca(2+)/calmodulin kinase II. Blockade of synaptic transmission by tetrodotoxin or CdCl inhibited the ZnR-mediated Ca(2+) rises. The responses mediated by ZnR were largely attenuated by the extracellular Zn(2+) chelator, CaEDTA, and in slices from mice lacking vesicular Zn(2+), suggesting that synaptically released Zn(2+) triggers the metabotropic activity. Knockdown of the expression of the orphan G-protein-coupled receptor 39 (GPR39) attenuated ZnR activity in a neuronal cell line. Importantly, we observed widespread GPR39 labeling in CA3 neurons, suggesting a role for this receptor in mediating ZnR signaling in the hippocampus. Our results describe a unique role for synaptic Zn(2+) acting as the physiological ligand of a metabotropic receptor and provide a novel pathway by which synaptic Zn(2+) can regulate neuronal function.

  3. Enhanced expression of WD repeat-containing protein 35 (WDR35 stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation

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    Tsunekawa Koji

    2013-01-01

    Full Text Available Abstract Background Domoic acid (DA is an excitatory amino acid analogue of kainic acid (KA that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo. Results Our results showed that intraperitoneally administered DA was present in the brain and induced neurodegenerative changes including apoptosis in the CA1 region of the hippocampus. DA also increased the expression of WDR35 mRNA and protein in a dose- and time-dependent manner in the hippocampus. In experiments using glutamate receptor antagonists, the AMPA/KA receptor antagonist NBQX significantly attenuated the DA-induced increase in WDR35 protein expression, but the NMDA receptor antagonist MK-801 did not. In addition, the radical scavenger edaravone significantly attenuated the DA-induced increase in WDR35 protein expression. Furthermore, NBQX and edaravone significantly attenuated the DA-induced increase in p38 MAPK phosphorylation. Conclusion In summary, our results indicated that DA activated AMPA/KA receptors and induced ROS production and p38 MAPK phosphorylation, resulting in an increase in the expression of WDR35 in vivo.

  4. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

  5. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

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    Bruno P. Carreira

    2015-01-01

    Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

  6. MOLECULAR BASIS OF LEARNING IN THE HIPPOCAMPUS AND THE AMYGDALA

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    Łukasz BIJOCH

    2015-12-01

    Full Text Available The hippocampus and the amygdala are structures of mammalian brain both involved in memorizing. However, they are responsible for different types of memory: the hippocampus is involved in creating and storing declarative engrams and the amygdala is engaged in some of non-declarative learning. During memorization, changes of synapses appear and it is believed that they encode information. Long-Term Potentiation (LTP and Long-Term Depression (LTD are two processes which provide to these changes which are called synaptic plasticity. LTP strengthens connections between neurons and because of that it is traditionally linked with learning. LTD as an opposite state is usually treated as forgetting. However, there are some evidences that it is true only for few types of non-declarative engrams. More sophisticated learning (like declarative learning requires cooperation of these processes. Review is focused on functions and detailed signaling pathways of processes of synaptic plasticity.

  7. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

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    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

  8. Infusions of allopregnanolone into the hippocampus and amygdala, but not into the nucleus accumbens and medial prefrontal cortex, produce antidepressant effects on the learned helplessness rats.

    Science.gov (United States)

    Shirayama, Yukihiko; Muneoka, Katsumasa; Fukumoto, Makoto; Tadokoro, Shigenori; Fukami, Goro; Hashimoto, Kenji; Iyo, Masaomi

    2011-10-01

    Patients with depression showed a decrease in plasma and cerebrospinal fluid allopregnanolone (ALLO). But antidepressants increased the contents of ALLO in the rat brain. We examined the antidepressant-like effects of infusion of ALLO into the cerebral ventricle, hippocampus, amygdala, nucleus accumbens, or prefrontal cortex of learned helplessness (LH) rats (an animal model of depression). Of these regions, infusions of ALLO into the cerebral ventricle, the CA3 region of hippocampus, or the central region of amygdala exerted antidepressant-like effects. Infusion of ALLO into the hippocampal CA3 region or the central amygdala did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. It is well documented that ALLO exerts its effects through GABA receptors. Therefore, we examined the antagonistic effects of flumazenil (a GABA receptor antagonist) on the antidepressant-like effects of ALLO. Coinfusion of flumazenil with ALLO into the hippocampal CA3 region, but not into the central amygdala, blocked the antidepressant-like effects of ALLO. However, coinfusion of (+)MK801 (an NMDA receptor antagonist), but not cycloheximide (a protein synthesis inhibitor), blocked the antidepressant-like effects of ALLO in the central amygdala. These results suggest that ALLO exerts antidepressant-like effects in the CA3 region of hippocampus through the GABA system and in the central region of amygdala, dependently on the activation of the glutamatergic mechanisms. Copyright © 2010 Wiley-Liss, Inc.

  9. Age-dependent changes in autophosphorylation of alpha calcium/calmodulin dependent kinase II in hippocampus and amygdala after contextual fear conditioning.

    Science.gov (United States)

    Fang, Ton; Kasbi, Kamillia; Rothe, Stephanie; Aziz, Wajeeha; Giese, K Peter

    2017-09-01

    The hippocampus and amygdala are essential brain regions responsible for contextual fear conditioning (CFC). The autophosphorylation of alpha calcium-calmodulin kinase II (αCaMKII) at threonine-286 (T286) is a critical step implicated in long-term potentiation (LTP), learning and memory. However, the changes in αCaMKII levels with aging and training in associated brain regions are not fully understood. Here, we studied how aging and training affect the levels of phosphorylated (T286) and proportion of phosphorylated:total αCaMKII in the hippocampus and amygdala. Young and aged mice, naïve (untrained) and trained in CFC, were analysed by immunohistochemistry for the levels of total and phosphorylated αCaMKII in the hippocampus and amygdala. We found that two hours after CFC training, young mice exhibited a higher level of phosphorylated and increased ratio of phosphorylated:total αCaMKII in hippocampal CA3 stratum radiatum. Furthermore, aged untrained mice showed a higher ratio of phosphorylated:total αCaMKII in the CA3 region of the hippocampus when compared to the young untrained group. No effect of training or aging were seen in the central, lateral and basolateral amygdala regions, for both phosphorylated and ratio of phosphorylated:total αCaMKII. These results show that aging impairs the training-induced upregulation of autophosphorylated (T286) αCaMKII in the CA3 stratum radiatum of the hippocampus. This indicates that distinct age-related mechanisms underlie CFC that may rely more heavily on NMDA receptor-dependent plasticity in young age. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

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    Wittwer Matthias

    2006-06-01

    Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential

  11. Identification and characterization of PPAR? ligands in the hippocampus

    OpenAIRE

    Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K.; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J.; Pahan, Kalipada

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPAR?) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently, we have found that PPAR? is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here, three endogenous ligands of PPAR?, 3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide were discovered in mouse brain hippocampus. Mass spectrometric detect...

  12. Sleep in the human hippocampus: a stereo-EEG study.

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    Fabio Moroni

    Full Text Available BACKGROUND: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii a flattening of the time course of the very low frequencies (up to 1 Hz across sleep cycles, with relatively high levels of power even during REM sleep; iii a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. CONCLUSIONS/SIGNIFICANCE: Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory.

  13. Visual cortex plasticity evokes excitatory alterations in the hippocampus

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    Marian Tsanov

    2009-11-01

    Full Text Available The integration of episodic sequences in the hippocampus is believed to occur during theta rhythm episodes, when cortico-hippocampal dialog results in reconfiguration of neuronal assemblies. As the visual cortex (VC is a major source of sensory information to the hippocampus, information processing in the cortex may affect hippocampal network oscillations, facilitating the induction of synaptic modifications. We investigated to what degree the field activity in the primary VC, elicited by sensory or electrical stimulation, correlates with hippocampal oscillatory and synaptic responsiveness, in freely behaving adult rats. We found that the spectral power of theta rhythm (4-10Hz in the dentate gyrus (DG, increases in parallel with high-frequency oscillations in layer 2/3 of the VC and that this correlation depends on the degree of exploratory activity. When we mimic robust thalamocortical activity by theta-burst application to dorsal lateral geniculate nucleus, a hippocampal theta increase occurs, followed by a persistent potentiation of the DG granule field population spike. Furthermore, the potentiation of DG neuronal excitability tightly correlates with the concurrently occurring VC plasticity. The concurrent enhancement of VC and DG activity is also combined with a highly negative synchronization between hippocampal and cortical low frequency oscillations. Exploration of familiar environment decreases the degree of this synchrony. Our data propose that novel visual information can induce high-power fluctuations in intrinsic excitability for both VC and hippocampus, potent enough to induce experience-dependent modulation of cortico-hippocampal connections. This interaction may comprise one of the endogenous triggers for long-term synaptic plasticity in the hippocampus.

  14. Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale

    International Nuclear Information System (INIS)

    Altman, J.; Bayer, S.A.

    1990-01-01

    In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22

  15. Extracellular metabolites in the cortex and hippocampus of epileptic patients.

    Science.gov (United States)

    Cavus, Idil; Kasoff, Willard S; Cassaday, Michael P; Jacob, Ralph; Gueorguieva, Ralitza; Sherwin, Robert S; Krystal, John H; Spencer, Dennis D; Abi-Saab, Walid M

    2005-02-01

    Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites. The epileptogenic hippocampus had surprisingly high basal glutamate levels, low glutamine/glutamate ratio, high lactate levels, and indication for poor glucose utilization. The epileptogenic cortex had only marginally increased glutamate levels. We propose that interictal energetic deficiency in the epileptogenic hippocampus could contribute to impaired glutamate reuptake and glutamate-glutamine cycling, resulting in persistently increased extracellular glutamate, glial and neuronal toxicity, increased lactate production together with poor lactate and glucose utilization, and ultimately worsening energy metabolism. Our data suggest that a different neurometabolic process underlies the neocortical epilepsies.

  16. Characterization of NMDAR-independent learning in the hippocampus.

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    Kaycie Kuss Tayler

    2011-05-01

    Full Text Available It is currently thought that memory formation requires the activation of NMDA receptors (NMDARs in the hippocampus. However, recent studies indicate that these receptors are not necessary for all forms of learning. The current experiments examine this issue using context fear conditioning in mice. First, we show that context fear can be acquired without NMDAR activation in previously trained animals. Mice trained in one environment (context A are subsequently able to learn about a second environment (context B in the presence of NMDAR antagonists. Second, we demonstrate that NMDAR-independent learning requires the hippocampus and is dependent on protein synthesis. However, unlike NMDAR-dependent learning, it is not contingent on the expression of activity-regulated cytoskeleton-associated protein (Arc. Lastly, we present data that suggests NMDAR-independent learning is only observed when recently stimulated neurons are re-activated during conditioning. These data suggest that context fear conditioning modifies synaptic plasticity mechanisms in the hippocampus and allows subsequent learning to occur in the absence of NMDAR activation.

  17. The role of the hippocampus in memory and mental construction.

    Science.gov (United States)

    Sheldon, Signy; Levine, Brian

    2016-04-01

    Much has been learned about the processes that support the remembrance of past autobiographical episodes and their importance for a number of cognitive tasks. This work has focused on hippocampal contributions to constructing coherent mental representations of scenarios for these tasks, which has opened up new questions about the underlying hippocampal mechanisms. We propose a new framework to answer these questions, which incorporates task demands that prompt hippocampal contributions to mental construction, the online formation of such mental representations, and how these demands relate to the functional organization of the hippocampus. Synthesizing findings from autobiographical memory research, our framework suggests that the interaction of two task characteristics influences the recruitment of the hippocampus: (1) the degree of task open-endedness (quantified by the presence/absence of a retrieval framework) and (2) the degree to which the integration of perceptual details is required. These characteristics inform the relative weighting of anterior and posterior hippocampal involvement, following an organizational model in which the anterior and posterior hippocampus support constructions on the basis of conceptual and perceptual representations, respectively. The anticipated outcome of our framework is a refined understanding of hippocampal contributions to memory and to the host of related cognitive functions. © 2016 New York Academy of Sciences.

