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Sample records for hippocampus abdominalis choosy

  1. Scuticociliatid ciliate outbreak in Australian potbellied seahorse, Hippocampus abdominalis (Lesson, 1827): clinical signs, histopathologic findings, and treatment with metronidazole.

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    Di Cicco, Emiliano; Paradis, Erika; Stephen, Craig; Turba, Maria Elena; Rossi, Giacomo

    2013-06-01

    A severe outbreak of scuticociliatosis occurred in Australian pot-bellied seahorse, Hippocampus abdominalis (Lesson, 1872), kept at the Vancouver Aquarium Marine Science Centre (Vancouver, British Columbia, Canada). Clinical signs included anorexia, lethargy, irregular respiration, and death. Cytology and histopathology revealed a high number of histophagous ciliated protozoa within the tissues. The parasite, identified as Philasterides dicentrarchi, was observed in several internal organs that appeared edematous and hemorrhagic upon postmortem examination. Severe histopathologic lesions were reported in particular in the ovary, the kidney, and the intestine. This infection was successfully treated with metronidazole via bath therapy. No further evidence of this parasite was found in the treated fish.

  2. Characterization of a 1-cysteine peroxiredoxin from big-belly seahorse (Hippocampus abdominalis); insights into host antioxidant defense, molecular profiling and its expressional response to septic conditions.

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    Godahewa, G I; Perera, N C N; Elvitigala, Don Anushka Sandaruwan; Jayasooriya, R G P T; Kim, Gi-Young; Lee, Jehee

    2016-10-01

    1-cysteine peroxiredoxin (Prx6) is an antioxidant enzyme that protects cells by detoxifying multiple peroxide species. This study aimed to describe molecular features, functional assessments and potential immune responses of Prx6 identified from the big-belly seahorse, Hippocampus abdominalis (HaPrx6). The complete ORF (666 bp) of HaPrx6 encodes a polypeptide (24 kDa) of 222 amino acids, and harbors a prominent peroxiredoxin super-family domain, a peroxidatic catalytic center, and a peroxidatic cysteine. The deduced amino acid sequence of HaPrx6 shares a relatively high amino acid sequence similarity and close evolutionary relationship with Oplegnathus fasciatus Prx6. The purified recombinant HaPrx6 protein (rHaPrx6) was shown to protect plasmid DNA in the Metal Catalyzed Oxidation (MCO) assay and, together with 1,4-Dithiothreitol (DTT), protected human leukemia THP-1 cells from extracellular H2O2-mediated cell death. In addition, quantitative real-time PCR revealed that HaPrx6 mRNA was constitutively expressed in 14 different tissues, with the highest expression observed in liver tissue. Inductive transcriptional responses were observed in liver and kidney tissues of fish after treating them with bacterial stimuli, including LPS, Edwardsiella tarda, and Streptococcus iniae. These results suggest that HaPrx6 may play an important role in the immune response of the big-belly seahorse against microbial infection. Collectively, these findings provide structural and functional insights into HaPrx6.

  3. Copper-zinc-superoxide dismutase (CuZnSOD), an antioxidant gene from seahorse (Hippocampus abdominalis); molecular cloning, sequence characterization, antioxidant activity and potential peroxidation function of its recombinant protein.

    Science.gov (United States)

    Perera, N C N; Godahewa, G I; Lee, Jehee

    2016-10-01

    Copper-zinc-superoxide dismutase (CuZnSOD) from Hippocampus abdominalis (HaCuZnSOD) is a metalloenzyme which belongs to the ubiquitous family of SODs. Here, we determined the characteristic structural features of HaCuZnSOD, analyzed its evolutionary relationships, and identified its potential immune responses and biological functions in relation to antioxidant defense mechanisms in the seahorse. The gene had a 5' untranslated region (UTR) of 67 bp, a coding sequence of 465 bp and a 3' UTR of 313 bp. The putative peptide consists of 154 amino acids. HaCuZnSOD had a predicted molecular mass of 15.94 kDa and a theoretical pI value of 5.73, which is favorable for copper binding activity. In silico analysis revealed that HaCuZnSOD had a prominent Cu-Zn_superoxide_dismutase domain, two Cu/Zn signature sequences, a putative N-glycosylation site, and several active sites including Cu(2+) and Zn(2+) binding sites. The three dimensional structure indicated a β-sheet barrel with 8 β-sheets and two short α-helical regions. Multiple alignment analyses revealed many conserved regions and active sites among its orthologs. The highest amino acid identity to HaCuZnSOD was found in Siniperca chuatsi (87.4%), while Maylandia zebra shared a close relationship in the phylogenetic analysis. Functional assays were performed to assess the antioxidant, biophysical and biochemical properties of overexpressed recombinant (r) HaCuZnSOD. A xanthine/XOD assay gave optimum results at pH 9 and 25 °C indicating these may be the best conditions for its antioxidant action in the seahorse. An MTT assay and flow cytometry confirmed that rHaCuZnSOD showed peroxidase activity in the presence of HCO3(-). In all the functional assays, the level of antioxidant activity of rHaCuZnSOD was concentration dependent; metal ion supplementation also increased its activity. The highest mRNA expressional level of HaCuZnSOD was found in blood. Temporal assessment under pathological stress showed a delay

  4. Along came a spider who sat down beside her: Perceived predation risk, but not female age, affects female mate choosiness.

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    Atwell, Ashley; Wagner, William E

    2015-06-01

    Organisms often exhibit behavioral plasticity in response to changes in factors, such as predation risk, mate density, and age. Particularly, female mate choosiness (the strength of female's attraction to male traits as they deviate from preferred trait values) has repeatedly been shown to be plastic. This is due to the costs associated with searching for preferred males fluctuating with changes in such factors. Because these factors can interact naturally, it is important to understand how female mate choosiness responds to these interactions. We studied the interaction between perceived predation risk and female age on the variable field cricket, Gryllus lineaticeps. Females were either exposed or not exposed to predation cues from a sympatric, cursorial, wolf spider predator, Hogna sp. We then tested the females at one of three adult ages and measured their choosiness by recording their responsiveness to a low quality male song. We found female choosiness plasticity was affected by neither age nor the interaction between age and perceived predation risk. Perceived predation risk was the only factor to significantly affect the plasticity of female mate choosiness: females were less choosy when they perceived predation risk and were more choosy when they did not. Predation may be such a strong source of selection that, regardless of differences in other factors, most individuals respond similarly.

  5. Extensive genetic diversity and endemism across the global range of the oceanic copepod Pleuromamma abdominalis

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    Hirai, Junya; Tsuda, Atsushi; Goetze, Erica

    2015-11-01

    Many oceanic zooplankton species have been described as cosmopolitan in distribution; however, recent molecular work has detected species complexity with highly divergent genetic lineages within several of these taxa. To further resolve the species complexity within these ecologically-important and widespread species, we performed both molecular and morphological analyses of the oceanic copepod Pleuromamma abdominalis using a comprehensive collection of material from 944 individuals collected at 46 sites across the global ocean. Phylogenetic analyses of mitochondrial cytochrome oxidase subunit I (mtCOI) sequences detected eighteen divergent evolutionary lineages within P. abdominalis, with an additional four singleton specimens that were also genetically divergent. Two phylogenetically distinct groups, PLAB1 and PLAB2, were supported by concordant sequence variation in the nuclear large subunit ribosomal RNA gene (nLSU). Within PLAB1, two mtCOI clades, 1a-1 and 1b-1 were observed, and each clade contained geographically distinct sub-clades 1a-2 and 1b-2. PLAB2 was composed of sixteen well-supported mtCOI clades (2a-2p) as well as four singletons. High genetic divergence among the mtCOI lineages within both PLAB1 and PLAB2, ranging between 9.2-11.2% and 4.3-18.9% K2P distances respectively, suggests the presence of additional species within these groups. Significant differences were observed in the presence and shape of antennule spines of adult females between sympatric clades with genetic distances greater than 5.7-7.0% (K2P). The biogeographic distributions of mtCOI clades indicated greater specialization to particular oceanographic provinces than observed in the nominal species P. abdominalis, with mtCOI clades ranging from antitropical in subtropical waters of all three ocean basins (Atlantic, Pacific and Indian; clade 1b-1 and 2a) to taxa that are endemic to a particular ocean region, for example restricted to equatorial waters of the Atlantic Ocean (clade 1b

  6. Direct and indirect sublethal effects of Galanthus nivalis agglutinin (GNA) on the development of a potato-aphid parasitoid, Aphelinus abdominalis (Hymenoptera: Aphelinidae).

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    Couty, A; de la Viña, G; Clark, S J.; Kaiser, L; Pham-Delègue, M -H.; Poppy, G M.

    2001-06-01

    Snowdrop lectin (Galanthus nivalis agglutinin, GNA), has been shown to confer partial resistance to two potato aphids Myzus persicae and Aulacorthum solani, when incorporated in artificial diet and/or expressed in transgenic potato. First-tier laboratory-scale experiments were conducted to assess the potential effect of GNA on the aphid parasitoid Aphelinus abdominalis. GNA (0.1% w/v) was successfully delivered to Macrosiphum euphorbiae via artificial diet and induced a reduced growth rate and increased mortality compared to aphids fed a control diet. As aphid parasitoid larvae are endophagous, they may be exposed to GNA during their larval development and potential "chronic toxicity" on A. abdominalis was investigated. The amounts of GNA present in aphid and parasitoid tissues were estimated by western blotting. Results suggest that parasitoids excrete most of the GNA ingested. Sublethal effects of GNA on several parasitoid fitness parameters (parasitism success, parasitoid development and size, emergence success, progeny survival and sex ratio) were studied. No direct detrimental effect of GNA on A. abdominalis was observed. However, GNA had an indirect host-size-mediated effect on the sex ratio and the size of parasitoids developing in GNA-fed aphids. This work highlights the need to determine the exact "causes and effects" when assessing the ecological impact of transgenic plants on non-target beneficial insects. Such bioassays form the basis of a tiered risk assessment moving from laboratory studies assessing individuals towards field-scale experiments assessing populations.

  7. Effects of plant protease inhibitors, oryzacystatin I and soybean Bowman-Birk inhibitor, on the aphid Macrosiphum euphorbiae (Homoptera, Aphididae) and its parasitoid Aphelinus abdominalis (Hymenoptera, Aphelinidae).

    Science.gov (United States)

    Azzouz, H; Cherqui, A; Campan, E D M; Rahbé, Y; Duport, G; Jouanin, L; Kaiser, L; Giordanengo, P

    2005-01-01

    Transgenic plants expressing protease inhibitors (PIs) have emerged in recent years as an alternative strategy for pest control. Beneficial insects such as parasitoids may therefore be exposed to these entomotoxins either via the host or by direct exposure to the plant itself. With the objective of assessing the effects of PIs towards aphid parasitoids, bioassays using soybean Bowman-Birk inhibitor (SbBBI) or oryzacystatin I (OCI) on artificial diet were performed on Macrosiphum euphorbiae-Aphelinus abdominalis system. OCI significantly reduced nymphal survival of the potato aphid M. euphorbiae and prevented aphids from reproducing. This negative effect was much more pronounced than with other aphid species. On the contrary, SbBBI did not affect nymphal viability but significantly altered adult demographic parameters. Enzymatic inhibition assays showed that digestive proteolytic activity of larvae and adults of Aphelinus abdominalis predominantly relies on serine proteases and especially on chymotrypsin-like activity. Immunoassays suggested that OCI bound to aphid proteins and accumulated in aphid tissues, whereas SbBBI remained unbound in the gut. Bioassays using M. euphorbiae reared on artificial diets supplemented with both OCI and SbBBI showed a fitness impairment of Aphelinus abdominalis that developed on intoxicated aphids. However, only SbBBI was detected in parasitoid larvae, while no PI could be detected in adult parasitoids that emerged from PI-intoxicated aphids. The potential impact of PI-expressing plants on aphid parasitoids and their combined efficiency for aphid control are discussed.