  18. Site fidelity and home range of the longsnout seahorse Hippocampus reidi (Teleostei: Syngnathidae) at the Varadero dock, northwest Cuba

    OpenAIRE

    de la Nuez Hernández, Daril; Pastor Gutiérrez, Lourdes; Pérez Angulo, Alejandro; Piloto Cubero, Yuliet; Corrada Wong, Raúl Igor

    2016-01-01

    Fish populations of the Syngnathidae family, including the charismatic seahorse, have significantly declined worldwide during the last decades. Up to now, these populations have been poorly researched in their habitat in Cuba. The objective of this study was to determinate site fidelity and home range of the longsnout seahorse (Hippocampus reidi Ginsburg, 1933), which has been poorly studied and has been classified as a Data Deficient (DD) species by the IUCN. Sampling was conducted between A...

  19. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

    Science.gov (United States)

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-01-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA (shRNA) to suppress expression of the enzyme CYP46A1. This protein hydroxylates cholesterol and so facilitates trans-membrane extrusion. A sh-RNA CYP46A1construction coupled to an adeno-associated virus (AAV5) was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the CA3a region. Cytoplasmic and membrane cholesterol increased, neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, inter-ictal EEG events occurred during exploration and non-REM sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low amplitude, high-frequency oscillations of peak power at ~300Hz and a range of 250-350 Hz. While episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behavior PMID:25847620

  20. Effect of complex aerobic physical exercise on PSD-95 in the hippocampus and on cognitive function in juvenile mice

    Science.gov (United States)

    Satriani, W. H.; Redjeki, S.; Kartinah, N. T.

    2017-08-01

    Increased neuroplasticity induced by complex aerobic physical exercise is associated with improved cognitive function in adult mice. Increased cognitive function is assumed to be based on increased synapse formation. One of the regions of the brain that is important in cognitive function is the hippocampus, which plays a role in memory formation. Post synaptic density-95 (PSD-95) is an adhesion protein of the post-synaptic density scaffolding that is essential to synaptic stabilization. As we age, the PSD-95 molecule matures the synapses needed for the formation of the basic circuitry of the nervous system in the brain. However, during the growth period, synapse elimination is higher than its formation. This study aims to determine whether complex aerobic exercise can improve cognitive function and PSD-95 levels in the hippocampus of juvenile mice during their growth stage. The mice performed complex aerobic exercise starting at five weeks of age and continuing for seven weeks with a gradual increase of 8 m/min. At eight weeks it was increased to 10 m/min. The exercise was done for five days of each week. The subjects of the study were tested for cognition one week before being sacrificed (at 12 weeks). The PSD-95 in the hippocampus was measured with ELISA. The results showed that there was a significant difference in cognitive function, where p cognitive ability in adulthood but does not increase the levels of PSD-95 in adults.

  1. Three-dimensional multivoxel spectroscopy of the healthy hippocampus-are the metabolic differences related to the location?

    Energy Technology Data Exchange (ETDEWEB)

    Ostojic, J., E-mail: sunns@eunet.y [Institute of Oncology Sremska Kamenica, Diagnostic Imaging Center, Institutski Put 4, 21204 Sremska Kamenica (Serbia); Kozic, D.; Konstantinovic, J. [Institute of Oncology Sremska Kamenica, Diagnostic Imaging Center, Institutski Put 4, 21204 Sremska Kamenica (Serbia); Covickovic-Sternic, N.; Mijajlovic, M. [Institute of Neurology, Clinical Center of Serbia, School of Medicine, University of Belgrade, Dr Subotica 6, 110000 Belgrade (Serbia); Koprivsek, K.; Semnic, R. [Institute of Oncology Sremska Kamenica, Diagnostic Imaging Center, Institutski Put 4, 21204 Sremska Kamenica (Serbia)

    2010-04-15

    Aim: The aim of this study was to determine the bilateral distribution of proton metabolites along the long axis of the hippocampus. Materials and methods: Forty-one healthy volunteers were examined using a 1.5 T magnetic resonance imaging system, using proton three-dimensional spectroscopic imaging (3D CSI) of the left and the right hippocampus separately. Three dominant signals were measured: choline (Cho), total creatine (tCr), and n-acetylaspartate (NAA) and expressed as ratios of Cho:tCr, NAA:tCr, NAA:Cho and NAA:(Cho+tCr). We compared the data from three hippocampal regions: head, body and tail. Results: Lower NAA:tCr ratios were found in head compared with the body (p<0.05) and in the head compared with the tail (p<0.05) bilaterally. Lower NAA:Cho and NAA:(Cho+tCr) ratios were found in the head compared with the body (p<0.05), in the body compared with the tail (p<0.05), and in the head compared with the tail (p<0.05) bilaterally. There was no statistically significant difference between the left and the right hippocampus. Conclusion: Ratios of NAA:tCr, NAA:Cho, and NAA:(Cho+tCr) in hippocampal tissue were significantly higher posteriorly than anteriorly. As the differences are present in healthy volunteers, the appearance in patients related to approximate voxel positioning within hippocampi may result in false-positive results.

  2. Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

    International Nuclear Information System (INIS)

    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J.

    1989-01-01

    In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 μM. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide

  3. Genetic evidence and new morphometric data as essential tools to identify the Patagonian seahorse Hippocampus patagonicus (Pisces, Syngnathidae).

    Science.gov (United States)

    González, R; Dinghi, P; Corio, C; Medina, A; Maggioni, M; Storero, L; Gosztonyi, A

    2014-02-01

    A genetic study to support morphometric analyses was used to improve the description and validate the Patagonian seahorse Hippocampus patagonicus (Syngnathidae) on the basis of a large number of specimens collected in the type locality (San Antonio Bay, Patagonia, Argentina). DNA sequence data (from the cytochrome b region of the mitochondrial genome) were used to differentiate this species from its relatives cited for the west Atlantic Ocean. Both phylogenetic and genetic distance analyses supported the hypothesis that H. patagonicus is a species clearly differentiated from others, in agreement with morphometric studies. Hippocampus patagonicus can be distinguished from Hippocampus erectus by the combination of the following morphometric characteristics: (1) in both sexes and all sizes of H. patagonicus, the snout length is always less than the postorbital length, whereas the snout length of H. erectus is not shorter than the postorbital length in the largest specimens; (2) in both sexes of H. patagonicus, the trunk length:total length (LTr :LT ) is lower than in H. erectus (in female H. patagonicus: 0·27-0·39, H. erectus: 0·36-0·40 and in male H. patagonicus: 0·24-0·34, H. erectus: 0·33-0·43) and (3) in both sexes, tail length:total length (LTa :LT ) in H. patagonicus is larger than in H. erectus (0·61-0·78 v. 0·54-0·64). © 2014 The Fisheries Society of the British Isles.

  4. Gender differences and lateralization in the distribution pattern of insulin-like growth factor-1 receptor in developing rat hippocampus: an immunohistochemical study.

    Science.gov (United States)

    Hami, Javad; Kheradmand, Hamed; Haghir, Hossein

    2014-03-01

    Numerous investigators have provided data supporting essential roles for insulin-like growth factor-I (IGF-I) in development of the brain. The aim of this study was to immunohistochemically determine the distinct regional distribution pattern of IGF-1 receptor (IGF-IR) expression in various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14), with comparison between male/female and right/left hippocampi. We found an overall significant increase in distribution of IGF-IR-positive (IGF-IR+) cells in CA1 from P0 until P14. Although, no marked changes in distribution of IGF-IR+ cells in areas CA2 and CA3 were observed; IGF-IR+ cells in DG decreased until P14. The smallest number of immunoreactive cells was present in CA2 and the highest number in DG at P0. Moreover, in CA1, CA3, and DG, the number of IGF-IR+ cells was markedly higher in both sides of the hippocampus in females. Our data also showed a higher mean number of IGF-IR+ cells in the left hippocampus of female at P7. By contrast, male pups showed a significantly higher number of IGF-IR+ cells in the DG of the right hippocampus. At P14, the mean number of immunoreactive cells in CA1, CA3, and DG areas found to be significantly increased in left side of hippocampus of males, compared to females. These results indicate the existence of a differential distribution pattern of IGF-IR between left-right and male-female hippocampi. Together with other mechanisms, these differences may underlie sexual dimorphism and left-right asymmetry in the hippocampus.

  5. Effects of HZE irradiation on chemical neurotransmission in rodent hippocampus

    Science.gov (United States)

    Machida, Mayumi

    Space radiation represents a significant risk to the CNS (central nervous system) during space missions. Most harmful are the HZE (high mass, highly charged (Z), high energy) particles, e.g. 56Fe, which possess high ionizing ability, dense energy deposition pattern, and high penetrance. Accumulating evidence suggests that radiation has significant impact on cognitive functions. In ground-base experiments, HZE radiation induces pronounced deficits in hippocampus dependent learning and memory in rodents. However, the mechanisms underlying these impairments are mostly unknown. Exposure to HZE radiation elevates the level of oxidation, resulting in cell loss, tissue damage and functional deficits through direct ionization and generation of reactive oxygen species (ROS). When hippocampal slices were exposed to ROS, neuronal excitability was reduced. My preliminary results showed enhanced radio-vulnerability of the hippocampus and reduction in basal and depolarization-evoked [3H]-norepinephrine release after HZE exposure. These results raised the possibility that HZE radiation deteriorates cognitive function through radiation-induced impairments in hippocampal chemical neurotransmission, the hypothesis of this dissertation. In Aim 1 I have focused on the effects of HZE radiation on release of major neurotransmitter systems in the hippocampus. I have further extended my research on the levels of receptors of these systems in Aim 2. In Aim 3, I have studied the level of oxidation in membranes of my samples. My research reveals that HZE radiation significantly reduces hyperosmotic sucrose evoked [3H]-glutamate and [14C]-GABA release both three and six months post irradiation. The same radiation regimen also significantly enhances oxidative stress as indicated by increased levels of lipid peroxidation in the hippocampus, suggesting that increased levels of lipid peroxidation may play a role in reduction of neurotransmitter release. HZE radiation also significantly reduces

  6. Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

    Science.gov (United States)

    Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

    2017-11-01

    Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

  7. Postnatal exposure to trichloroethylene alters glutathione redox homeostasis, methylation potential, and neurotrophin expression in the mouse hippocampus

    Science.gov (United States)

    Blossom, Sarah J.; Melnyk, Stepan; Cooney, Craig A.; Gilbert, Kathleen M.; James, S. Jill

    2012-01-01

    Previous studies have shown that continuous exposure throughout gestation until the juvenile period to environmentally-relevant doses of trichloroethylene (TCE) in the drinking water of MRL+/+ mice promoted adverse behavior associated with glutathione depletion in the cerebellum indicating increased sensitivity to oxidative stress. The purpose of this study was to extend our findings and further characterize the impact of TCE exposure on redox homeostasis and biomarkers of oxidative stress in the hippocampus, a brain region prone to oxidative stress. Instead of a continuous exposure, the mice were exposed to water only or two environmentally relevant doses of TCE in the drinking water postnatally from birth until 6 weeks of age. Biomarkers of plasma metabolites in the transsulfuration pathway and the transmethylation pathway of the methionine cycle were also examined. Gene expression of neurotrophins was examined to investigate a possible relationship between oxidative stress, redox imbalance and neurotrophic factor expression with TCE exposure. Our results show that hippocampi isolated from male mice exposed to TCE showed altered glutathione redox homeostasis indicating a more oxidized state. Also observed was a significant, dose dependent increase in glutathione precursors. Plasma from the TCE treated mice showed alterations in metabolites in the transsulfuration and transmethylation pathways indicating redox imbalance and altered methylation capacity. 3-Nitrotyrosine, a biomarker of protein oxidative stress, was also significantly higher in plasma and hippocampus of TCE-exposed mice compared to controls. In contrast, expression of key neurotrophic factors in the hippocampus (BDNF, NGF, and NT-3) was significantly reduced compared to controls. Our results demonstrate that low-level postnatal and early life TCE exposure modulates neurotrophin gene expression in the mouse hippocampus and may provide a mechanism for TCE-mediated neurotoxicity. PMID:22421312

  8. Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD)

    DEFF Research Database (Denmark)

    Medin, T; Rinholm, J E; Owe, S G

    2013-01-01

    A state of low dopaminergic activity has been implicated in attention-deficit/hyperactivity disorder (ADHD). The clinical symptoms of ADHD include inattention, impulsivity and hyperactivity, as well as impaired learning; dopaminergic modulation of the functions in the hippocampus is important......, indicating a reduced reservoir for insertion of receptors into the plasma membrane. DRs are important for long-term potentiation and long-term depression, hence the deficit may contribute to the learning difficulties in individuals with the diagnosis of ADHD....... to both learning and memory. To determine dopamine receptor (DR) density in a well-established animal model for ADHD, we quantified the dopamine D5 receptors in the hippocampus in the spontaneously hypertensive rat. We used immunofluorescence microscopy and immunogold electron microscopy to quantify...