  8. Choosy moral punishers.

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    Clavien, Christine; Tanner, Colby J; Clément, Fabrice; Chapuisat, Michel

    2012-01-01

    The punishment of social misconduct is a powerful mechanism for stabilizing high levels of cooperation among unrelated individuals. It is regularly assumed that humans have a universal disposition to punish social norm violators, which is sometimes labelled "universal structure of human morality" or "pure aversion to social betrayal". Here we present evidence that, contrary to this hypothesis, the propensity to punish a moral norm violator varies among participants with different career trajectories. In anonymous real-life conditions, future teachers punished a talented but immoral young violinist: they voted against her in an important music competition when they had been informed of her previous blatant misconduct toward fellow violin students. In contrast, future police officers and high school students did not punish. This variation among socio-professional categories indicates that the punishment of norm violators is not entirely explained by an aversion to social betrayal. We suggest that context specificity plays an important role in normative behaviour; people seem inclined to enforce social norms only in situations that are familiar, relevant for their social category, and possibly strategically advantageous.

  9. Choosy moral punishers.

    Directory of Open Access Journals (Sweden)

    Christine Clavien

    Full Text Available The punishment of social misconduct is a powerful mechanism for stabilizing high levels of cooperation among unrelated individuals. It is regularly assumed that humans have a universal disposition to punish social norm violators, which is sometimes labelled "universal structure of human morality" or "pure aversion to social betrayal". Here we present evidence that, contrary to this hypothesis, the propensity to punish a moral norm violator varies among participants with different career trajectories. In anonymous real-life conditions, future teachers punished a talented but immoral young violinist: they voted against her in an important music competition when they had been informed of her previous blatant misconduct toward fellow violin students. In contrast, future police officers and high school students did not punish. This variation among socio-professional categories indicates that the punishment of norm violators is not entirely explained by an aversion to social betrayal. We suggest that context specificity plays an important role in normative behaviour; people seem inclined to enforce social norms only in situations that are familiar, relevant for their social category, and possibly strategically advantageous.

  10. Unusual arrangement and behaviour of the sex chromosomes of Aphodius (Agolius abdominalis Bonelli, 1812, and comparison with A. (A. bonvouloiri Harold, 1860 (Coleoptera: Aphodiidae

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    Robert Angus

    2009-12-01

    Full Text Available Aphodius abdominalis Bonelli, 1812 is shown to have a karyotype comprising nine pairs of autosomes and sex chromosomes which are X0 (male, XX (female. At first metaphase of meiosis the X chromosome is linked to an autosomal bivalent by a darkly staining area of the cytoplasm, resembling the Xy p arrangement typical of Aphodius species, but giving nine, rather than 10, elements in the nucleus. C-banding, which shows the centromeres, confirms this unusual arrangement. A. bonvouloiri, the only other known species of subgenus Agolius Mulsant et Rey, 1869, has a male karyotype with nine pairs of autosomes and Xy sex chromosomes. No preparations of its meiosis are available.

  11. Large-scale introduction of the Indo-Pacific damselfish Abudefduf vaigiensis into Hawai'i promotes genetic swamping of the endemic congener A. abdominalis.

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    Coleman, Richard R; Gaither, Michelle R; Kimokeo, Bethany; Stanton, Frank G; Bowen, Brian W; Toonen, Robert J

    2014-11-01

    Hybridization in the ocean was once considered rare, a process prohibited by the rapid evolution of intrinsic reproductive barriers in a high-dispersal medium. However, recent genetic surveys have prompted a reappraisal of marine hybridization as an important demographic and evolutionary process. The Hawaiian Archipelago offers an unusual case history in this arena, due to the recent arrival of the widely distributed Indo-Pacific sergeant (Abudefduf vaigiensis), which is hybridizing with the endemic congener, A. abdominalis. Surveys of mtDNA and three nuclear loci across Hawai'i (N = 396, Abudefduf abdominalis and N = 314, A. vaigiensis) reveal that hybridization is significantly higher in the human-perturbed southeast archipelago (19.8%), tapering off to 5.9% in the pristine northwest archipelago. While densities of the two species varied throughout Hawai'i, hybridization was highest in regions with similar species densities, contradicting the generalization that the rarity of one species promotes interspecific mating. Our finding of later generation hybrids throughout the archipelago invokes the possibility of genetic swamping of the endemic species. Exaptation, an adaptation with unintended consequences, may explain these findings: the endemic species has transient yellow coloration during reproduction, whereas the introduced species has yellow coloration continuously as adults, in effect a permanent signal of reproductive receptivity. Haplotype diversity is higher in Hawaiian A. vaigiensis than in our samples from the native range, indicating large-scale colonization almost certainly facilitated by the historically recent surge of marine debris. In this chain of events, marine debris promotes colonization, exaptation promotes hybridization, and introgression invokes the possible collapse of an endemic species.

  12. Serotonin Receptors in Hippocampus

    OpenAIRE

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

    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 fu...

  13. 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.

  14. Serotonin Receptors in Hippocampus

    Directory of Open Access Journals (Sweden)

    Laura Cristina Berumen

    2012-01-01

    Full Text Available 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.

  15. 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

  16. Nicotinic receptors, memory, and hippocampus.

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    Kutlu, Munir Gunes; Gould, Thomas J

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) modulate the neurobiological processes underlying hippocampal learning and memory. In addition, nicotine's ability to desensitize and upregulate certain nAChRs may alter hippocampus-dependent memory processes. Numerous studies have examined the effects of nicotine on hippocampus-dependent learning, as well as the roles of low- and high-affinity nAChRs in mediating nicotine's effects on hippocampus-dependent learning and memory. These studies suggested that while acute nicotine generally acts as a cognitive enhancer for hippocampus-dependent learning, withdrawal from chronic nicotine results in deficits in hippocampus-dependent memory. Furthermore, these studies demonstrated that low- and high-affinity nAChRs functionally differ in their involvement in nicotine's effects on hippocampus-dependent learning. In the present chapter, we reviewed studies using systemic or local injections of acute or chronic nicotine, nAChR subunit agonists or antagonists; genetically modified mice; and molecular biological techniques to characterize the effects of nicotine on hippocampus-dependent learning.

  17. Autism, amnesia, hippocampus, and learning.

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    DeLong, G R

    1992-01-01

    Autism is held to be the result of the failure of a central cognitive processor which is necessary for flexible multidimensional association of sensorial stimuli, memory, and motivational states. Failure of this processor produces rigid, invariant, rote behavior, thought and language and aberrant modulation of emotion. It is argued that this central processing function is critically dependent on the hippocampus. Thus autism is postulated to be the developmental syndrome of hippocampal dysfunction. The hippocampus is postulated to be necessary for normal development in the child of language syntax, semantics, and pragmatics; the capacity for creativity and generativity in language and behavior, and combinatorial possibilities in general; for the integration of motivational states with experience and learning; and for the construction of a complex, useful and flexible structure of meaning. These constructs may become independent of hippocampus for use, but hippocampus is still required to modify or add to them. Finally, this analysis suggests a specific hypothesis of hippocampal organization which I advance as an hypothesis: that the hippocampus can be modelled as a multidimensional system in which the unique intersection of all input dimensions is the resultant.

  18. Seasonal change in the avian hippocampus.

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    Sherry, David F; MacDougall-Shackleton, Scott A

    2015-04-01

    The hippocampus plays an important role in cognitive processes, including memory and spatial orientation, in birds. The hippocampus undergoes seasonal change in food-storing birds and brood parasites, there are changes in the hippocampus during breeding, and further changes occur in some species in association with migration. In food-storing birds, seasonal change in the hippocampus occurs in fall and winter when the cognitively demanding behaviour of caching and retrieving food occurs. The timing of annual change in the hippocampus of food-storing birds is quite variable, however, and appears not to be under photoperiod control. A variety of factors, including cognitive performance, exercise, and stress may all influence seasonal change in the avian hippocampus. The causal processes underlying seasonal change in the avian hippocampus have not been extensively examined and the more fully described hormonal influences on the mammalian hippocampus may provide hypotheses for investigating the control of hippocampal seasonality in birds.

  19. Stress, memory, and the hippocampus.

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    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.

  20. Hippocampus in health and disease: An overview

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    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.

  1. Segregating the functions of human hippocampus

    OpenAIRE

    1999-01-01

    It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning...

  2. A network convergence zone in the hippocampus.

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    Bratislav Mišić

    2014-12-01

    Full Text Available The hippocampal formation is a key structure for memory function in the brain. The functional anatomy of the brain suggests that the hippocampus may be a convergence zone, as it receives polysensory input from distributed association areas throughout the neocortex. However, recent quantitative graph-theoretic analyses of the static large-scale connectome have failed to demonstrate the centrality of the hippocampus; in the context of the whole brain, the hippocampus is not among the most connected or reachable nodes. Here we show that when communication dynamics are taken into account, the hippocampus is a key hub in the connectome. Using a novel computational model, we demonstrate that large-scale brain network topology is organized to funnel and concentrate information flow in the hippocampus, supporting the long-standing hypothesis that this region acts as a critical convergence zone. Our results indicate that the functional capacity of the hippocampus is shaped by its embedding in the large-scale connectome.

  3. Human Hippocampus Arbitrates Approach-Avoidance Conflict

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    Bach, Dominik R.; Guitart-Masip, Marc; Packard, Pau A.; Miró, Júlia; Falip, Mercè; Fuentemilla, Lluís; Dolan, Raymond J.

    2014-01-01

    Summary Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus. PMID:24560572

  4. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  5. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

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    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.

  6. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus.

    Science.gov (United States)

    Varela-Nallar, Lorena; Arredondo, Sebastian B; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C

    2015-01-01

    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.

  7. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    Science.gov (United States)

    Varela-Nallar, Lorena; Arredondo, Sebastian B.; Tapia-Rojas, Cheril; Hancke, Juan; Inestrosa, Nibaldo C.

    2015-01-01

    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. PMID:26798521

  8. 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.

  9. 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.

  10. Functional neurogenesis in the adult hippocampus

    Science.gov (United States)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  11. Memory, scene construction, and the human hippocampus.

    Science.gov (United States)

    Kim, Soyun; Dede, Adam J O; Hopkins, Ramona O; Squire, Larry R

    2015-04-14

    We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

  12. Interlamellar CA1 network in the hippocampus

    OpenAIRE

    Yang, Sunggu; Yang, Sungchil; Moreira, Thais; Hoffman, Gloria; Carlson, Greg C.; Bender, Kevin J.; Alger, Bradley E.; Tang, Cha-Min

    2014-01-01

    It has generally been thought that CA1 cells form only negligible connections with each other along the longitudinal axis of the hippocampus. But if CA1 cells were interconnected in an effective autoassociational network, this information would add a critical new dimension to our understanding of cellular processing within this structure. Here, we report the existence of a well-organized, longitudinally projecting synaptic network among CA1 pyramidal neurons. We further show that synapses of ...

  13. Attention Stabilizes Representations in the Human Hippocampus.

    Science.gov (United States)

    Aly, Mariam; Turk-Browne, Nicholas B

    2016-02-01

    Attention and memory are intricately linked, but how attention modulates brain areas that subserve memory, such as the hippocampus, is unknown. We hypothesized that attention may stabilize patterns of activity in human hippocampus, resulting in distinct but reliable activity patterns for different attentional states. To test this prediction, we utilized high-resolution functional magnetic resonance imaging and a novel "art gallery" task. On each trial, participants viewed a room containing a painting, and searched a stream of rooms for a painting from the same artist (art state) or a room with the same layout (room state). Bottom-up stimulation was the same in both tasks, enabling the isolation of neural effects related to top-down attention. Multivariate analyses revealed greater pattern similarity in all hippocampal subfields for trials from the same, compared with different, attentional state. This stability was greater for the room than art state, was unrelated to univariate activity, and, in CA2/CA3/DG, was correlated with behavior. Attention therefore induces representational stability in the human hippocampus, resulting in distinct activity patterns for different attentional states. Modulation of hippocampal representational stability highlights the far-reaching influence of attention outside of sensory systems.

  14. Proteomic analysis of hippocampus in the rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; WANG Ren-zhi; LIAN Zhi-gang; YAO Yong

    2004-01-01

    Objective To analyze the protein expression in the rat hippocampus by the proteomic approach.Methods Proteins from hippocampal tissue homogenates of the rat were separated by two-dimensional gel electrophoresis(2-DE),and stained with colloidal Coomassie blue to produce a high-resolution map of the rat hippocampus proteome.Selected proteins from this map were digested with trypsin,and the resulting tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The mass spectrometric data were used to identify the proteins through searches of the NCBI protein sequence database.Results 37 prominent proteins with various functional characteristics were identified.The identified brain protein classes covered metabolism enzymes,cytoskeleton proteins,heat shock proteins,antioxidant proteins,signalling proteins,proteasome-related proteins,neuron-specific proteins and glial-associated proteins.Furthermore,3 hypothetical proteins,unknown proteins so far only proposed from their nucleic acid structure,were identified.Conclusion This study provides the first unbiased characterization of proteins of the rat hippocampus and will be used for future studies of differential protein expression in rat models of neurological disorders.

  15. Musical Training Induces Functional Plasticity in Human Hippocampus

    OpenAIRE

    2010-01-01

    Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for ...

  16. Hippocampus size predicts fluid intelligence in musically trained people

    OpenAIRE

    Descloux, C.

    2011-01-01

    Introduction Neurogenesis persists in the human adult hippocampus1 and the survival of new progenitor cells is enhanced by learning activities2. Using the musician's brain as a model for cortical plasticity, musical training induced functional adaptations of the hippocampus have been demonstrated3,4. Furthermore, there is evidence for a positive correlation between hippocampus size and fluid intelligence5, encompassing aspects of attention, working memory and executive functions6. Previous...

  17. Hippocampus size predicts fluid intelligence in musically trained people

    OpenAIRE

    Descloux, C.

    2011-01-01

    Introduction Neurogenesis persists in the human adult hippocampus1 and the survival of new progenitor cells is enhanced by learning activities2. Using the musician's brain as a model for cortical plasticity, musical training induced functional adaptations of the hippocampus have been demonstrated3,4. Furthermore, there is evidence for a positive correlation between hippocampus size and fluid intelligence5, encompassing aspects of attention, working memory and executive functions6. Previous...

  18. GABAergic cell types in the lizard hippocampus.

    Science.gov (United States)

    Guirado, S; Dávila, J C

    1999-04-01

    The neurochemical classification of GABAergic cells in the lizard hippocampus resulted in a further division into four major, non-overlapping subtypes. Each GABAergic cell subtype displays specific targets on the principal hippocampal neurons. The synaptic targets of the GABA/neuropeptide subtype are the distal apical dendrites of principal neurons. Calretinin- and parvalbumin-containing GABAergic cells synapse on the cell body and proximal dendrites of principal cells. Calbindin is expressed in a distinct group of interneurons, the synapses of which are directed to the dendrites of principal neurons. Finally, another subtype displays NADPH-diaphorase activity, but its synaptic target has not been established.

  19. 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.

  20. Hippocampus Segmentation Based on Local Linear Mapping

    Science.gov (United States)

    Pang, Shumao; Jiang, Jun; Lu, Zhentai; Li, Xueli; Yang, Wei; Huang, Meiyan; Zhang, Yu; Feng, Yanqiu; Huang, Wenhua; Feng, Qianjin

    2017-04-01

    We propose local linear mapping (LLM), a novel fusion framework for distance field (DF) to perform automatic hippocampus segmentation. A k-means cluster method is propose for constructing magnetic resonance (MR) and DF dictionaries. In LLM, we assume that the MR and DF samples are located on two nonlinear manifolds and the mapping from the MR manifold to the DF manifold is differentiable and locally linear. We combine the MR dictionary using local linear representation to present the test sample, and combine the DF dictionary using the corresponding coefficients derived from local linear representation procedure to predict the DF of the test sample. We then merge the overlapped predicted DF patch to obtain the DF value of each point in the test image via a confidence-based weighted average method. This approach enabled us to estimate the label of the test image according to the predicted DF. The proposed method was evaluated on brain images of 35 subjects obtained from SATA dataset. Results indicate the effectiveness of the proposed method, which yields mean Dice similarity coefficients of 0.8697, 0.8770 and 0.8734 for the left, right and bi-lateral hippocampus, respectively.

  1. Association between income and the hippocampus.

    Directory of Open Access Journals (Sweden)

    Jamie L Hanson

    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.

  2. Neuroimaging studies of the hippocampus in schizophrenia.

    Science.gov (United States)

    Heckers, S

    2001-01-01

    Three neuroimaging techniques, morphometric neuroimaging, magnetic resonance spectroscopy, and functional neuroimaging, have provided evidence for abnormal hippocampal structure and function in schizophrenia. Hippocampal volume reduction is now one of the most consistent structural abnormalities found in schizophrenia: it is present at the onset of the illness and, to a lesser degree, in first-degree relatives of schizophrenic probands. Decreased levels of N-acetyl-aspartate point towards a cellular basis of such volume changes. Functional neuroimaging studies have demonstrated abnormal levels of hippocampal activity at rest, during the experience of auditory hallucinations, and during the performance of memory retrieval tasks. These results of neuroimaging studies complement evidence from post-mortem and behavioral studies, which have found regionally specific abnormalities of the hippocampus and of memory function in schizophrenia.

  3. Neuroinflammation in the normal aging hippocampus.

    Science.gov (United States)

    Barrientos, R M; Kitt, M M; Watkins, L R; Maier, S F

    2015-11-19

    A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. Here we discuss the mechanisms by which long-lasting elevations in pro-inflammatory cytokines in the hippocampus produce memory impairments. Sensitized microglia are a primary source of this exaggerated neuroinflammatory response and appear to be a hallmark of the normal aging brain. We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects.

  4. 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.

  5. 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.

  6. Mate sampling and choosiness in the sand goby.

    Science.gov (United States)

    Lindström, Kai; Lehtonen, Topi K

    2013-08-22

    To date, mate choice studies have mostly focused on establishing which mates are chosen or how the choices are performed. Here, we combined these two approaches by empirically testing how latency to mate is affected by various search costs, variation in mate quality and female quality in the sand goby (Pomatoschistus minutus). Our results show that females adjust their mating behaviour according to the costs and benefits of the choice situation. Specifically, they mated sooner when access to males was delayed and when the presence of other females presented a mate sampling cost. We also found a positive link between size variation among potential mating partners and spawning delay in some (but not all) experimental conditions. By contrast, we did not find the number of available males or the females' own body size ('quality') to affect mating latency. Finally, female mating behaviour varied significantly between years. These findings are notable for demonstrating that (i) mate sampling time is particularly sensitive to costs and, to a lesser degree, to variation among mate candidates, (ii) females' mating behaviour is sensitive to qualitative rather than to quantitative variation in their environment, and (iii) a snapshot view may describe mate sampling behaviour unreliably.

  7. Choosy but not chaste: multiple mating in human females.

    Science.gov (United States)

    Scelza, Brooke A

    2013-01-01

    When Charles Darwin set out to relate his theory of evolution by natural selection to humans he discovered that a complementary explanation was needed to properly understand the great variation seen in human behavior. The resulting work, The Descent of Man and Selection in Relation to Sex, laid out the defining principles and evidence of sexual selection. In brief, this work is best known for illuminating the typically male strategy of intrasexual competition and the typically female response of intersexual choice. While these sexual stereotypes were first laid out by Darwin, they grew in importance when, years later, A. J. Bateman, in a careful study of Drosophila mating strategies, noted that multiple mating appeared to provide great benefit to male reproductive success, but to have no such effect on females. As a result, female choice soon became synonymous with being coy, and only males were thought to gain from promiscuous behavior. However, the last thirty years of research have served to question much of the traditional wisdom about sex differences proposed by Darwin and Bateman, illuminating the many ways that women (and females more generally) can and do engage in multiple mating.

  8. Automatic and Manual Segmentation of Hippocampus in Epileptic Patients MRI

    CERN Document Server

    Hosseini, Mohammad-Parsa; Pompili, Dario; Jafari-Khouzani, Kourosh; Elisevich, Kost; Soltanian-Zadeh, Hamid

    2016-01-01

    The hippocampus is a seminal structure in the most common surgically-treated form of epilepsy. Accurate segmentation of the hippocampus aids in establishing asymmetry regarding size and signal characteristics in order to disclose the likely site of epileptogenicity. With sufficient refinement, it may ultimately aid in the avoidance of invasive monitoring with its expense and risk for the patient. To this end, a reliable and consistent method for segmentation of the hippocampus from magnetic resonance imaging (MRI) is needed. In this work, we present a systematic and statistical analysis approach for evaluation of automated segmentation methods in order to establish one that reliably approximates the results achieved by manual tracing of the hippocampus.

  9. The hippocampus: hub of brain network communication for memory.

    NARCIS (Netherlands)

    F.P. Battaglia; K. Benchenane; A. Sirota; C.M.A. Pennartz; S.I. Wiener

    2011-01-01

    A complex brain network, centered on the hippocampus, supports episodic memories throughout their lifetimes. Classically, upon memory encoding during active behavior, hippocampal activity is dominated by theta oscillations (6-10Hz). During inactivity, hippocampal neurons burst synchronously, constit

  10. Hippocampus: cognitive processes and neural representations that underlie declarative memory

    National Research Council Canada - National Science Library

    Eichenbaum, Howard

    2004-01-01

    .... Recent studies using functional brain imaging in humans and neuropsychological analyses of humans and animals with hippocampal damage have revealed some of the elemental cognitive processes mediated by the hippocampus...

  11. 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.

  12. 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.

  13. Musical training induces functional plasticity in human hippocampus.

    Science.gov (United States)

    Herdener, Marcus; Esposito, Fabrizio; di Salle, Francesco; Boller, Christian; Hilti, Caroline C; Habermeyer, Benedikt; Scheffler, Klaus; Wetzel, Stephan; Seifritz, Erich; Cattapan-Ludewig, Katja

    2010-01-27

    Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training.

  14. Hippocampus and epilepsy: Findings from human tissues.

    Science.gov (United States)

    Huberfeld, G; Blauwblomme, T; Miles, R

    2015-03-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several focal epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including temporal lobe epilepsies with hippocampal sclerosis, cortical dysplasias, epilepsies associated with tumors and developmental malformations. Slices of tissue from patients with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in the neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum, an output region, which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions and consequently suppressing interictal

  15. 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.

  16. Contextual learning requires synaptic AMPA receptor delivery in the hippocampus.

    Science.gov (United States)

    Mitsushima, Dai; Ishihara, Kouji; Sano, Akane; Kessels, Helmut W; Takahashi, Takuya

    2011-07-26

    The hippocampus plays a central role in learning and memory. Although synaptic delivery of AMPA-type glutamate receptors (AMPARs) contributes to experience-dependent synaptic strengthening, its role in hippocampus-dependent learning remains elusive. By combining viral-mediated in vivo gene delivery with in vitro patch-clamp recordings, we found that the inhibitory avoidance task, a hippocampus-dependent contextual fear-learning paradigm, delivered GluR1-containing AMPARs into CA3-CA1 synapses of the dorsal hippocampus. To block the synaptic delivery of endogenous AMPARs, we expressed a fragment of the GluR1-cytoplasmic tail (the 14-aa GluR1 membrane-proximal region with two serines mutated to phospho-mimicking aspartates: MPR-DD). MPR-DD prevented learning-driven synaptic AMPAR delivery in CA1 neurons. Bilateral expression of MPR-DD in the CA1 region of the rat impaired inhibitory avoidance learning, indicating that synaptic GluR1 trafficking in the CA1 region of the hippocampus is required for encoding contextual fear memories. The fraction of CA1 neurons that underwent synaptic strengthening positively correlated with the performance in the inhibitory avoidance fear memory task. These data suggest that the robustness of a contextual memory depends on the number of hippocampal neurons that participate in the encoding of a memory trace.