  9. States of curiosity modulate hippocampus-dependent learning via the dopaminergic circuit.

    Science.gov (United States)

    Gruber, Matthias J; Gelman, Bernard D; Ranganath, Charan

    2014-10-22

    People find it easier to learn about topics that interest them, but little is known about the mechanisms by which intrinsic motivational states affect learning. We used functional magnetic resonance imaging to investigate how curiosity (intrinsic motivation to learn) influences memory. In both immediate and one-day-delayed memory tests, participants showed improved memory for information that they were curious about and for incidental material learned during states of high curiosity. Functional magnetic resonance imaging results revealed that activity in the midbrain and the nucleus accumbens was enhanced during states of high curiosity. Importantly, individual variability in curiosity-driven memory benefits for incidental material was supported by anticipatory activity in the midbrain and hippocampus and by functional connectivity between these regions. These findings suggest a link between the mechanisms supporting extrinsic reward motivation and intrinsic curiosity and highlight the importance of stimulating curiosity to create more effective learning experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. States of curiosity modulate hippocampus-dependent learning via the dopaminergic circuit

    Science.gov (United States)

    Gruber, Matthias J.; Gelman, Bernard D.; Ranganath, Charan

    2014-01-01

    Summary People find it easier to learn about topics that interest them, but little is known about the mechanisms by which intrinsic motivational states affect learning. We used functional magnetic resonance imaging to investigate how curiosity (intrinsic motivation to learn) influences memory. In both immediate and one-day delayed memory tests, participants showed improved memory for information that they were curious about, and also for incidental material learned during states of high curiosity. FMRI results revealed that activity in the midbrain and the nucleus accumbens was enhanced during states of high curiosity. Importantly, individual variability in curiosity-driven memory benefits for incidental material was supported by anticipatory activity in the midbrain and hippocampus and by functional connectivity between these regions. These findings suggest a link between the mechanisms supporting extrinsic reward motivation and intrinsic curiosity and highlight the importance of stimulating curiosity in order to create more effective learning experiences. PMID:25284006

  11. Complete mitochondrial genome sequence of the hedgehog seahorse Hippocampus spinosissimus Weber, 1933 (Gasterosteiformes:Syngnathidae).

    Science.gov (United States)

    Liu, Shuaishuai; Zhang, Yanhong; Wang, Changming; Lin, Qiang

    2016-07-01

    The complete mitochondrial genome sequence of the hedgehog seahorse Hippocampus spinosissimus was first determined in this article. The total length of H. spinosissimus mitogenome is 16 527 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The gene order and composition of H. spinosissimus were similar to those of most other vertebrates. The overall base composition of H. spinosissimus is 32.1% A, 30.3% T, 14.9% G and 22.7% C, with a slight A + T-rich feature (62.4%). Phylogenetic analyses based on complete mitochondrial genome sequence showed that H. spinosissimus has a close genetic relationship to H. ingens and H. kuda.

  12. Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

    Science.gov (United States)

    Disterhoft, J F; Segal, M

    1978-01-01

    Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

  13. A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer's Disease.

    Science.gov (United States)

    Liu, Chun-Han; Liu, Lian

    2017-05-08

    BACKGROUND Alzheimer's disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD. MATERIAL AND METHODS We proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected. RESULTS Pathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle. CONCLUSIONS We have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.

  14. A NEUROPHENOMENOLOGICAL MODEL FOR THE ROLE OF THE HIPPOCAMPUS IN TEMPORAL CONSCIOUSNES. EVIDENCE FROM CONFABULATION

    Directory of Open Access Journals (Sweden)

    Gianfranco eDalla Barba

    2015-08-01

    Full Text Available Confabulation, the production of statements or actions that are unintentionally incongruous to the subject’s history, background, present and future situation, is a rather infrequent disorder with different aetiologies and anatomical lesions. Although they may differ in many ways, confabulations show major similarities. Their content, with some minor exceptions, is plausible and therefore indistinguishable from true memories, unless one is familiar with the patient's history, background, present and future situation. They extend through the whole individuals’ temporality, including their past, present and future. Accordingly, we have proposed that rather than a mere memory disorder; confabulation reflects a distortion of Temporal Consciousness, i.e. a specific form of consciousness that allows individuals to locate objects and events according to their subjective temporality. Another feature that confabulators share is that, regardless of their lesion's location, they all have a relatively preserved hippocampus, at least unilaterally. In this article, we review data showing differences and similarities among forms of confabulation. We then describe a model showing that the hippocampus is crucial both for the normal functioning of Temporal Consciousness and as the generator of confabulations, and that different types of confabulation can be traced back to a distortion of Temporal Consciousness resulting from damage or

  15. Segmentation of the hippocampus by transferring algorithmic knowledge for large cohort processing.

    Science.gov (United States)

    Thyreau, Benjamin; Sato, Kazunori; Fukuda, Hiroshi; Taki, Yasuyuki

    2018-01-01

    The hippocampus is a particularly interesting target for neuroscience research studies due to its essential role within the human brain. In large human cohort studies, bilateral hippocampal structures are frequently identified and measured to gain insight into human behaviour or genomic variability in neuropsychiatric disorders of interest. Automatic segmentation is performed using various algorithms, with FreeSurfer being a popular option. In this manuscript, we present a method to segment the bilateral hippocampus using a deep-learned appearance model. Deep convolutional neural networks (ConvNets) have shown great success in recent years, due to their ability to learn meaningful features from a mass of training data. Our method relies on the following key novelties: (i) we use a wide and variable training set coming from multiple cohorts (ii) our training labels come in part from the output of the FreeSurfer algorithm, and (iii) we include synthetic data and use a powerful data augmentation scheme. Our method proves to be robust, and it has fast inference (deep neural-network methods can easily encode, and even improve, existing anatomical knowledge, even when this knowledge exists in algorithmic form. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex of rats in different phases of development.

    Science.gov (United States)

    Bruno, Alessandra Nejar; Da Silva, Rosane Souza; Bonan, Carla Denise; Battastini, Ana Maria Oliveira; Barreto-chaves, Maria Luiza M; Sarkis, João José Freitas

    2003-11-01

    Here we investigate the possible effects of the hyperthyroidism on the hydrolysis of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and blood serum of rats in different developmental phases. Manifestations of hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity and weight loss amongst others. The thyroid hormones modulate a number of physiological functions in central nervous system, including development, function, expression of adenosine A(1) receptors and transport of neuromodulator adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150- and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and adenosine production, interfering in neurotransmitter release, development and others physiological processes in different systems.

  17. Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

    Science.gov (United States)

    Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

    2015-10-01

    Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Encoding of emotion-paired spatial stimuli in the rodent hippocampus

    Directory of Open Access Journals (Sweden)

    Rebecca eNalloor

    2012-06-01

    Full Text Available Rats can acquire the cognitive component of CS-US associations between sensory and aversive stimuli without a functional basolateral amygdala. Thus, other brain regions should support such associations. Some septal/dorsal CA1 (dCA1 neurons respond to both spatial stimuli and footshock, suggesting that dCA1 could be one such region. We report that, in both dorsal and ventral hippocampus, different neuronal ensembles express immediate-early genes when a place is experienced alone vs. when it is associated with foot shock. We assessed changes in the size and overlap of hippocampal neuronal ensembles activated by two behavioral events using a cellular imaging method, Arc/Homer1a catFISH. The control group (A-A experienced the same place twice, while the experimental group (A-CFC received the same training plus two foot shocks during the second event. During fear conditioning, A-CFC, compared to A-A, rats had a smaller ensemble size in dCA3, dCA1 and vCA3, but not vCA1. Additionally, A-CFC rats had a lower overlap score in dCA1 and vCA3. Locomotion did not correlate with ensemble size. Importantly, foot shocks delivered in a training paradigm that prevents establishing shock-context associations, did not induce significant Arc expression, rejecting the possibility that the observed changes in ensemble size and composition simply reflect experiencing a foot shock. Combined with data that Arc is necessary for lasting synaptic plasticity and long-term memory, the data suggests that Arc/H1a+ hippocampal neuronal ensembles encode aspects of fear conditioning beyond space and time. Rats, like humans, may use the hippocampus to create integrated episodic-like memory during fear conditioning.

  19. Cranial irradiation alters dendritic spine density and morphology in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Ayanabha Chakraborti

    Full Text Available Therapeutic irradiation of the brain is a common treatment modality for brain tumors, but can lead to impairment of cognitive function. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and number are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. To gain some insight into the temporal and sub region specific cellular changes in the hippocampus following brain irradiation, we investigated the effects of 10 Gy cranial irradiation on dendritic spines in young adult mice. One week or 1 month post irradiation, changes in spine density and morphology in dentate gyrus (DG granule and CA1 pyramidal neurons were quantified using Golgi staining. Our results showed that in the DG, there were significant reductions in spine density at both 1 week (11.9% and 1 month (26.9% after irradiation. In contrast, in the basal dendrites of CA1 pyramidal neurons, irradiation resulted in a significant reduction (18.7% in spine density only at 1 week post irradiation. Analysis of spine morphology showed that irradiation led to significant decreases in the proportion of mushroom spines at both time points in the DG as well as CA1 basal dendrites. The proportions of stubby spines were significantly increased in both the areas at 1 month post irradiation. Irradiation did not alter spine density in the CA1 apical dendrites, but there were significant changes in the proportion of thin and mushroom spines at both time points post irradiation. Although the mechanisms involved are not clear, these findings are the first to show that brain irradiation of young adult animals leads to alterations in dendritic spine density and morphology in the hippocampus in a time dependent and region specific manner.

  20. Hippocampus and Basal Forebrain Volumetry for Dementia and Mild Cognitive Impairment Diagnosis: Could It Be Useful in Primary Care?

    Science.gov (United States)

    Teipel, Stefan J; Keller, Felix; Thyrian, Jochen R; Strohmaier, Urs; Altiner, Attila; Hoffmann, Wolfgang; Kilimann, Ingo

    2017-01-01

    Once a patient or a knowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations. To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as a proxy for cerebrovascular comorbidity on diagnostic accuracy. We determined hippocampus and BF volumes and white matter lesion load from MRI scans of 71 participants included in a primary care intervention trial (clinicaltrials.gov identifier: NCT01401582) and matched 71 participants stemming from a memory clinic. Samples included healthy controls and people with mild cognitive impairment (MCI), AD dementia, mixed dementia, and non-AD related dementias. Volumetric measures reached similar effect sizes and cross-validated levels of accuracy in the primary care and the memory clinic samples for the discrimination of AD and mixed dementia cases from healthy controls. In the primary care MCI cases, volumetric measures reached only random guessing levels of accuracy. White matter lesions had only a modest effect on effect size and diagnostic accuracy. Hippocampus and BF volumetry may usefully be employed for the identification of AD and mixed dementia, but the detection of MCI does not benefit from the use of these volumetric markers in a primary care setting.

  1. The Shift from a Response Strategy to Object-in-Place Strategy during Learning Is Accompanied by a Matching Shift in Neural Firing Correlates in the Hippocampus

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    Lee, Inah; Kim, Jangjin

    2010-01-01

    Hippocampal-dependent tasks often involve specific associations among stimuli (including egocentric information), and such tasks are therefore prone to interference from irrelevant task strategies before a correct strategy is found. Using an object-place paired-associate task, we investigated changes in neural firing patterns in the hippocampus in…

  2. Altered Neurochemical Ingredient of Hippocampus in Patients with Bipolar Depression

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    Murad Atmaca

    2012-01-01

    Full Text Available Background. In a number of investigations, hippocampal neurochemicals were evaluated in the patients with bipolar disorder who were on their first episode or euthymic periods. However, we did not meet any investigation in which only patients with bipolar depression were examined. As a consequence, the objective of the present study was to examine both sides of hippocampus of patients with bipolar disorder in depressive episode and healthy controls using 1H-MRS. Methods. Thirteen patients with DSM-IV bipolar I disorder, most recent episode depressed, were recruited from the Department of Psychiatry at Firat University School of Medicine. We also studied 13 healthy comparison subjects who were without any DSM-IV Axis I disorders recruited from the hospital staff. The patients and controls underwent proton magnetic resonance spectroscopy (1H-MRS of their hippocampus. NAA, CHO, and CRE values were measured. Results. No significant effect of diagnosis was observed for NAA/CRE ratio. For the NAA/CHO ratio, the ANCOVA with age, gender, and whole brain volume as covariates revealed that the patients with bipolar depression had significantly lower ratio compared to healthy control subjects for right and for left side. As for the CHO/CRE ratio, the difference was statistically significant for right side, with an effect diagnosis of F = 4.763, P = 0.038, and was very nearly significant for left side, with an effect diagnosis of F = 3.732, P = 0.064. Conclusions. We found that the patients with bipolar depression had lower NAA/CHO and higher CHO/CRE ratios compared to those of healthy control subjects. The findings of the present study also suggest that there may be a degenerative process concerning the hippocampus morphology in the patients with bipolar depression.

  3. Intracranial EEG correlates of implicit relational inference within the hippocampus.

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    Reber, T P; Do Lam, A T A; Axmacher, N; Elger, C E; Helmstaedter, C; Henke, K; Fell, J

    2016-01-01

    Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g., "winter-red," "red-cat") such that an indirect relation was established in following word pairs (e.g., "winter-cat"). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster "fit" judgments while the absence of indirect relations fostered "do not fit" judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1,500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future

  4. The hippocampus and exploration: dynamically evolving behavior and neural representations

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    Adam eJohnson

    2012-07-01

    Full Text Available We develop a normative statistical approach to exploratory behavior called information foraging. Information foraging highlights the specific processes that contribute to active, rather than passive, exploration and learning. We hypothesize that the hippocampus plays a critical role in active exploration through directed information foraging by supporting a set of processes that allow an individual to determine where to sample. By examining these processes, we show how information directed information foraging provides a formal theoretical explanation for the common hippocampal substrates of constructive memory, vicarious trial and error behavior, schema-based facilitation of memory performance, and memory consolidation.

  5. The hippocampus and exploration: dynamically evolving behavior and neural representations

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    Johnson, Adam; Varberg, Zachary; Benhardus, James; Maahs, Anthony; Schrater, Paul

    2012-01-01

    We develop a normative statistical approach to exploratory behavior called information foraging. Information foraging highlights the specific processes that contribute to active, rather than passive, exploration and learning. We hypothesize that the hippocampus plays a critical role in active exploration through directed information foraging by supporting a set of processes that allow an individual to determine where to sample. By examining these processes, we show how information directed information foraging provides a formal theoretical explanation for the common hippocampal substrates of constructive memory, vicarious trial and error behavior, schema-based facilitation of memory performance, and memory consolidation. PMID:22848196

  6. Muscarinic receptor compensation in hippocampus of alzheimer patients. [Autoradiography

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    Nordberg, A; Larsson, C; Adolfsson, R; Alafuzoff, I; Winblad, B [Uppsala Univ. (Sweden)

    1983-01-01

    The activity of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) (presynaptic marker) and number of muscarine-like receptor binding sites have been measured in the hippocampus from eight individuals with senile dementia of Alzheimer type (SDAT) and ten controls. A negative correlation (r=0.80; p<0.05) was found between the ChAT activity and the number of muscarine-like receptors in the SDAT group but not in the controls. The findings might indicate an ongoing compensatory receptor mechanism as a response to changes in presynaptic cholinergic activity.

  7. High glycogen levels in the hippocampus of patients with epilepsy

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Madsen, Flemming F; Secher, Niels H

    2006-01-01

    During intense cerebral activation approximately half of the glucose plus lactate taken up by the human brain is not oxidized and could replenish glycogen deposits, but the human brain glycogen concentration is unknown. In patients with temporal lobe epilepsy, undergoing curative surgery, brain......, glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained...

  8. Cholinergic markers in the cortex and hippocampus of some animal species and their correlation to Alzheimer's disease.

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    Orta-Salazar, E; Cuellar-Lemus, C A; Díaz-Cintra, S; Feria-Velasco, A I

    2014-10-01

    The cholinergic system includes neurons located in the basal forebrain and their long axons that reach the cerebral cortex and the hippocampus. This system modulates cognitive function. In Alzheimer's disease (AD) and ageing, cognitive impairment is associated with progressive damage to cholinergic fibres, which leads us to the cholinergic hypothesis for AD. The AD produces alterations in the expression and activity of acetyltransferase (ChAT) and acetyl cholinesterase (AChE), enzymes specifically related to cholinergic system function. Both proteins play a role in cholinergic transmission, which is altered in both the cerebral cortex and the hippocampus due to ageing and AD. Dementia disorders are associated with the severe destruction and disorganisation of the cholinergic projections extending to both structures. Specific markers, such as anti-ChAT and anti-AChE antibodies, have been used in light immunohistochemistry and electron microscopy assays to study this system in adult members of certain animal species. This paper reviews the main immunomorphological studies of the cerebral cortex and hippocampus in some animal species with particular emphasis on the cholinergic system and its relationship with the AD. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  9. Noninvasive focused ultrasound stimulation can modulate phase-amplitude coupling between neuronal oscillations in the rat hippocampus

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    Yi Yuan

    2016-07-01

    Full Text Available Noninvasive focused ultrasound stimulation (FUS can be used to modulate neural activity with high spatial resolution. Phase-amplitude coupling (PAC between neuronal oscillations is tightly associated with cognitive processes, including learning, attention and memory. In this study, we investigated the effect of FUS on PAC between neuronal oscillations and established the relationship between the PAC index and ultrasonic intensity. The rat hippocampus was stimulated using focused ultrasound at different spatial-average pulse-average ultrasonic intensities (3.9 W/cm2, 9.6 W/cm2, and 19.2 W/cm2. The local field potentials (LFPs in the rat hippocampus were recorded before and after FUS. Then, we analyzed PAC between neuronal oscillations using a PAC calculation algorithm. Our results showed that FUS significantly modulated PAC between the theta (4-8 Hz and gamma (30-80 Hz bands and between the alpha (9-13 Hz and ripple (81-200 Hz bands in the rat hippocampus, and PAC increased with incremental increases in ultrasonic intensity.

  10. Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

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    Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

    2016-01-01

    Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

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    Tsoory, M M; Vouimba, R M; Akirav, I; Kavushansky, A; Avital, A; Richter-Levin, G

    2008-01-01

    A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long

  12. Why looking at the whole hippocampus is not enough – a critical role for anteroposterior axis, subfield and activation analyses to enhance predictive value of hippocampal changes for Alzheimer’s disease diagnosis.

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    Aleksandra eMaruszak

    2014-03-01

    Full Text Available The hippocampus is one of the earliest affected brain regions in Alzheimer´s disease (AD and its dysfunction is believed to underlie the core feature of the disease- memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.

  13. Neural activity in the hippocampus during conflict resolution.

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    Sakimoto, Yuya; Okada, Kana; Hattori, Minoru; Takeda, Kozue; Sakata, Shogo

    2013-01-15

    This study examined configural association theory and conflict resolution models in relation to hippocampal neural activity during positive patterning tasks. According to configural association theory, the hippocampus is important for responses to compound stimuli in positive patterning tasks. In contrast, according to the conflict resolution model, the hippocampus is important for responses to single stimuli in positive patterning tasks. We hypothesized that if configural association theory is applicable, and not the conflict resolution model, the hippocampal theta power should be increased when compound stimuli are presented. If, on the other hand, the conflict resolution model is applicable, but not configural association theory, then the hippocampal theta power should be increased when single stimuli are presented. If both models are valid and applicable in the positive patterning task, we predict that the hippocampal theta power should be increased by presentation of both compound and single stimuli during the positive patterning task. To examine our hypotheses, we measured hippocampal theta power in rats during a positive patterning task. The results showed that hippocampal theta power increased during the presentation of a single stimulus, but did not increase during the presentation of a compound stimulus. This finding suggests that the conflict resolution model is more applicable than the configural association theory for describing neural activity during positive patterning tasks. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. THEORETICAL REVIEW The Hippocampus, Time, and Memory Across Scales

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    Howard, Marc W.; Eichenbaum, Howard

    2014-01-01

    A wealth of experimental studies with animals have offered insights about how neural networks within the hippocampus support the temporal organization of memories. These studies have revealed the existence of “time cells” that encode moments in time, much as the well-known “place cells” map locations in space. Another line of work inspired by human behavioral studies suggests that episodic memories are mediated by a state of temporal context that changes gradually over long time scales, up to at least a few thousand seconds. In this view, the “mental time travel” hypothesized to support the experience of episodic memory corresponds to a “jump back in time” in which a previous state of temporal context is recovered. We suggest that these 2 sets of findings could be different facets of a representation of temporal history that maintains a record at the last few thousand seconds of experience. The ability to represent long time scales comes at the cost of discarding precise information about when a stimulus was experienced—this uncertainty becomes greater for events further in the past. We review recent computational work that describes a mechanism that could construct such a scale-invariant representation. Taken as a whole, this suggests the hippocampus plays its role in multiple aspects of cognition by representing events embedded in a general spatiotemporal context. The representation of internal time can be useful across nonhippocampal memory systems. PMID:23915126

  15. The human hippocampus: cognitive maps or relational memory?

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    Kumaran, Dharshan; Maguire, Eleanor A

    2005-08-03

    The hippocampus is widely accepted to play a pivotal role in memory. Two influential theories offer competing accounts of its fundamental operating mechanism. The cognitive map theory posits a special role in mapping large-scale space, whereas the relational theory argues it supports amodal relational processing. Here, we pit the two theories against each other using a novel paradigm in which the relational processing involved in navigating in a city was matched with similar navigational and relational processing demands in a nonspatial (social) domain. During functional magnetic resonance imaging, participants determined the optimal route either between friends' homes or between the friends themselves using social connections. Separate brain networks were engaged preferentially during the two tasks, with hippocampal activation driven only by spatial relational processing. We conclude that the human hippocampus appears to have a bias toward the processing of spatial relationships, in accordance with the cognitive map theory. Our results both advance our understanding of the nature of the hippocampal contribution to memory and provide insights into how social networks are instantiated at the neural level.

  16. Alzheimer's disease and magnetic resonance spectroscopy of the hippocampus

    International Nuclear Information System (INIS)

    Engelhardt, Eliasz; Moreira, Denise M.; Laks, Jerson; Marinho, Valeska M.; Rozenthal, Marcia; Oliveira Junior, Amarino C.

    2001-01-01

    Objective: acquisition of data of magnetic resonance metabolite spectrum of the hippocampal formation (hippocampus-hc) in the elderly, normal and with Alzheimer's disease (AD). Method: Subjects matched for age: a. normal sample (n=20), CDR=0, and b. AD sample (n=40), CDR 1 and 2. Technique: Signa Horizon LX-GE, 1.5T, 1 H-MRS with automated software PROBE/SV, VOI: hc (right and left); single voxel (2x2x2cm); TR 1500ms/TE 50ms; PRESS; metabolites: N-acetylaspartate (Naa), choline (Cho), creatine (Cr), myo-inositol (mI). Results: The present data relate to the ratios of Naa, Cho and mI, with Cr taken as reference, and the mI/Naa ratio. The study showed reduction of Naa, increase of mI and of the mI/Naa ratio, and not consistent results for Cho. The results of the whole sample of AD patients compared to the pooled normal mean ± sd were significant for Naa, mI and mI/Naa (p<0.01). Accuracy in relation to the individual values of both samples showed satisfactory levels of sensitivity, specificity and positive predictive value. Conclusion: The present results can be used as a helpful tool to detect pathologic changes of the hippocampus in AD, and allowing greater accuracy and an earlier diagnosis of this disease. (author)

  17. The hippocampus facilitates integration within a symbolic field.

    Science.gov (United States)

    Cornelius, John Thor

    2017-10-01

    This paper attempts to elaborate a fundamental brain mechanism involved in the creation and maintenance of symbolic fields of thought. It will integrate theories of psychic spaces as explored by Donald Winnicott and Wilfred Bion with the neuroscientific examinations of those with bilateral hippocampal injury to show how evidence from both disciplines sheds important light on this aspect of mind. Possibly originating as a way of maintaining an oriented, first person psychic map, this capacity allows individuals a dynamic narrative access to a realm of layered elements and their connections. If the proposed hypothesis is correct, the hippocampus facilitates the integration of this symbolic field of mind, where narrative forms of thinking, creativity, memory, and dreaming are intertwined. Without the hippocampus, there is an inability to engage many typical forms of thought itself. Also, noting the ways these individuals are not impaired supports theories about other faculties of mind, providing insight into their possible roles within human thought. The evidence of different systems working in conjunction with the symbolic field provides tantalizing clues about these fundamental mechanisms of brain and mind that are normally seamlessly integrated, and hints at future areas of clinical and laboratory research, both within neuroscience and psychoanalysis. © 2017 The Authors. The International Journal of Psychoanalysis published by John Wiley & Sons Ltd on behalf of Institute of Psychoanalysis.