  17. Multiple repressive mechanisms in the hippocampus during memory formation.

    Science.gov (United States)

    Cho, Jun; Yu, Nam-Kyung; Choi, Jun-Hyeok; Sim, Su-Eon; Kang, SukJae Joshua; Kwak, Chuljung; Lee, Seung-Woo; Kim, Ji-il; Choi, Dong Il; Kim, V Narry; Kaang, Bong-Kiun

    2015-10-02

    Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation. Copyright © 2015, American Association for the Advancement of Science.

  18. 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

    biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy...... pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; P..., 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...

  19. 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.

  20. Transitional function of DG to CA3 in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Using single cell channel model,the transmission features of CA3-DG network in the hippocampus are investigated.The influence of the stimulation on discharge pattern of pyramidal neurons is analyzed,which shows that it starts with period spiking discharges,followed by period-doubling bifurcation to chaos,and period 3 discharge evolving into chaos,and ultimately a period of bursting discharges.Bv the synaptic model,the CA3.DG network model is constructed,which analyzes the summation of postsynaptic currents in the network,the influence of postsynaptic current on discharge rhythm as well as the mechanism of bursting discharges.The strong capacitv of spatiotemporal encoding in the network indicates the features of CA3 network during the information transmission process in the hippocampus.The modeling result with time delay of the synaptic transmission is in accordance with the experimental phenomena of action potential in the hippocampus.

  1. A fundamental oscillatory state of isolated rodent hippocampus.

    Science.gov (United States)

    Wu, Chiping; Shen, Hui; Luk, Wah Ping; Zhang, Liang

    2002-04-15

    Population neuronal rhythms of various frequencies are observed in the rodent hippocampus during distinct behavioural states. However, the question of whether the hippocampus exhibits properties of spontaneous rhythms and population synchrony in isolation has not been definitively answered. To address this, we developed a novel preparation for studying neuronal rhythms in a relatively large hippocampal tissue in vitro. We isolated the whole hippocampus from mice up to 28 days postnatal age, removing the dentate gyrus while preserving the functional CA3-to-CA1 connections. Placing the hippocampal isolate in a perfusion chamber for electrophysiological assessment extracellular recordings from the CA1 revealed rhythmic field potential of 0.5 to interneurons. Similar spontaneous field rhythms were also observed in the hippocampal isolate prepared from young gerbils and rats. Based on these data, we postulate that the spontaneous rhythms represent a fundamental oscillatory state of the hippocampal circuitry isolated from extra-hippocampal inputs.

  2. Suppression of glucocorticoid secretion enhances cholinergic transmission in rat hippocampus.

    Science.gov (United States)

    Mizoguchi, Kazushige; Shoji, Hirotaka; Ikeda, Ryuji; Tanaka, Yayoi; Maruyama, Wakako; Tabira, Takeshi

    2008-08-15

    We previously demonstrated that suppression of glucocorticoid secretion by adrenalectomy (ADX) impaired prefrontal cortex-sensitive working memory, but not reference memory. Since the cholinergic system in the hippocampus is also involved in these memories, we examined the effects of glucocorticoid suppression on cholinergic transmission in the rat hippocampus. A microdialysis study revealed that ADX did not affect the basal acetylcholine release, but enhanced the KCl-evoked response. This enhanced response was reversed by the corticosterone replacement treatment. The extracellular choline concentrations increased under both basal and KCl-stimulated conditions in the ADX rats, and these increases were also reversed by the corticosterone replacement. These results indicate that suppression of glucocorticoid secretion enhances cholinergic transmission in the hippocampus in response to stimuli. It is possible that this enhanced cholinergic transmission may not contribute to the ADX-induced working memory impairment, but it may be involved in maintenance of reference memory.

  3. The primate hippocampus: ontogeny, early insult and memory.

    Science.gov (United States)

    Bachevalier, Jocelyne; Vargha-Khadem, Faraneh

    2005-04-01

    Recent evidence suggests that in primates, as in rodents, the hippocampus shows a developmental continuum that affects memory abilities from infancy to adulthood. In primates relatively few hippocampal-dependent abilities (e.g. some aspects of recognition memory) are present in early infancy, whereas others (e.g. relational memory) begin to show adult-like characteristics around 2 years of age in monkeys and 5-7 years in humans. Profound and persistent memory loss resulting from insult to the hippocampus in infancy becomes evident in everyday behavior only later in childhood. This pattern of results suggests a maturational gradient within the medial temporal lobe memory system, with most abilities crucially dependent upon the hippocampus emerging in later stages of development, supporting a model of hierarchical organization of memory within the medial temporal lobe.

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

    Science.gov (United States)

    Züst, Marc Alain; Colella, Patrizio; Reber, Thomas Peter; Vuilleumier, Patrik; Hauf, Martinus; Ruch, Simon; Henke, Katharina

    2015-01-01

    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 retrieval. This

  5. Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.

    Science.gov (United States)

    Kazda, Tomas; Vrzal, Miroslav; Prochazka, Tomas; Dvoracek, Petr; Burkon, Petr; Pospisil, Petr; Dziacky, Adam; Nikl, Tomas; Jancalek, Radim; Slampa, Pavel; Lakomy, Radek

    2017-07-20

    Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100 % was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2 % (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2 % (P=0.005) and 10.9 % (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

  6. Anterior hippocampus: the anatomy of perception, imagination and episodic memory

    Science.gov (United States)

    Zeidman, Peter; Maguire, Eleanor A.

    2017-01-01

    The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly re-experience scenes from our past and imagine future (or even fanciful) scenarios. Recent work has shown that these cognitive functions — perception, imagination and recall of scenes and events — all engage the anterior hippocampus. Here we capitalise on new findings from functional neuroimaging to propose a model that links high-level cognitive functions to specific structures within the anterior hippocampus. PMID:26865022

  7. CHANGES OF ZINC CONTAMINATION IN HIPPOCAMPUS CELLS OF ADRENALECTOMIZED RATS

    Directory of Open Access Journals (Sweden)

    Bondaruyk О.А.

    2013-09-01

    Full Text Available Adrenalectomy causes the decline of zinc maintenance in the neurons of hippocampus and B cells of pancreas that has been observed in experiments on rats. The loss of zinc of these cells has been partly compensated by the injection of adrenalin and prednizolon to the adrenalectomized animals. The increase of zinc maintenance in these cells has been caused by the sharp-stress process due to the simultaneous physical activity and immobilization. The given data prove the participation of adrenal glands in the mechanism of zinc exchanges regulation in central (hippocampus and peripheral (cells B of pancreas zinc-containing organs of animals.

  8. Early histological maturation in the hippocampus of the guinea pig.

    Science.gov (United States)

    Nacher, J; Palop, J J; Ramirez, C; Molowny, A; Lopez-Garcia, C

    2000-06-01

    The vesicular zinc-rich synaptic systems of the principal neurons of the hippocampus are well developed in newborn guinea pigs, a precocial species. In addition, alvear and fimbrial myelinated fibers as well as significant inhibitory interneurons (i.e. somatostatin, parvalbumin and opioid immunoreactive hippocampal interneurons) are also well developed. On the contrary, neither vesicular zinc synapses nor myelinated fibers nor the above mentioned immunoreactive interneurons are detectable in newborn specimens of other related altricial species such as rats or rabbits. These data suggest that early maturation of a highly integrative center related to cognitive map building such as the hippocampus is characteristic of precocial species.

  9. 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.

  10. 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...

  11. A gene-environment study of cytoglobin in the human and rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Elfving, Betina; Müller, Heidi Kaastrup;

    2013-01-01

    Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (n......NOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression....

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  12. Developing an Animal Model of Human Amnesia: The Role of the Hippocampus

    Science.gov (United States)

    Kesner, Raymond P.; Goodrich-Hunsaker, Naomi J.

    2010-01-01

    This review summarizes a series of experiments aimed at answering the question whether the hippocampus in rats can serve as an animal model of amnesia. It is recognized that a comparison of the functions of the rat hippocampus with human hippocampus is difficult, because of differences in methodology, differences in complexity of life experiences,…

  13. 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…

  14. The Learning Hippocampus: Education and Experience-Dependent Plasticity

    Science.gov (United States)

    Wenger, Elisabeth; Lövdén, Martin

    2016-01-01

    The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

  15. Hippocampus-dependent place learning enables spatial flexibility in mice

    Directory of Open Access Journals (Sweden)

    Karl R. Kleinknecht

    2012-12-01

    Full Text Available Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners and shelter. It results from two very different strategies: (i place learning which enables for flexible way finding and (ii response learning that leads to a more rigid ‘route following’. Despite the importance of knockout techniques that are only available in mice, little is known about mice’ flexibility in spatial navigation tasks.Here we demonstrate for C57BL6/N mice in a water-cross maze that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥ 60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits.In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice.

  16. Cooperation between the Hippocampus and the Striatum during Episodic Encoding

    Science.gov (United States)

    Sadeh, Talya; Shohamy, Daphna; Levy, Dana Rubi; Reggev, Niv; Maril, Anat

    2011-01-01

    The hippocampus and the striatum are thought to play distinct roles in learning and memory, each supporting an independent memory system. A fundamental question is whether, and how, these systems interact to jointly contribute to learning and memory. In particular, it remains unknown whether the striatum contributes selectively to implicit,…

  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. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

    Science.gov (United States)

    CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993. ...

  19. 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…

  20. 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

  1. 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…

  2. Behavioral Functions of the CA3 Subregion of the Hippocampus

    Science.gov (United States)

    Kesner, Raymond P.

    2007-01-01

    From a behavioral perspective, the CA3a,b subregion of the hippocampus plays an important role in the encoding of new spatial information within short-term memory with a duration of seconds and minutes. This can easily be observed in tasks that require rapid encoding, novelty detection, one-trial short-term or working memory, and one-trial cued…

  3. 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...

  4. Cooperation between the Hippocampus and the Striatum during Episodic Encoding

    Science.gov (United States)

    Sadeh, Talya; Shohamy, Daphna; Levy, Dana Rubi; Reggev, Niv; Maril, Anat

    2011-01-01

    The hippocampus and the striatum are thought to play distinct roles in learning and memory, each supporting an independent memory system. A fundamental question is whether, and how, these systems interact to jointly contribute to learning and memory. In particular, it remains unknown whether the striatum contributes selectively to implicit,…

  5. Prolactin stimulates precursor cells in the adult mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Tara L Walker

    Full Text Available In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80% in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

  6. 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.)

  7. An event map of memory space in the hippocampus

    Science.gov (United States)

    Deuker, Lorena; Bellmund, Jacob LS; Navarro Schröder, Tobias; Doeller, Christian F

    2016-01-01

    The hippocampus has long been implicated in both episodic and spatial memory, however these mnemonic functions have been traditionally investigated in separate research strands. Theoretical accounts and rodent data suggest a common mechanism for spatial and episodic memory in the hippocampus by providing an abstract and flexible representation of the external world. Here, we monitor the de novo formation of such a representation of space and time in humans using fMRI. After learning spatio-temporal trajectories in a large-scale virtual city, subject-specific neural similarity in the hippocampus scaled with the remembered proximity of events in space and time. Crucially, the structure of the entire spatio-temporal network was reflected in neural patterns. Our results provide evidence for a common coding mechanism underlying spatial and temporal aspects of episodic memory in the hippocampus and shed new light on its role in interleaving multiple episodes in a neural event map of memory space. DOI: http://dx.doi.org/10.7554/eLife.16534.001 PMID:27710766

  8. Proposed glucocorticoid-mediated zinc signaling in the hippocampus.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna

    2012-07-01

    Corticosteroid hormones are secreted from the adrenal glands in hourly pulses and signal the hippocampus for the development and function. In contrast, the stress-induced rise in corticosteroid concentrations has a profound effect on emotional arousal, motivational processes and cognitive performance. This rise is required as the stress response to maintain homeostasis in the living body or restore it. However, abnormal rise in corticosteroid concentrations is a disadvantage to the hippocampus. Corticosteroid-glutamatergic interactions during information processing are proposed as a potential model to explain many of the diverse actions of corticosteroids in synaptic plasticity such as long-term potentiation and cognition. Because zincergic neurons are a subtype of glutamatergic neurons and release Zn(2+) and glutamate into the synaptic cleft, it is possible that homeostasis of synaptic Zn(2+), in addition to homeostasis of glutamate, is modified by glucocorticoids, followed by the changes in cognitive function and stress response. Zn(2+) signal participates in cognitive and emotional behavior in cooperation with signaling of glucocorticoids and glutamate, while can disadvantageously act on the hippocampus under sever stress circumstances. This paper analyzes the actions of glucocorticoid-mediated Zn(2+) signal in the hippocampus under stressful circumstances and its significance in both hippocampal function and dysfunction.