  18. Reliable activation of immature neurons in the adult hippocampus.

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    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  19. Regional hippocampal volumes and development predict learning and memory.

    Science.gov (United States)

    Tamnes, Christian K; Walhovd, Kristine B; Engvig, Andreas; Grydeland, Håkon; Krogsrud, Stine K; Østby, Ylva; Holland, Dominic; Dale, Anders M; Fjell, Anders M

    2014-01-01

    The hippocampus is an anatomically and functionally heterogeneous structure, but longitudinal studies of its regional development are scarce and it is not known whether protracted maturation of the hippocampus in adolescence is related to memory development. First, we investigated hippocampal subfield development using 170 longitudinally acquired brain magnetic resonance imaging scans from 85 participants aged 8-21 years. Hippocampal subfield volumes were estimated by the use of automated segmentation of 7 subfields, including the cornu ammonis (CA) sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change was quantified using a nonlinear registration procedure. Second, associations between subfield volumes and change and verbal learning/memory across multiple retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized that short and intermediate memory would be more closely related to CA2-3/CA4-DG and extended, remote memory to CA1. Change rates were significantly different across hippocampal subfields, but nearly all subfields showed significant volume decreases over time throughout adolescence. Several subfield volumes were larger in the right hemisphere and in males, while for change rates there were no hemisphere or sex differences. Partly in support of the hypotheses, greater volume of CA1 and CA2-3 was related to recall and retention after an extended delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning. This suggests continued regional development of the hippocampus across adolescence and that volume and volume change in specific subfields differentially predict verbal learning and memory over different retention intervals, but future high-resolution studies are called for. © 2014 S. Karger AG, Basel.

  20. Angiotensin IV possibly acts through PKMzeta in the hippocampus to regulate cognitive memory in rats.

    Science.gov (United States)

    Chow, Lok-Hi; Tao, Pao-Luh; Chen, Yuan-Hao; Lin, Yu-Hui; Huang, Eagle Yi-Kung

    2015-10-01

    Ang IV is an endogenous peptide generated from the degradation of angiotensin II. Ang IV was found to enhance learning and memory in CNS. PKMzeta was identified to be a fragment of PKCzeta (protein kinase Czeta). Its continuous activation was demonstrated to be correlated with the formation of memory in the hippocampus. Therefore, we investigated whether PKMzeta participates in the effects of Ang IV on memory. We first examined the effect of Ang IV on non-spatial memory/cognition in modified object recognition test in rats. Our data showed that Ang IV could increase the exploration time on novel object. The co-administration of ZIP (PKMzeta inhibitor) with Ang IV significantly blocked the effect by Ang IV. The effects of Ang IV on hippocampal LTP at the CA1 region were also evaluated. Ang IV significantly increased the amplitude and slope of the EPSPs, which was consistent with other reports. Surprisingly, instead of potentiating LTP, Ang IV caused a failed maintenance of LTP. Moreover, there was no quantitative change in PKMzeta induced by Ang IV and/or ZIP after behavioral experiments. Taken together, our data re-confirmed the finding of the positive effect of Ang IV to enhance memory/cognition. The increased strength of EPSPs with Ang IV could also have certain functional relevance. Since the behavioral results suggested the involvement of PKMzeta, we hypothesized that the enhancement of memory/cognition by Ang IV may rely on an increase in PKMzeta activity. Overall, the present study provided important advances in our understanding of the action of Ang IV in the hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The hippocampus in patients treated with electroconvulsive therapy: a proton magnetic resonance spectroscopic imaging study.

    Science.gov (United States)

    Ende, G; Braus, D F; Walter, S; Weber-Fahr, W; Henn, F A

    2000-10-01

    We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT-induced memory deterioration was associated with neuronal loss in the hippocampus, the N-acetylaspartate signal would decrease after ECT and any increased membrane turnover would result in an increase in the signal from choline-containing compounds. Seventeen patients received complete courses of ECT, during which repeated proton magnetic resonance spectroscopic imaging studies of the hippocampal region were performed. Individual changes during the course of ECT were compared with values obtained in 24 healthy control subjects and 6 patients remitted from major depression without ECT. No changes in the hippocampal N-acetylaspartate signals were detected after ECT. A significant mean increase of 16% of the signal from choline-containing compounds after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT application (14 of 17 patients), the increase in the choline-containing compound signal was observed bilaterally. Lactate or elevated lipid signals were not detected. All patients showed clinical amelioration of depression after ECT. Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal. Compared with an age-matched control group, the choline-containing compounds signal in patients with a major depressive episode was significantly lower than normal, before ECT and normalized during ECT.

  2. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Abdul-Rahman Omar

    2012-02-01

    Full Text Available Abstract Background There has been an increasing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Results Following pathway analysis and validation of gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1, CD47 (Cluster of Differentiation 47 and the RET (Rearranged During Transfection protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipid metabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus striatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. Conclusions According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes.

  3. Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus.

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2015-12-01

    Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

  4. Effects of hypergravic fields on serotonergic neuromodulation in the rat hippocampus.

    Science.gov (United States)

    Horrigan, D J; Fuller, C A; Horowitz, J M

    1997-10-01

    The effects of 7 day exposure to 2G fields on serotonergic modulation at two synapses on a hippocampal pathway were examined by recording dentate gyrus and CA1 pyramidal cell layer electrical activity. Serotonin decreased the amplitude of the population spike (synchronous action potentials in hundreds of neurons) in both the dentate gyrus and CA1 regions of rats exposed to 2G fields for 7 days. The inhibition, averaging 26 +/- 4% (mean +/- SEM) in the dentate gyrus and 80 +/- 5% in the CA1 region, was not significantly different from inhibitory responses observed in 1G controls. The 5-HT1A agonist 8-OH-DPAT mimicked this inhibition in the dentate and CA1 regions of 1G rats. 8-OH-DPAT responses were not affected by exposure to 2G fields. We conclude that the hippocampus contains surplus 5-HT receptors so that decreases in receptor density reported in receptor binding studies do not result in a decrease in modulatory capability. A model to account for the physiological pathway that relates gravitational field strength to 5-HT receptor density without changing the effectiveness of 5-HT neuromodulation is discussed.

  5. Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

    Science.gov (United States)

    Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

    2018-02-01

    The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

  6. Fourier Transform Infrared Imaging Shows Reduced Unsaturated Lipid Content in the Hippocampus of a Mouse Model of Alzheimer’s Disease

    OpenAIRE

    Leskovjan, Andreana C.; Kretlow, Ariane; Miller, Lisa M.

    2010-01-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer’s disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier Transform Infrared Imaging ...

  7. Population characteristics, space use and habitat associations of the seahorse Hippocampus reidi (Teleostei: Syngnathidae

    Directory of Open Access Journals (Sweden)

    Ierecê Lucena Rosa

    Full Text Available This paper provides a case study of a threatened seahorse species, Hippocampus reidi, highlighting the importance of using ecological information to assist conservation and management initiatives. Underwater visual sighting data (50 x 2m transect gathered along the NE, SE and S portions of the Brazilian coast revealed an unequal distribution across localities, perhaps related to harvesting pressure, and a mean density of 0.026 ind.m-2. Our findings suggest some restricted spatial use by H. reidi, which was consistent with its estimated home range, and with re-sighting of specimens. Reproduction was recorded year-round, however productive peaks may exist. Components of habitat structure mostly used as anchoring points were mangrove plants, macroalgae, cnidarians, seagrass, sponges, and bryozoans. Conservation recommendations include: further characterization and mapping of habitats; assessment of availability and condition of microhabitats in selected areas, and studies on dispersal routes during initial life stages.

  8. A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

    Science.gov (United States)

    Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

    1994-02-28

    Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

  9. First feeding regimes for long-snout seahorse Hippocampus reidi larvae.

    Science.gov (United States)

    Garcia-Manchón, J; Socorro-Cruz, J; Segade Botella, A; Otero-Ferrer, F; Mesa, A; Molina Domínguez, L

    2013-01-01

    Seahorses are endangered species included in Appendix II of CITES from 2002 due to the progressive regression of wild populations. This study focused in Hippocampus reidi, one of the species with highest interest in trade, showing an increasing demand in the last decades. This study was conducted during 28 days to compare the effects of different time enrichment (0, 24, and 48h) for Artemia using a commercial product (Easy-Selco DHA INVE Aquaculture, Dendermonde, Belgium). Results showed no significant differences in growth between treatments until 21DAB, after which animals fed for 48h one enriched Artemia showed significantly better growth. Cumulative average survival during the first 14DAB was significantly higher in Oh treatment, while from 15DAB to the end of the experiment, no significantly differences were observed.

  10. Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

    Science.gov (United States)

    Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

    2012-03-01

    Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

  11. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    Science.gov (United States)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  12. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice

    Directory of Open Access Journals (Sweden)

    M Zamani

    2013-01-01

    Full Text Available Introduction: Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Oxidative Stress is considered to be involved in a number of human diseases including ischemia. Preliminary studies confirmed reduction of cell death in brain following treatment with antioxidants. Aim: According to this finding, we study the relationship between consumption of olive oil on cell death and memory disorder in brain ischemia. We studied the protective effect of olive oil against ischemia-reperfusion. Material and Methods: Experimental design includes three groups: Intact (n = 8, ischemic control (n = 8 and treatment groups with olive oil (n = 8. The mice treated with olive oil as pre-treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction of inflammation [a week after ischemia], the mice post-treated with olive oil. Nissl staining applied for counting necrotic cells in hippocampus CA1. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply y-maze and shuttle box tests and for detection the rate of apoptotic and treated cell, we used western blotting test for bax and bcl2 proteins. Results: High rate of apoptosis was seen in ischemic group that significantly associated with short-term memory loss. Cell death was significantly lower when mice treated with olive oil. The memory test results were adjusted with cell death results and bax and bcl2 expression in all groups′ comparison. Ischemia for 15 min induced cell death in hippocampus with more potent effect on CA1. Conclusion: Olive oil intake significantly reduced cell death and decreased memory loss.

  13. Impaired mitochondrial respiration and protein nitration in the rat hippocampus after acute inhalation of combustion smoke

    International Nuclear Information System (INIS)

    Lee, Heung M.; Reed, Jason; Greeley, George H.; Englander, Ella W.

    2009-01-01

    Survivors of massive inhalation of combustion smoke endure critical injuries, including lasting neurological complications. We have previously reported that acute inhalation of combustion smoke disrupts the nitric oxide homeostasis in the rat brain. In this study, we extend our findings and report that a 30-minute exposure of awake rats to ambient wood combustion smoke induces protein nitration in the rat hippocampus and that mitochondrial proteins are a sensitive nitration target in this setting. Mitochondria are central to energy metabolism and cellular signaling and are critical to proper cell function. Here, analyses of the mitochondrial proteome showed elevated protein nitration in the course of a 24-hour recovery following exposure to smoke. Mass spectrometry identification of several significantly nitrated mitochondrial proteins revealed diverse functions and involvement in central aspects of mitochondrial physiology. The nitrated proteins include the ubiquitous mitochondrial creatine kinase, F1-ATP synthase α subunit, dihydrolipoamide dehydrogenase (E3), succinate dehydrogenase Fp subunit, and voltage-dependent anion channel (VDAC1) protein. Furthermore, acute exposure to combustion smoke significantly compromised the respiratory capacity of hippocampal mitochondria. Importantly, elevated protein nitration and reduced mitochondrial respiration in the hippocampus persisted beyond the time required for restoration of normal oxygen and carboxyhemoglobin blood levels after the cessation of exposure to smoke. Thus, the time frame for intensification of the various smoke-induced effects differs between blood and brain tissues. Taken together, our findings suggest that nitration of essential mitochondrial proteins may contribute to the reduction in mitochondrial respiratory capacity and underlie, in part, the brain pathophysiology after acute inhalation of combustion smoke

  14. Electrolytic Lesions of the Dorsal Hippocampus Disrupt Renewal of Conditional Fear after Extinction

    Science.gov (United States)

    Ji, Jinzhao; Maren, Stephen

    2005-01-01

    There is a growing body of evidence that the hippocampus is critical for context-dependent memory retrieval. In the present study, we used Pavlovian fear conditioning in rats to examine the role of the dorsal hippocampus (DH) in the context-specific expression of fear memory after extinction (i.e., renewal). Pre-training electrolytic lesions of…

  15. Contributions of Volumetrics of the Hippocampus and Thalamus to Verbal Memory in Temporal Lobe Epilepsy Patients

    Science.gov (United States)

    Stewart, Christopher C.; Griffith, H. Randall; Okonkwo, Ozioma C.; Martin, Roy C.; Knowlton, Robert K.; Richardson, Elizabeth J.; Hermann, Bruce P.; Seidenberg, Michael

    2009-01-01

    Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However,…

  16. Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus

    DEFF Research Database (Denmark)

    Hosseini-Sharifabad, Mohammad; Nyengaard, Jens Randel

    2007-01-01

    Tools recently developed in stereology were employed for unbiased estimation of the neuronal number and volume in three major subdivisions of rat hippocampus (dentate granular, CA1 and CA3 pyramidal layers). The optical fractionator is used extensively in quantitative studies of the hippocampus; ...

  17. Post-Training Reversible Inactivation of the Hippocampus Enhances Novel Object Recognition Memory

    Science.gov (United States)

    Oliveira, Ana M. M.; Hawk, Joshua D.; Abel, Ted; Havekes, Robbert

    2010-01-01

    Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory…

  18. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus

    Directory of Open Access Journals (Sweden)

    Erin C. Kerfoot

    2018-02-01

    Full Text Available The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic

  19. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.

    Science.gov (United States)

    Kerfoot, Erin C; Williams, Cedric L

    2018-01-01

    The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS) regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg) previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic modifications

  20. Reactivations of emotional memory in the hippocampus-amygdala system during sleep.

    Science.gov (United States)

    Girardeau, Gabrielle; Inema, Ingrid; Buzsáki, György

    2017-11-01

    The consolidation of context-dependent emotional memory requires communication between the hippocampus and the basolateral amygdala (BLA), but the mechanisms of this process are unknown. We recorded neuronal ensembles in the hippocampus and BLA while rats learned the location of an aversive air puff on a linear track, as well as during sleep before and after training. We found coordinated reactivations between the hippocampus and the BLA during non-REM sleep following training. These reactivations peaked during hippocampal sharp wave-ripples (SPW-Rs) and involved a subgroup of BLA cells positively modulated during hippocampal SPW-Rs. Notably, reactivation was stronger for the hippocampus-BLA correlation patterns representing the run direction that involved the air puff than for the 'safe' direction. These findings suggest that consolidation of contextual emotional memory occurs during ripple-reactivation of hippocampus-amygdala circuits.

  1. Intact renewal after extinction of conditioned suppression with lesions of either the retrosplenial cortex or dorsal hippocampus.

    Science.gov (United States)

    Todd, Travis P; Jiang, Matthew Y; DeAngeli, Nicole E; Bucci, David J

    2017-03-01

    Extinction of fear to a Pavlovian conditioned stimulus (CS) is known to be context-specific. When the CS is tested outside the context of extinction, fear returns, or renews. Several studies have demonstrated that renewal depends upon the hippocampus, although there are also studies where renewal was not impacted by hippocampal damage, suggesting that under some conditions context encoding and/or retrieval of extinction depends upon other regions. One candidate region is the retrosplenial cortex (RSC), which is known to contribute to contextual and spatial learning and memory. Using a conditioned-suppression paradigm, Experiment 1 tested the impact of pre-training RSC lesions on renewal of extinguished fear. Consistent with previous studies, lesions of the RSC did not impact acquisition or extinction of conditioned fear to the CS. Further, there was no evidence that RSC lesions impaired renewal, indicating that contextual encoding and/or retrieval of extinction does not depend upon the RSC. In Experiment 2, post-extinction lesions of either the RSC or dorsal hippocampus (DH) also had no impact on renewal. However, in Experiment 3, both RSC and DH lesions did impair performance in an object-in-place procedure, an index of place memory. RSC and DH contributions to extinction and renewal are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    Science.gov (United States)

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  3. Identification and characterization of PPARα ligands in the hippocampus.

    Science.gov (United States)

    Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J; Pahan, Kalipada

    2016-12-01

    Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions.

  4. Prevalence of Trichinella spp. in black bears, grizzly bears, and wolves in the Dehcho Region, Northwest Territories, Canada, including the first report of T. nativa in a grizzly bear from Canada.

    Science.gov (United States)

    Larter, Nicholas C; Forbes, Lorry B; Elkin, Brett T; Allaire, Danny G

    2011-07-01

    Samples of muscle from 120 black bears (Ursus americanus), 11 grizzly bears (Ursus arctos), and 27 wolves (Canis lupus) collected in the Dehcho Region of the Northwest Territories from 2001 to 2010 were examined for the presence of Trichinella spp. larvae using a pepsin-HCl digestion assay. Trichinella spp. larvae were found in eight of 11 (73%) grizzly bears, 14 of 27 (52%) wolves, and seven of 120 (5.8%) black bears. The average age of positive grizzly bears, black bears, and wolves was 13.5, 9.9, and approximately 4 yr, respectively. Larvae from 11 wolves, six black bears, and seven grizzly bears were genotyped. Six wolves were infected with T. nativa and five with Trichinella T6, four black bears were infected with T. nativa and two with Trichinella T6, and all seven grizzly bears were infected with Trichinella T6 and one of them had a coinfection with T. nativa. This is the first report of T. nativa in a grizzly bear from Canada. Bears have been linked to trichinellosis outbreaks in humans in Canada, and black bears are a subsistence food source for residents of the Dehcho region. In order to assess food safety risk it is important to monitor the prevalence of Trichinella spp. in both species of bear and their cohabiting mammalian food sources.

  5. Biological sex influences learning strategy preference and muscarinic receptor binding in specific brain regions of prepubertal rats.

    Science.gov (United States)

    Grissom, Elin M; Hawley, Wayne R; Hodges, Kelly S; Fawcett-Patel, Jessica M; Dohanich, Gary P

    2013-04-01

    According to the theory of multiple memory systems, specific brain regions interact to determine how the locations of goals are learned when rodents navigate a spatial environment. A number of factors influence the type of strategy used by rodents to remember the location of a given goal in space, including the biological sex of the learner. We recently found that prior to puberty male rats preferred a striatum-dependent stimulus-response strategy over a hippocampus-dependent place strategy when solving a dual-solution task, while age-matched females showed no strategy preference. Because the cholinergic system has been implicated in learning strategy and is known to be sexually dimorphic prior to puberty, we explored the relationship between learning strategy and muscarinic receptor binding in specific brain regions of prepubertal males and female rats. We confirmed our previous finding that at 28 days of age a significantly higher proportion of prepubertal males preferred a stimulus-response learning strategy than a place strategy to solve a dual-solution visible platform water maze task. Equal proportions of prepubertal females preferred stimulus-response or place strategies. Profiles of muscarinic receptor binding as assessed by autoradiography varied according to strategy preference. Regardless of biological sex, prepubertal rats that preferred stimulus-response strategy exhibited lower ratios of muscarinic receptor binding in the hippocampus relative to the dorsolateral striatum compared to rats that preferred place strategy. Importantly, much of the variance in this ratio was related to differences in the ventral hippocampus to a greater extent than the dorsal hippocampus. The ratios of muscarinic receptors in the hippocampus relative to the basolateral amygdala also were lower in rats that preferred stimulus-response strategy over place strategy. Results confirm that learning strategy preference varies with biological sex in prepubertal rats with males

  6. Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    Dae Young Yoo

    2016-01-01

    Full Text Available Recent evidence exists that glucose transporter 3 (GLUT3 plays an important role in the energy metabolism in the brain. Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and mRNA levels rather than tissue levels. In the present study, we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia. In the sham-operated group, GLUT3 immunoreactivity in the hippocampal CA1 region was weak, in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia, and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia, with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia. In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein (GFAP, we observed strong GLUT3 immunoreactivity in the astrocytes. GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion. In a double immunofluorescence study using GLUT3 and doublecortin (DCX, we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia. GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus. These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus.

  7. New seismograph includes filters

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-02

    The new Nimbus ES-1210 multichannel signal enhancement seismograph from EG and G geometrics has recently been redesigned to include multimode signal fillers on each amplifier. The ES-1210F is a shallow exploration seismograph for near subsurface exploration such as in depth-to-bedrock, geological hazard location, mineral exploration, and landslide investigations.

  8. Of Horse-Caterpillars and Homologies: Evolution of the Hippocampus and Its Name.

    Science.gov (United States)

    Butler, Ann B

    2017-01-01

    The hippocampus was first named in mammals based on the appearance of its gross morphological features, one end of it being fancied to resemble the head of a horse and the rest of it a silkworm, or caterpillar. A hippocampus, occupying the most medial part of the telencephalic pallium, has subsequently been identified in diverse nonmammalian taxa, but in which the "horse-caterpillar" morphology is lacking. While some strikingly similar functional similarities have been identified, questions of its homology ("sameness") across these taxa and about the very fundamental relationship of structure to function in central nervous system structures remain open. The hippocampal formation of amniotes participates in allocentric (external landmark) spatial navigation, memory, and attention to novel stimuli, and these functions generally are shared across amniotes despite variation in its morphological features. Substantially greater deviation in its morphology occurs in anamniotes, including amphibians and ray-finned fishes (actinopterygians), but its functions of allocentric spatial navigation and/or memory have been found to be preserved by studies in these taxa. Its shared functional roles cannot be used as evidence of structural homology, but given that other criteria indicate homology of the medial pallial derivative across these clades, the similar functions themselves may be regarded as homologous functions if they are based on the same cellular mechanisms and connections. The question arises as to whether the similar functions are performed by as yet undiscovered, shared morphological features or by different features that accomplish the same results via different mechanisms of neural function. © 2017 S. Karger AG, Basel.

  9. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

    DEFF Research Database (Denmark)

    Jørgensen, A.; Magnusson, P.; Hanson, Lars G.

    2016-01-01

    , and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. Results......: Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations...

  10. The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor.

    Science.gov (United States)

    Harms, Frederike L; Alawi, Malik; Amor, David J; Tan, Tiong Y; Cuturilo, Goran; Lissewski, Christina; Brinkmann, Julia; Schanze, Denny; Kutsche, Kerstin; Zenker, Martin

    2018-02-01

    Noonan syndrome is characterized by typical craniofacial dysmorphism, postnatal growth retardation, congenital heart defect, and learning difficulties and belongs to the RASopathies, a group of neurodevelopmental disorders caused by germline mutations in genes encoding components of the RAS-MAPK pathway. Mutations in the RAF1 gene are associated with Noonan syndrome, with a high prevalence of hypertrophic cardiomyopathy (HCM). RAF1 mutations cluster in exons encoding the conserved region 2 (CR2), the kinase activation segment of the CR3 domain, and the C-terminus. We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial-like leptomeningeal tumor (DOLT) of childhood at the age of 9 years. While there is a well-established association of NS with malignant tumors, especially childhood hemato-oncological diseases, brain tumors have rarely been reported in Noonan syndrome. Our data demonstrate that mutation scanning of the entire coding region of genes associated with Noonan syndrome is mandatory not to miss rare variants located outside the known mutational hotspots. © 2017 Wiley Periodicals, Inc.