  9. Comparison of automated and manual segmentation of hippocampus MR images

    Science.gov (United States)

    Haller, John W.; Christensen, Gary E.; Miller, Michael I.; Joshi, Sarang C.; Gado, Mokhtar; Csernansky, John G.; Vannier, Michael W.

    1995-05-01

    The precision and accuracy of area estimates from magnetic resonance (MR) brain images and using manual and automated segmentation methods are determined. Areas of the human hippocampus were measured to compare a new automatic method of segmentation with regions of interest drawn by an expert. MR images of nine normal subjects and nine schizophrenic patients were acquired with a 1.5-T unit (Siemens Medical Systems, Inc., Iselin, New Jersey). From each individual MPRAGE 3D volume image a single comparable 2-D slice (matrix equals 256 X 256) was chosen which corresponds to the same coronal slice of the hippocampus. The hippocampus was first manually segmented, then segmented using high dimensional transformations of a digital brain atlas to individual brain MR images. The repeatability of a trained rater was assessed by comparing two measurements from each individual subject. Variability was also compared within and between subject groups of schizophrenics and normal subjects. Finally, the precision and accuracy of automated segmentation of hippocampal areas were determined by comparing automated measurements to manual segmentation measurements made by the trained rater on MR and brain slice images. The results demonstrate the high repeatability of area measurement from MR images of the human hippocampus. Automated segmentation using high dimensional transformations from a digital brain atlas provides repeatability superior to that of manual segmentation. Furthermore, the validity of automated measurements was demonstrated by a high correlation with manual segmentation measurements made by a trained rater. Quantitative morphometry of brain substructures (e.g. hippocampus) is feasible by use of a high dimensional transformation of a digital brain atlas to an individual MR image. This method automates the search for neuromorphological correlates of schizophrenia by a new mathematically robust method with unprecedented sensitivity to small local and regional differences.

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

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    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

  11. Differences in relative hippocampus volume and number of hippocampus neurons among five corvid species.

    Science.gov (United States)

    Gould, Kristy L; Gilbertson, Karl E; Hrvol, Andrew J; Nelson, Joseph C; Seyfer, Abigail L; Brantner, Rose M; Kamil, Alan C

    2013-01-01

    The relative size of the avian hippocampus (Hp) has been shown to be related to spatial memory and food storing in two avian families, the parids and corvids. Basil et al. [Brain Behav Evol 1996;47:156-164] examined North American food-storing birds in the corvid family and found that Clark's nutcrackers had a larger relative Hp than pinyon jays and Western scrub jays. These results correlated with the nutcracker's better performance on most spatial memory tasks and their strong reliance on stored food in the wild. However, Pravosudov and de Kort [Brain Behav Evol 2006;67:1-9] raised questions about the methodology used in the 1996 study, specifically the use of paraffin as an embedding material and recalculation for shrinkage. Therefore, we measured relative Hp volume using gelatin as the embedding material in four North American species of food-storing corvids (Clark's nutcrackers, pinyon jays, Western scrub jays and blue jays) and one Eurasian corvid that stores little to no food (azure-winged magpies). Although there was a significant overall effect of species on relative Hp volume among the five species, subsequent tests found only one pairwise difference, blue jays having a larger Hp than the azure-winged magpies. We also examined the relative size of the septum in the five species. Although Shiflett et al. [J Neurobiol 2002;51:215-222] found a difference in relative septum volume amongst three species of parids that correlated with storing food, we did not find significant differences amongst the five species in relative septum. Finally, we calculated the number of neurons in the Hp relative to body mass in the five species and found statistically significant differences, some of which are in accord with the adaptive specialization hypothesis and some are not.

  12. Α2 GABAA receptor sub-units in the ventral hippocampus and α5 GABAA receptor sub-units in the dorsal hippocampus mediate anxiety and fear memory.

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    McEown, K; Treit, D

    2013-11-12

    Temporary neuronal inactivation of the ventral hippocampus with the GABAA agonist muscimol suppresses unconditioned fear behavior (anxiety) but inactivation of the dorsal hippocampus does not. On the other hand, inactivating the dorsal hippocampus disrupts fear memory, while inactivating the ventral hippocampus does not. Here we investigate the roles of hippocampal GABAA receptor sub-units in mediating these anxiolytic and amnesic effects of GABAA receptor agonists. We microinfused TPA023 (α2 agonist) or TB-21007 (inverse α5 agonist) into the dorsal or ventral hippocampus prior to testing rats in two animal models of anxiety: the elevated plus-maze and shock-probe burying test. Twenty-four hours later rats were re-tested in the shock-probe chamber with a non-electrified probe to assess their memory of the initial shock-probe experience (i.e., fear memory). We found that TPA023 was anxiolytic in the plus-maze and shock-probe burying tests when microinfused into the ventral hippocampus. However, TPA023 did not affect anxiety-related behavior when infused into the dorsal hippocampus. Conversely, we found that the α5 sub-unit inverse agonist TB-21007 impaired rats' memory of the initial shock-probe experience when infused into the dorsal hippocampus, but not when infused into the ventral hippocampus. This double dissociation suggests that α2 GABAA receptor sub-units in the ventral hippocampus mediate unconditioned fear or anxiety, while α5 GABAA receptor sub-units in the dorsal hippocampus mediate conditioned fear memory.

  13. 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.

  14. 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.

  15. Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus.

    Science.gov (United States)

    Brady, R J; Swann, J W

    1986-08-29

    The role of excitatory amino acid neurotransmission in epileptogenesis was investigated in the developing hippocampus. Bath application of ketamine blocked penicillin-induced, synchronized afterdischarges in immature rat CA3 hippocampal neurons. Ketamine also decreased the duration of the preceding intracellularly recorded depolarization shift but had no measurable effect on the resting membrane potential or input impedance of pyramidal cells. Concentrations of ketamine that blocked afterdischarge generation dramatically depressed intracellular depolarizations produced by iontophoretic application of N-methyl-D-aspartate (NMDA) but not quisqualate. The effects of the NMDA antagonist 2-amino-7-phosphonoheptanoic acid on epileptiform discharges were identical to those of ketamine. These results suggest that an endogenous excitatory amino acid acting on an NMDA receptor plays a key role in the pronounced capacity of immature hippocampus for seizures.

  16. Dual role of GABA in the neonatal rat hippocampus.

    Science.gov (United States)

    Khalilov, I; Dzhala, V; Ben-Ari, Y; Khazipov, R

    1999-11-01

    The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.

  17. 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.

  18. Function of hippocampus in "insight" of problem solving.

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    Luo, Jing; Niki, Kazuhisa

    2003-01-01

    Since the work of Wolfgang Kohler, the process of "insight" in problem solving has been the subject of considerable investigation. Yet, the neural correlates of "insight" remain unknown. Theoretically, "insight" means the reorientation of one's thinking, including breaking of the unwarranted "fixation" and forming of novel, task-related associations among the old nodes of concepts or cognitive skills. Processes closely related to these aspects have been implicated in the hippocampus. In this research, the neural correlates of "insight" were investigated using Japanese riddles, by imaging the answer presentation and comprehension events, just after participants failed to resolve them. The results of event-related functional magnetic resonance imaging (fMRI) analysis demonstrated that the right hippocampus was critically highlighted and that a wide cerebral cortex was also involved in this "insight" event. To the best of our knowledge, this work is the first neuroimaging study to have investigated the neural correlates of "insight" in problem solving.

  19. Prospective representation of navigational goals in the human hippocampus.

    Science.gov (United States)

    Brown, Thackery I; Carr, Valerie A; LaRocque, Karen F; Favila, Serra E; Gordon, Alan M; Bowles, Ben; Bailenson, Jeremy N; Wagner, Anthony D

    2016-06-10

    Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning.

  20. 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.

  1. Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus

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    Klein, Barbara; Mrowetz, Heike; Thalhamer, Josef; Scheiblhofer, Sandra; Weiss, Richard; Aigner, Ludwig

    2016-01-01

    Allergies and their characteristic TH2-polarized inflammatory reactions affect a substantial part of the population. Since there is increasing evidence that the immune system modulates plasticity and function of the central nervous system (CNS), we investigated the effects of allergic lung inflammation on the hippocampus—a region of cellular plasticity in the adult brain. The focus of the present study was on microglia, the resident immune cells of the CNS, and on hippocampal neurogenesis, i.e., the generation of new neurons. C57BL/6 mice were sensitized with a clinically relevant allergen derived from timothy grass pollen (Phl p 5). As expected, allergic sensitization induced high serum levels of allergen-specific immunoglobulins (IgG1 and IgE) and of TH2 cytokines (IL-5 and IL-13). Surprisingly, fewer Iba1+ microglia were found in the granular layer (GL) and subgranular zone (SGZ) of the hippocampal dentate gyrus and also the number of Iba1+MHCII+ cells was lower, indicating a reduced microglial surveillance and activation in the hippocampus of allergic mice. Neurogenesis was analyzed by labeling of proliferating cells with bromodeoxyuridine (BrdU) and determining their fate 4 weeks later, and by quantitative analysis of young immature neurons, i.e., cells expressing doublecortin (DCX). The number of DCX+ cells was clearly increased in the allergy animals. Moreover, there were more BrdU+ cells present in the hippocampus of allergic mice, and these newly born cells had differentiated into neurons as indicated by a higher number of BrdU+NeuN+ cells. In summary, allergy led to a reduced microglia presence and activity and to an elevated level of neurogenesis in the hippocampus. This effect was apparently specific to the hippocampus, as we did not observe these alterations in the subventricular zone (SVZ)/olfactory bulb (OB) system, also a region of high cellular plasticity and adult neurogenesis. PMID:27445696

  2. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus

    OpenAIRE

    2015-01-01

    Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the...

  3. Perforant path transection induces complement C9 deposition in hippocampus.

    Science.gov (United States)

    Johnson, S a; Young-Chan, C S; Laping, N J; Finch, C E

    1996-04-01

    The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells in affected brain regions during Alzheimer disease (AD) provided a basis for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs during AD. Immunostaining for C9, a key terminal component of the complement cascade membrane attack complex (MAC), showed extracellular C9 deposition in parenchyma around the EC wound and in hippocampus as early as 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, apoptotic EC layer II neurons were not immunostained by anti-rat C9 antibody, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was localized to the dentate gyrus middle molecular layer, a region of synaptic loss, dendritic degeneration, and early synaptogenesis. In addition, intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the MAC that is up-regulated in AD, was also detected in the wound area (extracellular), the dentate gyrus middle molecular layer (extracellular), and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participates in responses to brain injury, as well as in AD.