  11. Connectivity of the hippocampus and Broca's area during acquisition of a novel grammar.

    Science.gov (United States)

    Kepinska, Olga; de Rover, Mischa; Caspers, Johanneke; Schiller, Niels O

    2018-01-15

    Following Opitz and Friederici (2003) suggesting interactions of the hippocampal system and the prefrontal cortex as the neural mechanism underlying novel grammar learning, the present fMRI study investigated functional connectivity of bilateral BA 44/45 and the hippocampus during an artificial grammar learning (AGL) task. Our results, contrary to the previously reported interactions, demonstrated parallel (but separate) contributions of both regions, each with their own interactions, to the process of novel grammar acquisition. The functional connectivity pattern of Broca's area pointed to the importance of coherent activity of left frontal areas around the core language processing region for successful grammar learning. Furthermore, connectivity patterns of left and right hippocampi (predominantly with occipital areas) were found to be a strong predictor of high performance on the task. Finally, increasing functional connectivity over time of both left and right BA 44/45 with the right posterior cingulate cortex and the right temporo-parietal areas points to the importance of multimodal and attentional processes supporting novel grammar acquisition. Moreover, it highlights the right-hemispheric involvement in initial stages of L2 learning. These latter interactions were found to operate irrespective of the task performance, making them an obligatory mechanism accompanying novel grammar learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Gradient-based reliability maps for ACM-based segmentation of hippocampus.

    Science.gov (United States)

    Zarpalas, Dimitrios; Gkontra, Polyxeni; Daras, Petros; Maglaveras, Nicos

    2014-04-01

    Automatic segmentation of deep brain structures, such as the hippocampus (HC), in MR images has attracted considerable scientific attention due to the widespread use of MRI and to the principal role of some structures in various mental disorders. In this literature, there exists a substantial amount of work relying on deformable models incorporating prior knowledge about structures' anatomy and shape information. However, shape priors capture global shape characteristics and thus fail to model boundaries of varying properties; HC boundaries present rich, poor, and missing gradient regions. On top of that, shape prior knowledge is blended with image information in the evolution process, through global weighting of the two terms, again neglecting the spatially varying boundary properties, causing segmentation faults. An innovative method is hereby presented that aims to achieve highly accurate HC segmentation in MR images, based on the modeling of boundary properties at each anatomical location and the inclusion of appropriate image information for each of those, within an active contour model framework. Hence, blending of image information and prior knowledge is based on a local weighting map, which mixes gradient information, regional and whole brain statistical information with a multi-atlas-based spatial distribution map of the structure's labels. Experimental results on three different datasets demonstrate the efficacy and accuracy of the proposed method.

  13. MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

    Science.gov (United States)

    Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2016-01-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

  14. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    Science.gov (United States)

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Electrophysiological and Morphological Characterization of Chrna2 Cells in the Subiculum and CA1 of the Hippocampus: An Optogenetic Investigation

    Directory of Open Access Journals (Sweden)

    Heather Nichol

    2018-02-01

    Full Text Available The nicotinic acetylcholine receptor alpha2 subunit (Chrna2 is a specific marker for oriens lacunosum-moleculare (OLM interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus. We aimed to assess the similarities between Chrna2 subiculum and CA1 neurons in terms of the expression of interneuron markers, their membrane properties, and their inhibitory input to pyramidal neurons. We found that subiculum and CA1 dorsal Chrna2 cells similarly expressed the marker somatostatin and had comparable membrane and firing properties. The somas of Chrna2 cells in both regions were found in the deepest layer with axons projecting superficially. However, subiculum Chrna2 cells displayed more extensive projections with dendrites which occupied a significantly larger area than in CA1. The post-synaptic responses elicited by Chrna2 cells in pyramidal cells of both regions revealed comparable inhibitory responses elicited by GABAA receptors and, interestingly, GABAB receptor mediated components. This study provides the first in-depth characterization of Chrna2 cells in the subiculum, and suggests that subiculum and CA1 Chrna2 cells are generally similar and may play comparable roles in both sub-regions.

  16. Analytic device including nanostructures

    KAUST Repository

    Di Fabrizio, Enzo M.; Fratalocchi, Andrea; Totero Gongora, Juan Sebastian; Coluccio, Maria Laura; Candeloro, Patrizio; Cuda, Gianni

    2015-01-01

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  17. Saskatchewan resources. [including uranium

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  18. Aerial Photography and Imagery, Ortho-Corrected, This data set includes georectified, 4 -band digital orthophotos for 213.7 square miles of the Blackwater National Wildlife Refuge and Fishing Bay WMA in Dorchester County, MD., Published in 2010, 1:2400 (1in=200ft) scale, Eastern Shore Regional GIS Cooperative.

    Data.gov (United States)

    NSGIC Regional | GIS Inventory — Aerial Photography and Imagery, Ortho-Corrected dataset current as of 2010. This data set includes georectified, 4 -band digital orthophotos for 213.7 square miles...

  19. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus.

    Science.gov (United States)

    Järvelä, Juha T; Lopez-Picon, Francisco R; Plysjuk, Anna; Ruohonen, Saku; Holopainen, Irma E

    2011-04-08

    Status epilepticus (SE) is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. SE was induced by an intraperitoneal (i.p.) injection of kainic acid (KA) in 9- and 21-day-old (P9 and P21) rats. The mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), glial-derived neurotrophic factor (GDNF), interferon gamma (IFN-γ), and transforming growth factor-beta 1 (TGF-β1) were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR). IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the postnatal rat hippocampus. In the juvenile hippocampus

  1. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2011-01-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  2. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2012-02-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  3. Experience Modulates the Effects of Histone Deacetylase Inhibitors on Gene and Protein Expression in the Hippocampus: Impaired Plasticity in Aging.

    Science.gov (United States)

    Sewal, Angila S; Patzke, Holger; Perez, Evelyn J; Park, Pul; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Fletcher, Bonnie R; Long, Jeffrey M; Rapp, Peter R

    2015-08-19

    The therapeutic potential of histone deacetylase inhibitor (HDACi) treatment has attracted considerable attention in the emerging area of cognitive neuroepigenetics. The possibility that ongoing cognitive experience importantly regulates the cell biological effects of HDACi administration, however, has not been systematically examined. In an initial experiment addressing this issue, we tested whether water maze training influences the gene expression response to acute systemic HDACi administration in the young adult rat hippocampus. Training powerfully modulated the response to HDACi treatment, increasing the total number of genes regulated to nearly 3000, including many not typically linked to neural plasticity, compared with neuroepigenetics. Copyright © 2015 the authors 0270-6474/15/3511730-14$15.00/0.

  4. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

    Directory of Open Access Journals (Sweden)

    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  5. A direct morphometric comparison of five labeling protocols for multi-atlas driven automatic segmentation of the hippocampus in Alzheimer's disease.

    Science.gov (United States)

    Nestor, Sean M; Gibson, Erin; Gao, Fu-Qiang; Kiss, Alex; Black, Sandra E

    2013-02-01

    Hippocampal volumetry derived from structural MRI is increasingly used to delineate regions of interest for functional measurements, assess efficacy in therapeutic trials of Alzheimer's disease (AD) and has been endorsed by the new AD diagnostic guidelines as a radiological marker of disease progression. Unfortunately, morphological heterogeneity in AD can prevent accurate demarcation of the hippocampus. Recent developments in automated volumetry commonly use multi-template fusion driven by expert manual labels, enabling highly accurate and reproducible segmentation in disease and healthy subjects. However, there are several protocols to define the hippocampus anatomically in vivo, and the method used to generate atlases may impact automatic accuracy and sensitivity - particularly in pathologically heterogeneous samples. Here we report a fully automated segmentation technique that provides a robust platform to directly evaluate both technical and biomarker performance in AD among anatomically unique labeling protocols. For the first time we test head-to-head the performance of five common hippocampal labeling protocols for multi-atlas based segmentation, using both the Sunnybrook Longitudinal Dementia Study and the entire Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) baseline and 24-month dataset. We based these atlas libraries on the protocols of (Haller et al., 1997; Killiany et al., 1993; Malykhin et al., 2007; Pantel et al., 2000; Pruessner et al., 2000), and a single operator performed all manual tracings to generate de facto "ground truth" labels. All methods distinguished between normal elders, mild cognitive impairment (MCI), and AD in the expected directions, and showed comparable correlations with measures of episodic memory performance. Only more inclusive protocols distinguished between stable MCI and MCI-to-AD converters, and had slightly better associations with episodic memory. Moreover, we demonstrate that protocols including more posterior

  6. Effect of intrahippocampal kainic acid injections and surgical lesions on neurotransmitters in hippocampus and septum

    Energy Technology Data Exchange (ETDEWEB)

    Fonnum, F; Walaas, I

    1978-01-01

    Local injection of kainic acid (2 ..mu..g) was accompanied by destruction of intrinsic neurons in the dorsal part of hippocampus. The lesion was accompanied by a 75% reduction in glutamate decarboxylase activity, a 60% reduction in the high affinity uptake of L-glutamate, a 40 to 60% reduction in the endogeneous levels of aspartate, glutamate and GABA and no changes in the activities of choline acetyltransferase or aromatic amino acid decarboxylase in the dorsal hippocampus. Unilateral destruction of neurons in the dorsal hippocampus was followed by a 20 to 40% reduction in the high affinity uptake of glutamate in lateral, but not in medial septum, on both sides. There was no reduction in choline acetyltransferase, glutamate decarboxylase or aromatic amino acid decarboxylase activities in the lateral or medial part of the septum. Transection of fimbria and superior fornix was accompanied by a severe reduction in choline acetyltransferase and aromatic amino acid decarboxylase activity in hippocampus, in the high affinity uptake of glutamate and in the endogenous level of glutamate in the lateral septum. The results are consistent with the concept that in the hippocampus kainic acid destroys intrinsic neurons and not afferent fibres. It seems therefore that all GABAergic fibres in the hippocampus belong to intrinsic neurons whereas glutamergic and aspartergic neurons belong partly to local neurons. The connection from the hippocampus to the lateral septum probably uses glutamate as a transmitter.

  7. Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis

    Directory of Open Access Journals (Sweden)

    Jia-nan Guo

    2017-01-01

    Full Text Available Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

  8. NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

    2018-05-26

    Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

  9. Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis

    International Nuclear Information System (INIS)

    Kim, Joong-Sun; Lee, Hae-June; Kim, Jong-Choon

    2008-01-01

    Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis. (author)

  10. Potential utilization of biomass in production of electricity, heat and transportation fuels including energy combines - Regional analyses and examples; Potentiell avsaettning av biomassa foer produktion av el, vaerme och drivmedel inklusive energikombinat - Regionala analyser och raekneexempel

    Energy Technology Data Exchange (ETDEWEB)

    Ericsson, Karin; Boerjesson, Paal

    2008-01-15

    The objective of this study is to analyse how the use of biomass may increase in the next 10-20 years in production of heat, electricity and transportation fuels in Sweden. In these analyses, the biomass is assumed to be used in a resource and cost efficient way. This means for example that the demand for heat determines the potential use of biomass in co-generation of heat and electricity and in energy combines, and that the markets for by-products determine the use of biomass in production of certain transportation fuels. The economic conditions are not analysed in this study. In the heat and electricity production sector, we make regional analyses of the potential use of biomass in production of small-scale heat, district heat, process heat in the forest industry and electricity produced in co-generation with heat in the district heating systems and forest industry. These analyses show that the use of biomass in heat and electricity production could increase from 87 TWh (the use in 2004/2005, excluding small-scale heat production with firewood) to between 113 TWh and 134 TWh, depending on the future expansion of the district heating systems. Geographically, the Stockholm province accounts for a large part of the potential increase owing to the great opportunities for increasing the use of biomass in production of district heat and CHP in this region. In the sector of transportation fuels we applied a partly different approach since we consider the market for biomass-based transportation fuels to be 'unconstrained' within the next 10-20 years. Factors that constrain the production of these fuels are instead the availability of biomass feedstock and the local conditions required for achieving effective production systems. Among the first generation biofuels this report focuses on RME and ethanol from cereals. We estimate that the domestic production of RME and ethanol could amount to up to 1.4 TWh/y and 0.7-3.8 TWh/y, respectively, where the higher figure

  11. Being Included and Excluded

    DEFF Research Database (Denmark)

    Korzenevica, Marina

    2016-01-01

    Following the civil war of 1996–2006, there was a dramatic increase in the labor mobility of young men and the inclusion of young women in formal education, which led to the transformation of the political landscape of rural Nepal. Mobility and schooling represent a level of prestige that rural...... politics. It analyzes how formal education and mobility either challenge or reinforce traditional gendered norms which dictate a lowly position for young married women in the household and their absence from community politics. The article concludes that women are simultaneously excluded and included from...... community politics. On the one hand, their mobility and decision-making powers decrease with the increase in the labor mobility of men and their newly gained education is politically devalued when compared to the informal education that men gain through mobility, but on the other hand, schooling strengthens...

  12. MLPA analysis for a panel of syndromes with mental retardation reveals imbalances in 5.8% of patients with mental retardation and dysmorphic features, including duplications of the Sotos syndrome and Williams-Beuren syndrome regions

    DEFF Research Database (Denmark)

    Kirchhoff, Maria; Bisgaard, Anne-Marie; Bryndorf, Thue

    2007-01-01

    MLPA analysis for a panel of syndromes with mental retardation (MRS-MLPA) was used for investigation of 258 mentally retarded and dysmorphic patients with normal conventional karyotypes (P064 probe set, MRC-Holland, for detection of (micro)deletions associated with 1p36-deletion, Sotos, Williams...... referred with a clinical suspicion of a specific syndrome, which was confirmed in 17 patients (21.3%). The remaining 90 patients were referred because of mental retardation and dysmorphism but without suspicion of a specific syndrome. Seven imbalances, including four duplications, were detected in these 90...

  13. Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus

    Directory of Open Access Journals (Sweden)

    Narendra Pamidi

    2014-08-01

    Full Text Available Background: Environmental enrichment (EE exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ-induced diabetic and stressed rat hippocampus. Methods: Male albino rats of Wistar strain (4-5 weeks old were grouped into normal control (NC, vehicle control (VC, diabetes (DI, diabetes + stress (DI + S, diabetes + EE (DI + E, and diabetes + stress + EE (DI + S + E groups (n = 8 in each group. Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg. Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH regions of hippocampus. Results: A significant (p < 0.001 decrease in the number of survived neurons was noticed in DI (CA1, 34.06 ± 3.2; CA3, 36.1 ± 3.62; DH, 9.83 ± 2.02 as well as DI + S (CA1, 14.03 ± 3.12; CA3, 20.27 ± 4.09; DH, 6.4 ± 1.21 group rats compared to NC rats (CA1, 53.64 ± 2.96; CA3, 62.1 ± 3.34; DH, 21.11 ± 1.03. A significant (p < 0.001 increase in the number of survived neurons was observed in DI + E (CA1, 42.3 ± 3.66; CA3, 46.73 ± 4.74; DH, 17.03 ± 2.19 and DI + S + E (CA1, 29.69 ± 4.47; CA3, 36.73 ± 3.89; DH, 12.23 ± 2.36 group rats compared to DI and DI + S groups, respectively. Conclusions: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus.

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

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

    2013-10-15

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

  15. Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet.

    Science.gov (United States)

    Navigatore-Fonzo, Lorena S; Delgado, Silvia M; Gimenez, Maria Sofia; Anzulovich, Ana C

    2014-01-01

    Alterations in enzymatic antioxidant defense systems lead to a deficit of cognitive functions and altered hippocampal synaptic plasticity. The objectives of this study were to investigate endogenous rhythms of catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as CREB1 mRNA, in the rat hippocampus, and to evaluate to which extent the vitamin A deficiency could affect those temporal patterns. Rats from control and vitamin A-deficient (VAD) groups received a diet containing 4000 IU of vitamin A/kg diet, or the same diet devoid of vitamin A, respectively, during 3 months. Rats were maintained under 12-hour-dark conditions, during 10 days before the sacrifice. Circadian rhythms of CAT, GPx, RXRγ, and CREB1 mRNA levels were determined by reverse transcriptrase polymerase chain reaction in hippocampus samples isolated every 4 hours during a 24-hour period. CAT and GPx enzymatic activities were also determined by kinetic assays. Regulatory regions of clock and antioxidant enzymes genes were scanned for E-box, RXRE, and CRE sites. E-box, RXRE, and CRE sites were found on regulatory regions of GPx and CAT genes, which display a circadian expression in the rat hippocampus. VAD phase shifted CAT, GPx, and RXRγ endogenous rhythms without affecting circadian expression of CREB1. CAT and GPx expression and enzymatic activity are circadian in the rat hippocampus. The VAD affected the temporal patterns antioxidant genes expression, probably by altering circadian rhythms of its RXR receptors and clock factors; thus, it would impair the temporal orchestration of hippocampal daily cognitive performance.

  16. Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

    Science.gov (United States)

    Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

    2011-09-09

    Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Fornix white matter is correlated with resting state functional connectivity of the thalamus and hippocampus in healthy aging but not in mild cognitive impairment- a preliminary study

    Directory of Open Access Journals (Sweden)

    Elizabeth Grace Kehoe

    2015-02-01

    Full Text Available In this study we wished to examine the relationship between the structural connectivity of the fornix, a white matter (WM tract in the limbic system which is affected in amnestic mild cognitive impairment (aMCI and Alzheimer’s disease (AD, and the resting state functional connectivity (FC of two key related subcortical structures, the thalamus and hippocampus. Twenty-two older healthy controls (HC and 18 older adults with aMCI underwent multi-modal MRI scanning. The fornix was reconstructed using constrained-spherical deconvolution (CSD-based tractography. The FC between the thalamus and hippocampus was calculated using a region-of-interest approach from which the mean time series were exacted and correlated. Diffusion tensor imaging (DTI measures of the white matter microstructure of the fornix were correlated against the Fisher Z correlation values from the FC analysis. There was no difference between the groups in the fornix white matter measures, nor in the resting state FC of the thalamus and hippocampus. We did however find that the relationship between functional and structural connectivity differed significantly between the groups. In the HCs there was a significant positive association between linear diffusion (CL in the fornix and the FC of the thalamus and hippocampus, however there was no relationship between these measures in the aMCI group. These preliminary findings suggest that in aMCI, the relationship between the functional and structural connectivity of regions of the limbic system may be significantly altered compared to healthy ageing. The combined use of DWI and fMRI may advance our understanding of neural network changes in aMCI, and elucidate subtle changes in the relationship between structural and functional brain networks.

  18. Sign-trackers have elevated myo-inositol in the nucleus accumbens and ventral hippocampus following Pavlovian conditioned approach.

    Science.gov (United States)

    Fitzpatrick, Christopher J; Perrine, Shane A; Ghoddoussi, Farhad; Galloway, Matthew P; Morrow, Jonathan D

    2016-01-04

    Pavlovian conditioned approach (PCA) is a behavioral procedure that can be used to assess individual differences in the addiction vulnerability of drug-naïve rats and identify addiction vulnerability factors. Using proton magnetic resonance spectroscopy ( 1 H-MRS) ex vivo, we simultaneously analyzed concentrations of multiple neurochemicals throughout the mesocorticolimbic system two weeks after PCA training in order to identify potential vulnerability factors to addiction in drug naïve rats for future investigations. Levels of myo-inositol (Ins), a 1 H-MRS-detectable marker of glial activity/proliferation, were increased in the nucleus accumbens (NAc) and ventral hippocampus (vHPC), but not dorsal hippocampus or medial prefrontal cortex, of sign-trackers compared to goal-trackers or intermediate responders. In addition, Ins levels positively correlated with PCA behavior in the NAc and vHPC. Because the sign-tracker phenotype is associated with increased drug-seeking behavior, these results observed in drug-naïve rats suggest that alterations in glial activity/proliferation within these regions may represent an addiction vulnerability factor. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    Science.gov (United States)

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats.

    Science.gov (United States)

    Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang

    2017-07-01

    Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.

  1. Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats.

    Science.gov (United States)

    Li, Xiao-Heng; Liu, Neng-Bao; Zhang, Min-Hai; Zhou, Yan-Ling; Liao, Jia-Wan; Liu, Xiang-Qian; Chen, Hong-Wei

    2007-04-20

    The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P < 0.05). The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group (P < 0.05). The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group (P < 0.05). Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may

  2. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    Neumaier, J.F.

    1989-01-01

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

  3. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

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    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  4. Parental care improves immunity in the seahorse (Hippocampus erectus).

    Science.gov (United States)

    Lin, Tingting; Zhang, Dong; Liu, Xin; Xiao, Dongxue

    2016-11-01

    In the present study, the sexual dimorphism in immune response in the seahorse Hippocampus erectus in which males compete for mates and invest heavily in parental care was assessed. Variability in immunocompetence in virginal seahorses with differing levels of sexual maturity (i.e., immaturity, early maturity and maturity) and with different mating statuses (i.e., virginal, experienced mating failure and experienced mating success) were analyzed by evaluating immune parameters in the plasma. Additionally, ultrastructural characteristics of the inner epithelium of the brood pouch were compared between males that had experienced mating failure and those that had succeeded. Generally, immunity in sexually mature virgin males was greater than in females, and mating competition significantly reduced males' immunity. However, parental care gave males stronger immune and metabolic abilities and resulted in their immunity significantly rebounding after a successful mating. The present study quantitatively clarifies, for the first time, how parental care and mating competition jointly affect immunity. Moreover, previous findings that females display more efficient immune defenses than males in conventional species (i.e., males are as competitor and females as care giver) and that males' immunity is higher than females' in the pipefish (i.e., females are as competitor and males as care giver) in combination with the present results indicate that parental care is a key factor for sexual dimorphism in immunity. The care-giving sex has strong immunity regardless of the sex in charge of mating competition or not. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Seahorse (Hippocampus reidi) as a bioindicator of crude oil exposure.

    Science.gov (United States)

    Delunardo, Frederico Augusto Cariello; de Carvalho, Luciano Rodrigues; da Silva, Bruno Ferreira; Galão, Michel; Val, Adalberto Luís; Chippari-Gomes, Adriana R

    2015-07-01

    This study explored the suitability of the seahorse Hippocampus reidi (Ginsburg, 1933) for assessing biomarkers of genotoxic effects and its use as a sentinel organism to detect the effects of acute exposure to petroleum hydrocarbons. Fish were exposed to three concentrations of crude oil (10, 20 and 30 g/kg) for 96 h, and the activity of phase II biotransformation enzyme glutathione S-transferase (GST) was measured. In addition, we performed genotoxicity assays, such as comet assay, micronucleus (MN) test and nuclear abnormalities (NA) induction, on the erythrocytes of the fish species. Our results revealed that the inhibition of hepatic GST activity in H. reidi was dependent on increasing crude oil concentrations. In contrast, an increase in the damage index (DI) and MN frequency were observed with increased crude oil concentrations. These results indicate that the alkaline comet assay and micronucleus test were suitable and useful in the evaluation of the genotoxicity of crude oil, which could improve determinations of the impact of oil spills on fish populations. In addition, H. reidi is a promising "sentinel organism" to detect the genotoxic impact of petroleum hydrocarbons. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Rhythmic Working Memory Activation in the Human Hippocampus

    Directory of Open Access Journals (Sweden)

    Marcin Leszczyński

    2015-11-01

    Full Text Available Working memory (WM maintenance is assumed to rely on a single sustained process throughout the entire maintenance period. This assumption, although fundamental, has never been tested. We used intracranial electroencephalography (EEG recordings from the human hippocampus in two independent experiments to investigate the neural dynamics underlying WM maintenance. We observed periodic fluctuations between two different oscillatory regimes: Periods of “memory activation” were reflected by load-dependent alpha power reductions and lower levels of cross-frequency coupling (CFC. They occurred interleaved with periods characterized by load-independent high levels of alpha power and CFC. During memory activation periods, a relevant CFC parameter (load-dependent changes of the peak modulated frequency correlated with individual WM capacity. Fluctuations between these two periods predicted successful performance and were locked to the phase of endogenous delta oscillations. These results show that hippocampal maintenance is a dynamic rather than constant process and depends critically on a hierarchy of oscillations.

  7. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    International Nuclear Information System (INIS)

    Kodavanti, Prasada Rao S.; Osorio, Cristina; Royland, Joyce E.; Ramabhadran, Ram; Alzate, Oscar

    2011-01-01

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca 2+ -mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: ► We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. ► Cerebellum and

  8. 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 affe