  4. Antioxidant activity of Citrus limon essential oil in mouse hippocampus.

    Science.gov (United States)

    Campêlo, Lidianne Mayra Lopes; Gonçalves, Fabrício Custódio Moura; Feitosa, Chistiane Mendes; de Freitas, Rivelilson Mendes

    2011-07-01

    Citrus limon (L.) Burms (Rutaceae) has been shown in previous studies to have various biological functions (anti-inflammatory, antiallergic, antiviral, antimutagenic, and anticarcinogenic). However, traditional uses in folk medicine suggest that C. limon may have an effect on the central nervous system (CNS). This study investigated the effects of C. limon essential oil (EO) on lipid peroxidation level, nitrite content, glutathione reduced (GSH) concentration, and antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)] activities in mice hippocampus. Swiss mice were treated with the suspension of 0.5% Tween 80, in distilled water used as vehicle (i.p., control group) and with EO in three different doses (0.05, 0.1, or 0.15 g/kg, i.p., EO 50, EO 100, and EO 150 groups, respectively). After the treatments, all groups were observed for 24 h. The enzyme activities as well as the lipid peroxidation, nitrite, and GSH concentrations in mice hippocampus were measured using spectrophotometric methods and the results were compared with values obtained from control group. EO of C. limon treatment significantly reduced the lipid peroxidation level and nitrite content but increased the GSH levels and the SOD, catalase, and GPx activities in mice hippocampus. Our findings strongly support the hypothesis that oxidative stress in hippocampus can occur during neurodegenerative diseases, proving that hippocampal damage induced by the oxidative process plays a crucial role in brain disorders, and also imply that a strong protective effect could be achieved using EO of C. limon as an antioxidant.

  5. 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

  6. 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.

  7. The role of the hippocampus in memory and mental construction.

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    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.

  8. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

    Science.gov (United States)

    Montagne, Axel; Barnes, Samuel R.; Sweeney, Melanie D.; Halliday, Matthew R.; Sagare, Abhay P.; Zhao, Zhen; Toga, Arthur W.; Jacobs, Russell E.; Liu, Collin Y.; Amezcua, Lilyana; Harrington, Michael G.; Chui, Helena C.; Law, Meng; Zlokovic, Berislav V.

    2014-01-01

    Summary The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced magnetic resonance imaging protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. PMID:25611508

  9. Immune response gene expression increases in the aging murine hippocampus.

    Science.gov (United States)

    Terao, Akira; Apte-Deshpande, Anjali; Dousman, Linda; Morairty, Stephen; Eynon, Barrett P; Kilduff, Thomas S; Freund, Yvonne R

    2002-11-01

    Using GeneChips, basal and lipopolysaccharide (LPS)-induced gene expression was examined in the hippocampus of 3-, 12-, 18- and 24-month-old male C57BL/6 mice to identify genes whose altered expression could influence hippocampal function in advanced age. Gene elements that changed with age were selected with a t-statistic and specific expression patterns were confirmed with real-time quantitative PCR. Basal expression of 128 gene elements clearly changed with age in the hippocampus. Fourteen gene elements showed increased expression with age and these increases were validated after LPS stimulation. Major histocompatibility complex (MHC) TL region and thymic shared antigen (TSA-1) gene expression increased, suggesting T cell activation in the hippocampus with age. Cytokine (interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha) and chemokine (macrophage chemotactic protein-1) expression increased sharply in 24-month-old mice. These findings are in contrast to a decrease in the peripheral immune response, documented by decreased T cell proliferation and decreased ratios of naive to memory T cells. Age-related increases in inflammatory potential in the brain may contribute to neurodegenerative diseases of the aged.

  10. Which computational mechanisms operate in the hippocampus during novelty detection?

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    Kumaran, Dharshan; Maguire, Eleanor A

    2007-01-01

    A fundamental property of adaptive behavior is the ability to rapidly distinguish what is novel from what is familiar in our environment. Empirical evidence and computational work have provided biologically plausible models of the neural substrate and mechanisms underlying the coding of stimulus novelty in the perirhinal cortex. In this article, we highlight the importance of a different category of novelty, namely associative novelty, which has received relatively little attention, despite its clear ecological importance. While previous studies in both animals and humans have documented hippocampal responses in relation to associative novelty, a key issue concerning the computations underlying these novelty signals has not been previously addressed. We argue that this question has importance not only for our understanding of novelty processing, but also for advancing our knowledge of the fundamental computational operations performed by the hippocampus. We suggest a different approach to this problem, and discuss recent evidence supporting the hypothesis that the hippocampus operates as a comparator during the processing of associative novelty, generating mismatch/novelty signals when prior predictions are violated by sensory reality. We also draw on conceptual similarities between associative novelty and contextual novelty to suggest that empirical findings from these two seemingly distant research fields accord with the operation of a comparator mechanism during novelty detection more generally. We therefore conclude that a comparator mechanism may underlie the role of the hippocampus not only in detecting occurrences that are unexpected given specific associatively retrieved predictions, but also events that violate more abstract properties of the experimental context.

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

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    Daniel Reyes-Haro

    2016-01-01

    Full Text Available 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.

  12. Neonatal Amygdala or Hippocampus Lesions Influence Responsiveness to Objects

    Science.gov (United States)

    Bliss-Moreau, Eliza; Toscano, Jessica E.; Bauman, Melissa; Mason, William A.; Amaral, David G.

    2015-01-01

    Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at two weeks of age and sham-operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala-lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus-lesioned animals’ propensity for exploration mirrored that of control animals in some contexts but amygdala-lesioned animals in other contexts. At 18 months of age, both amygdala-lesioned and hippocampus-lesioned animals were judged to be less fearful than controls during the testing procedure. Implications for understanding the neurobiology of emotional behavior are discussed. PMID:20583145

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

    Science.gov (United States)

    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. PMID:27579183

  14. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  15. Spatial memory and the monkey hippocampus: not all space is created equal.

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    Banta Lavenex, Pamela; Lavenex, Pierre

    2009-01-01

    Studies of the role of the monkey hippocampus in spatial learning and memory, however few, have reliably produced inconsistent results. Whereas the role of the hippocampus in spatial learning and memory has been clearly established in rodents, studies in nonhuman primates have made a variety of claims that range from the involvement of the hippocampus in spatial memory only at relatively longer memory delays, to no role for the hippocampus in spatial memory at all. In contrast, we have shown that selective damage restricted to the hippocampus (CA regions) prevents the learning or use of allocentric, spatial relational representations of the environment in freely behaving adult monkeys tested in an open-field arena. In this commentary, we discuss a unifying framework that explains these apparently discrepant results regarding the role of the monkey hippocampus in spatial learning and memory. We describe clear and strict criteria to interpret the findings from previous studies and guide future investigations of spatial memory in monkeys. Specifically, we affirm that, as in the rodent, the primate hippocampus is critical for spatial relational learning and memory, and in a time-independent manner. We describe how claims to the contrary are the result of experimental designs that fail to recognize, and control for, egocentric (hippocampus-independent) and allocentric (hippocampus-dependent) spatial frames of reference. Finally, we conclude that the available data demonstrate unequivocally that the central role of the hippocampus in allocentric, spatial relational learning and memory is conserved among vertebrates, including nonhuman primates.

  16. [The study on the relationship between hippocampus neuronal apoptosis and hippocampus synaptic plasticity in rats exposed to aluminum].

    Science.gov (United States)

    Nie, Xiaohan; Qin, Xiujun; Zhang, Huifang; Kang, Pan; Li, Zhaoyang; Niu, Qiao

    2015-07-01

    To investigate the effect of aluminum exposure on neuronal apoptosis of rats hippocampus and the correlation of and synaptic plasticity. There were 40 SPF grade SD rats which were randomly divided into four groups: the control group, the low dose group, the medium dose group and the high dose group, 10 rats in each group. The rats were daily gavaged with aluminum lactate for 30 days. The hippocampal fEPSPs in rat was measured by electrophysiological grapher and the neuronal apoptosis in hippocampus was detected by Flow cytometer. In addition, the relative expression of gene which includes caspase-3, 8, 9 was measured by Real-time PCR. Compared to the control group, the average of fEPSPs which after HFS 10, 20, 30, 40, 50, 60 min was decreased at different time point in the low dose group, the medium dose group and the high dose group (P neuronal apoptosis in rats, and then affect hippocampal synaptic plasticity.

  17. 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

  18. The hippocampus is necessary for enhancements and impairments of learning following stress

    OpenAIRE

    Bangasser, Debra A.; Shors, Tracey J.

    2007-01-01

    The hippocampus is often considered to be an important site for stress and learning interactions; however, it has never been demonstrated whether these effects require the hippocampus. In the current study, hippocampal lesions prevented both enhancements of learning after stress in male rats and impairments of learning after stress in female rats without disrupting learning itself in either sex. Thus, the hippocampus is necessary for modifying learning in males and females after acute stressf...

  19. Choline acetyltransferase in the hippocampus is associated with learning strategy preference in adult male rats.

    Science.gov (United States)

    Hawley, Wayne R; Witty, Christine F; Daniel, Jill M; Dohanich, Gary P

    2015-08-01

    One principle of the multiple memory systems hypothesis posits that the hippocampus-based and striatum-based memory systems compete for control over learning. Consistent with this notion, previous research indicates that the cholinergic system of the hippocampus plays a role in modulating the preference for a hippocampus-based place learning strategy over a striatum-based stimulus--response learning strategy. Interestingly, in the hippocampus, greater activity and higher protein levels of choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine, are associated with better performance on hippocampus-based learning and memory tasks. With this in mind, the primary aim of the current study was to determine if higher levels of ChAT and the high-affinity choline uptake transporter (CHT) in the hippocampus were associated with a preference for a hippocampus-based place learning strategy on a task that also could be solved by relying on a striatum-based stimulus--response learning strategy. Results confirmed that levels of ChAT in the dorsal region of the hippocampus were associated with a preference for a place learning strategy on a water maze task that could also be solved by adopting a stimulus-response learning strategy. Consistent with previous studies, the current results support the hypothesis that the cholinergic system of the hippocampus plays a role in balancing competition between memory systems that modulate learning strategy preference.

  20. Asymmetric behaviours of brain oscillations in the human hippocampus during spatial navigation tasks.

    Science.gov (United States)

    Kang, Joong Koo; Lee, Eun Mi; Kim, Dajeong; Hye Lee, Seong; Kim, Taekyung; Park, Young Min; Park, Jinsick; Kim, Sun I; Kim, In Young; Jang, Dong Pyo

    2016-02-10

    Hippocampal-dependent memory functions may be lateralized to the right hippocampus during spatial navigation. However, direct electrophysiological evidence supporting these findings in the bilateral hippocampi during spatial navigation has not been well documented in humans. We studied changes in brain oscillations between the dominant and the nondominant hippocampi during encoding periods of environmental novelty using spatial navigation tasks. Results showed that brain oscillations during the encoding period of spatial navigation increased significantly in the nondominant hippocampus compared with the dominant hippocampus. These findings provide direct electrophysiological evidence that the nondominant hippocampus plays a predominant role in spatial navigation.

  1. Intracranial EEG correlates of implicit relational inference within the hippocampus.

    Science.gov (United States)

    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

  2. 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.)

  3. 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

  4. Nonlinear frequency-dependent synchronization in the developing hippocampus.

    Science.gov (United States)

    Prida, L M; Sanchez-Andres, J V

    1999-07-01

    Synchronous population activity is present both in normal and pathological conditions such as epilepsy. In the immature hippocampus, synchronous bursting is an electrophysiological conspicuous event. These bursts, known as giant depolarizing potentials (GDPs), are generated by the synchronized activation of interneurons and pyramidal cells via GABAA, N-methyl-D-aspartate, and AMPA receptors. Nevertheless the mechanism leading to this synchronization is still controversial. We have investigated the conditions under which synchronization arises in developing hippocampal networks. By means of simultaneous intracellular recordings, we show that GDPs result from local cooperation of active cells within an integration period prior to their onset. During this time interval, an increase in the number of excitatory postsynaptic potentials (EPSPs) takes place building up full synchronization between cells. These EPSPs are correlated with individual action potentials simultaneously occurring in neighboring cells. We have used EPSP frequency as an indicator of the neuronal activity underlying GDP generation. By comparing EPSP frequency with the occurrence of synchronized GDPs between CA3 and the fascia dentata (FD), we found that GDPs are fired in an all-or-none manner, which is characterized by a specific threshold of EPSP frequency from which synchronous GDPs emerge. In FD, the EPSP frequency-threshold for GDP onset is 17 Hz. GDPs are triggered similarly in CA3 by appropriate periodic stimulation of mossy fibers. The frequency threshold for CA3 GDP onset is 12 Hz. These findings clarify the local mechanism of synchronization underlying bursting in the developing hippocampus, indicating that GDPs are fired when background levels of EPSPs or action potentials have built up full synchronization by firing at specific frequencies (>12 Hz). Our results also demonstrate that spontaneous EPSPs and action potentials are important for the initiation of synchronous bursts in the

  5. Differential vulnerability of interneurons in the epileptic hippocampus

    Directory of Open Access Journals (Sweden)

    Markus eMarx

    2013-10-01

    Full Text Available The loss of hippocampal interneurons has been considered one reason for the onset of temporal lobe epilepsy (TLE by shifting the excitation-inhibition balance. Yet, there are many different interneuron types which show differential vulnerability in the context of an epileptogenic insult. We used the intrahippocampal kainate (KA mouse model for TLE in which a focal, unilateral KA injection induces status epilepticus (SE followed by development of granule cell dispersion (GCD and hippocampal sclerosis surrounding the injection site but not in the intermediate and temporal hippocampus. In this study, we characterized the loss of interneurons with respect to septotemporal position and to differential vulnerability of interneuron populations. To this end, we performed intrahippocampal recordings of the initial SE, in situ hybridization for glutamic acid decarboxylase 67 (GAD67 mRNA and immunohistochemistry for parvalbumin (PV and neuropeptide Y (NPY in the early phase of epileptogenesis at 2 days and at 21 days after KA injection, when recurrent epileptic activity and GCD have fully developed. We show that SE extended along the entire septotemporal axis of both hippocampi, but was stronger at distant sites than at the injection site. There was an almost complete loss of interneurons surrounding the injection site and expanding to the intermediate hippocampus already at 2 days but increasing until 21 days. We observed differential vulnerability of PV- and NPY-expressing cells: while the latter were lost at the injection site but preserved at intermediate sites, PV-expressing cells were gone even at sites more temporal than GCD. In addition, we found upregulation of GAD67 mRNA expression in dispersed granule cells and of NPY staining in ipsilateral granule cells and ipsi- and contralateral mossy fibers. Our data thus indicate differential survival capacity of interneurons in the epileptic hippocampus and compensatory mechanisms depending on the

  6. 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.

  7. Intrinsic cholinergic neurons in the hippocampus: fact or artefact?

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    Jan Krzysztof Blusztajn

    2016-03-01

    Full Text Available It is generally agreed that hippocampal acetylcholine (ACh is synthesized and released exclusively from the terminals of the long-axon afferents whose cell bodies reside in the medial septum and diagonal band. The search for intrinsic cholinergic neurons in the hippocampus has a long history; however evidence for the existence of these neurons has been inconsistent, with most investigators failing to detect them using in situ hybridization or immunohistochemical staining of the cholinergic markers, choline acetyltransferase (CHAT or vesicular acetylcholine transporter (VACHT. Advances in the use of bacterial artificial chromosome (BAC transgenic mice expressing a reporter protein under the control of the genomic elements of the Chat gene (Chat-BAC mice have facilitated studies of cholinergic neurons. Such mice show robust and faithful expression of the reporter proteins in all known cholinergic cell populations. The availability of the Chat-BAC mice re-ignited interest in hippocampal cholinergic interneurons, because a small number of such reporter-expressing cells is frequently observed in the hippocampus of these mice. However, to date, attempts to confirm that these neurons co-express the endogenous cholinergic markers CHAT or VACHT, or release ACh, have been unsuccessful. Without such confirmatory evidence it is best to conclude that there are no cholinergic neurons in the hippocampus. Similar considerations apply to other BAC transgenic lines, whose utility as a discovery tool for cell populations heretofore not known to express the genes of interest encoded by the BACs, must be validated by methods that detect expression of the endogenous genes.

  8. Differential vulnerability of interneurons in the epileptic hippocampus.

    Science.gov (United States)

    Marx, Markus; Haas, Carola A; Häussler, Ute

    2013-01-01

    The loss of hippocampal interneurons has been considered as one reason for the onset of temporal lobe epilepsy (TLE) by shifting the excitation-inhibition balance. Yet, there are many different interneuron types which show differential vulnerability in the context of an epileptogenic insult. We used the intrahippocampal kainate (KA) mouse model for TLE in which a focal, unilateral KA injection induces status epilepticus (SE) followed by development of granule cell dispersion (GCD) and hippocampal sclerosis surrounding the injection site but not in the intermediate and temporal hippocampus. In this study, we characterized the loss of interneurons with respect to septotemporal position and to differential vulnerability of interneuron populations. To this end, we performed intrahippocampal recordings of the initial SE, in situ hybridization for glutamic acid decarboxylase 67 (GAD67) mRNA and immunohistochemistry for parvalbumin (PV) and neuropeptide Y (NPY) in the early phase of epileptogenesis at 2 days and at 21 days after KA injection, when recurrent epileptic activity and GCD have fully developed. We show that SE extended along the entire septotemporal axis of both hippocampi, but was stronger at distant sites than at the injection site. There was an almost complete loss of interneurons surrounding the injection site and expanding to the intermediate hippocampus already at 2 days but increasing until 21 days after KA. Furthermore, we observed differential vulnerability of PV- and NPY-expressing cells: while the latter were lost at the injection site but preserved at intermediate sites, PV-expressing cells were gone even at sites more temporal than GCD. In addition, we found upregulation of GAD67 mRNA expression in dispersed granule cells and of NPY staining in ipsilateral granule cells and ipsi- and contralateral mossy fibers. Our data thus indicate differential survival capacity of interneurons in the epileptic hippocampus and compensatory plasticity mechanisms

  9. Traumatic brain injury upregulates phosphodiesterase expression in the hippocampus

    Directory of Open Access Journals (Sweden)

    Nicole M Wilson

    2016-02-01

    Full Text Available Traumatic brain injury (TBI results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3',5'-cyclic adenosine monophosphate (cAMP, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 hr and 6 hr after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6 and 24 hr after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 hr after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 hr after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b+ immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b+ immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of LTP into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive dysfunction acutely after TBI.

  10. The dynamics of adult neurogenesis in human hippocampus.

    Science.gov (United States)

    Ihunwo, Amadi O; Tembo, Lackson H; Dzamalala, Charles

    2016-12-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data.

  11. 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.

  12. Tau-positive grains are constant in centenarians' hippocampus.

    Science.gov (United States)

    Pham, Chi-Tuan; de Silva, Rohan; Haïk, Stéphane; Verny, Marc; Sachet, Annick; Forette, Bernard; Lees, Andrew; Hauw, Jean-Jacques; Duyckaerts, Charles

    2011-07-01

    The influence of age on the prevalence of argyrophilic grain disease has been analyzed in the hippocampus from 29 centenarians. Argyrophilic grains were detected in 12 cases with Gallyas silver method, in 24 cases with anti-exon 10 (RD4) immunohistochemistry, in all the cases with a phospho-independent anti-tau (piTau) antibody and with a monoclonal antibody against Ser202 of the tau protein (AT8), suggesting a maturation of the grains. Ballooned neurons were found in the hippocampus of 12 cases in which grains were, on average, more abundant. Coiled bodies were found in 26, 15 and 13 cases respectively with piTau antibody, RD4 and Gallyas method. Cases with coiled bodies had a higher density of grains. The mean density of grains did not differ in the patients with or without dementia. The prevalence of tau-positive grains has been underestimated in the very old population. As neurofibrillary tangles, they appear to be a constant accompaniment of age but, contrarily to neurofibrillary tangles, do not seem to be strongly associated with dementia.

  13. Proteomic Analysis of Rat Hippocampus under Simulated Microgravity

    Science.gov (United States)

    Wang, Yun; Li, Yujuan; Zhang, Yongqian; Liu, Yahui; Deng, Yulin

    It has been found that microgravity may lead to impairments in cognitive functions performed by CNS. However, the exact mechanism of effects of microgravity on the learning and memory function in animal nervous system is not elucidated yet. Brain function is mainly mediated by membrane proteins and their dysfunction causes degeneration of the learning and memory. To induce simulated microgravity, the rat tail suspension model was established. Comparative O (18) labeling quantitative proteomic strategy was applied to detect the differentially expressed proteins in rat brain hippocampus. The proteins in membrane fraction from rat hippocampus were digested by trypsin and then the peptides were separated by off-gel for the first dimension with 24 wells device encompassing the pH range of 3 - 10. An off-gel fraction was subjected into LC-ESI-QTOF in triplicate. Preliminary results showed that nearly 77% of the peptides identified were specific to one fraction. 676 proteins were identified among which 108 proteins were found differentially expressed under simulated microgravity. Using the KOBAS server, many enriched pathways, such as metabolic pathway, synaptic vesicle cycle, endocytosis, calcium signaling pathway, and SNAREs pathway were identified. Furthermore, it has been found that neurotransmitter released by Ca (2+) -triggered synaptic vesicles fusion may play key role in neural function. Rab 3A might inhibit the membrane fusion and neurotransmitter release. The protein alteration of the synaptic vesicle cycle may further explain the effects of microgravity on learning and memory function in rats. Key words: Microgravity; proteomics; synaptic vesicle; O (18) ({}) -labeling

  14. Anterior hippocampus and goal-directed spatial decision making.

    Science.gov (United States)

    Viard, Armelle; Doeller, Christian F; Hartley, Tom; Bird, Chris M; Burgess, Neil

    2011-03-23

    Planning spatial paths through our environment is an important part of everyday life and is supported by a neural system including the hippocampus and prefrontal cortex. Here we investigated the precise functional roles of the components of this system in humans by using fMRI as participants performed a simple goal-directed route-planning task. Participants had to choose the shorter of two routes to a goal in a visual scene that might contain a barrier blocking the most direct route, requiring a detour, or might be obscured by a curtain, requiring memory for the scene. The participant's start position was varied to parametrically manipulate their proximity to the goal and the difference in length of the two routes. Activity in medial prefrontal cortex, precuneus, and left posterior parietal cortex was associated with detour planning, regardless of difficulty, whereas activity in parahippocampal gyrus was associated with remembering the spatial layout of the visual scene. Activity in bilateral anterior hippocampal formation showed a strong increase the closer the start position was to the goal, together with medial prefrontal, medial and posterior parietal cortices. Our results are consistent with computational models in which goal proximity is used to guide subsequent navigation and with the association of anterior hippocampal areas with nonspatial functions such as arousal and reward expectancy. They illustrate how spatial and nonspatial functions combine within the anterior hippocampus, and how these functions interact with parahippocampal, parietal, and prefrontal areas in decision making and mnemonic function.

  15. Postictal single-cell firing patterns in the hippocampus.

    Science.gov (United States)

    Zhou, Jun-Li; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L

    2007-04-01

    Patients with epilepsy have varying degrees of postictal impairment including confusion and amnesia. This impairment adds substantially to the disease burden of epilepsy. However, the mechanism responsible for postictal cognitive impairment is unclear. The purpose of this study was to study single-cell firing patterns in hippocampal cells after spontaneous seizures in rats previously subjected to status epilepticus. In this study, we monitored place cells and interneurons in the CA1 region of the hippocampus before and after spontaneous seizures in six epileptic rats with a history of status epilepticus. Place cells fire action potentials when the animal is in a specific location in space, the so-called place field. Place cell function correlates well with performance in tasks of visual-spatial memory and appears to be an excellent surrogate measure of spatial memory. Twelve spontaneous seizures were recorded. After the seizures, a marked decrease in firing rate of action potentials from place cells was noted, whereas interneuron firing was unchanged. In addition, when place cell firing fields persisted or returned, they had aberrant firing fields with reduced coherence and information content. In addition to postictal suppression of firing patterns, seizures led to the emergence of firing fields in previously silent cells, demonstrating a postictal remapping of the hippocampus. These findings demonstrate that postictal alterations in behavior are not due solely to reduced neuronal firing. Rather, the postictal period is characterized by robust and dynamic changes in cell-firing patterns resulting in remapping of the hippocampal map.

  16. The hippocampus facilitates integration within a symbolic field.

    Science.gov (United States)

    Cornelius, John Thor

    2017-01-13

    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.

  17. Donor/Recipient Enhancement of Memory in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Sam A Deadwyler

    2013-12-01

    Full Text Available The critical role of the mammalian hippocampus in the formation, translation and retrieval of memory has been documented over many decades. There are many theories of how the hippocampus operates to encode events and a precise mechanism was recently identified in rats performing a short-term memory task which demonstrated that successful information encoding was promoted via specific patterns of activity generated within ensembles of hippocampal neurons. In the study presented here these ‘representations’ were extracted via a customized nonlinear multi-input multi-output (MIMO mathematical model which allowed prediction of successful performance on specific trials within the testing session. A unique feature of this characterization was demonstrated when successful information encoding patterns were derived online from well-trained donor animals during difficult long-delay trials and delivered via online electrical stimulation to synchronously tested naïve recipient animals never before exposed to the delay feature of the task. By transferring such model-derived trained (donor animal hippocampal firing patterns via stimulation to coupled naïve recipient animals, their task performance was facilitated in a direct donor-recipient manner. This provides the basis for utilizing extracted appropriate neural information from one brain to induce, recover, or enhance memory related processing in the brain of another subject.

  18. Repeated dose of ketamine effect to the rat hippocampus tissue

    Directory of Open Access Journals (Sweden)

    Mehtap Okyay Karaca

    2015-01-01

    Full Text Available Aim: We aimed to determine the neurotoxic effect of repeated ketamine administration on brain tissue and if neurotoxic effect was present, whether this effect continued 16 days later using histological stereological method, a quantitative and objective method. Materials and Methods: Female rats were divided into three groups, each containing five rats. Rats in Group I were given 0.9% saline solution 4 times a day for 5 days. The rats in Groups II and III were given ketamine as intraperitoneal injections. Rats in Groups I and II were sacrificed on 5 th day while the ones in Group III on 21 st day. Cornu ammonis (CA and gyrus dentatus (GD regions in hippocampus tissue of rats were studied using optic fractionation method. Findings: There were significantly less number of cells in hippocampal CA and GD regions of rats from Groups II and III compared to the ones from Group I. Difference in cell number was also significantly higher in Group III than in Group II, but this difference was not as pronounced as the one between Groups III and I. Conclusion: Repeated ketamine doses caused neurotoxicity in rat hippocampus.

  19. Neuromodulatory signaling in hippocampus-dependent memory retrieval.

    Science.gov (United States)

    Thomas, Steven A

    2015-04-01

    Considerable advances have been made toward understanding the molecular signaling events that underlie memory acquisition and consolidation. In contrast, less is known about memory retrieval, despite its necessity for utilizing learned information. This review focuses on neuromodulatory and intracellular signaling events that underlie memory retrieval mediated by the hippocampus, for which the most information is currently available. Among neuromodulators, adrenergic signaling is required for the retrieval of various types of hippocampus-dependent memory. Although they contribute to acquisition and/or consolidation, cholinergic and dopaminergic signaling are generally not required for retrieval. Interestingly, while not required for retrieval, serotonergic and opioid signaling may actually constrain memory retrieval. Roles for histamine and non-opioid neuropeptides are currently unclear but possible. A critical effector of adrenergic signaling in retrieval is reduction of the slow afterhyperpolarization mediated by β1 receptors, cyclic AMP, protein kinase A, Epac, and possibly ERK. In contrast, stress and glucocorticoids impair retrieval by decreasing cyclic AMP, mediated in part by the activation of β2 -adrenergic receptors. Clinically, alterations in neuromodulatory signaling and in memory retrieval occur in Alzheimer's disease, Down syndrome, depression, and post-traumatic stress disorder, and recent evidence has begun to link changes in neuromodulatory signaling with effects on memory retrieval.

  20. Role of Amygdala and Hippocampus in the Neural Circuit Subserving Conditioned Defeat in Syrian Hamsters

    Science.gov (United States)

    Markham, Chris M.; Taylor, Stacie L.; Huhman, Kim L.

    2010-01-01

    We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH…

  1. Post-training reversible inactivation of the hippocampus enhances novel object recognition memory

    NARCIS (Netherlands)

    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

  2. Recognition Memory and the Hippocampus: A Test of the Hippocampal Contribution to Recollection and Familiarity

    Science.gov (United States)

    Jeneson, Annette; Kirwan, C. Brock; Hopkins, Ramona O.; Wixted, John T.; Squire, Larry R.

    2010-01-01

    It has been suggested that the hippocampus selectively supports recollection and that adjacent cortex in the medial temporal lobe can support familiarity. Alternatively, it has been suggested that the hippocampus supports both recollection and familiarity. We tested these suggestions by assessing the performance of patients with hippocampal…

  3. 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…

  4. Effects of rhynchophylline on monoamine transmitters of striatum and hippocampus in cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    LUYuan-Fu; XIEXiao-Long; WUQin; WENGuo-Rong; YANGSu-Fen; SHIJing-Shan

    2004-01-01

    AIM To investigate the effects of rhynchophylline ( Rhy on monoamine transmitters and its metabolites in striatum and hippocampus of cerebral ischemic rats. METItODS The cerebral ischemic injury of rat was induced by middle cerebral artery occlusion (MCAO). The extracellular fluid of striatum and hippocampus in cerebral ischemic rats was collected by using

  5. 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,…

  6. Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam

    OpenAIRE

    Du, Yijuan; Grace, Anthony A.

    2016-01-01

    Background: Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats. Methods: We used an...

  7. Glucocorticoids modulate the response of ornithine decarboxylase to unilateral removal of the dorsal hippocampus

    NARCIS (Netherlands)

    De Kloet, E R; Cousin, M A; Veldhuis, H D; Voorhuis, T D; Lando, D

    1983-01-01

    The effect of unilateral removal of the dorsal hippocampus and of glucocorticoid administration was measured on the activity of ornithine decarboxylase (ODC) in the remaining contralateral hippocampus lobe. Unilateral hippocampectomy (Hx) resulted in a rapid rise of ODC activity in the contralateral

  8. Acetylcholine Release in the Hippocampus and Striatum during Place and Response Training

    Science.gov (United States)

    Pych, Jason C.; Chang, Qing; Colon-Rivera, Cynthia; Haag, Renee; Gold, Paul E.

    2005-01-01

    These experiments examined the release of acetylcholine in the hippocampus and striatum when rats were trained, within single sessions, on place or response versions of food-rewarded mazes. Microdialysis samples of extra-cellular fluid were collected from the hippocampus and striatum at 5-min increments before, during, and after training. These…

  9. 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…

  10. Role of Amygdala and Hippocampus in the Neural Circuit Subserving Conditioned Defeat in Syrian Hamsters

    Science.gov (United States)

    Markham, Chris M.; Taylor, Stacie L.; Huhman, Kim L.

    2010-01-01

    We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH…

  11. 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...

  12. Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3.

    Science.gov (United States)

    Perez-Alcazar, Marta; Daborg, Jonny; Stokowska, Anna; Wasling, Pontus; Björefeldt, Andreas; Kalm, Marie; Zetterberg, Henrik; Carlström, Karl E; Blomgren, Klas; Ekdahl, Christine T; Hanse, Eric; Pekna, Marcela

    2014-03-01

    Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured CNS. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.

  13. 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.

  14. [The effect of Solcoseryl on explant cultures of the hippocampus].

    Science.gov (United States)

    Lindner, G; Grosse, G; Goworek, K; Franz, C; Liebezeit, K

    1979-01-01

    Explants of hippocampus from fetal rats were cultivated in Maximow chambers in semisynthetic medium up to 12 days in vitro. The cultures were fixed Bouin, slided 15 micron, coloured with Klüver-Barrera and some morphological parameters were tested. 1. The nerve fiber index increased by influence of 1% Solcoseryl in relation to control cultures, which growed in minimal medium. An essential stimulation was observed by application of placentar serum and embryonal extract into the culture medium. 2. Die decrease of the number of neurons and glial cells per unit of area and a small decrease of the area of neuron nuclei was discussed in relation to the effect of the pharmacon Solcoseryl on O2- consumption. 3. Solcoseryl (firm Solco AG, Base) is an extract of calf blood. It can not substitute other tissue extracts.

  15. Synapse formation on neurons born in the adult hippocampus.

    Science.gov (United States)

    Toni, Nicolas; Teng, E Matthew; Bushong, Eric A; Aimone, James B; Zhao, Chunmei; Consiglio, Antonella; van Praag, Henriette; Martone, Maryann E; Ellisman, Mark H; Gage, Fred H

    2007-06-01

    Although new and functional neurons are produced in the adult brain, little is known about how they integrate into mature networks. Here we explored the mechanisms of synaptogenesis on neurons born in the adult mouse hippocampus using confocal microscopy, electron microscopy and live imaging. We report that new neurons, similar to mature granule neurons, were contacted by axosomatic, axodendritic and axospinous synapses. Consistent with their putative role in synaptogenesis, dendritic filopodia were more abundant during the early stages of maturation and, when analyzed in three dimensions, the tips of all filopodia were found within 200 nm of preexisting boutons that already synapsed on other neurons. Furthermore, dendritic spines primarily synapsed on multiple-synapse boutons, suggesting that initial contacts were preferentially made with preexisting boutons already involved in a synapse. The connectivity of new neurons continued to change until at least 2 months, long after the formation of the first dendritic protrusions.

  16. Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency.

    Science.gov (United States)

    Amilhon, Bénédicte; Huh, Carey Y L; Manseau, Frédéric; Ducharme, Guillaume; Nichol, Heather; Adamantidis, Antoine; Williams, Sylvain

    2015-06-03

    Hippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta.

  17. Chinese Traditional Medicine and Adult Neurogenesis in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Endong Zhang

    2014-04-01

    Full Text Available Adult neurogenesis is an important therapeutic target in treating neurological disorders. Adult neurogenesis takes place in two regions of the brain: Subventricular zone and dentate gyrus in the hippocampus. The progressive understanding on hippocampal neurogenesis in aging and mood disorders increases the demand to explore powerful and subtle interventions on hippocampal neurogenesis. Traditional Chinese herbal medicine provides an abundant pharmaceutical platform for modulating hippocampal neurogenesis. Recent progress in exploring the effects of Chinese herbal medicine and the related mechanisms opens a new direction for regeneration therapy. The current review gives a thorough summary of the research progress made in traditional Chinese herbal formulas, and the effective compounds in Chinese herbs which are beneficial on hippocampal neurogenesis and the possible mechanisms involved.

  18. A Critical Role for the Hippocampus in the Valuation of Imagined Outcomes

    Science.gov (United States)

    Lebreton, Maël; Bertoux, Maxime; Boutet, Claire; Lehericy, Stéphane; Dubois, Bruno; Fossati, Philippe; Pessiglione, Mathias

    2013-01-01

    Many choice situations require imagining potential outcomes, a capacity that was shown to involve memory brain regions such as the hippocampus. We reasoned that the quality of hippocampus-mediated simulation might therefore condition the subjective value assigned to imagined outcomes. We developed a novel paradigm to assess the impact of hippocampus structure and function on the propensity to favor imagined outcomes in the context of intertemporal choices. The ecological condition opposed immediate options presented as pictures (hence directly observable) to delayed options presented as texts (hence requiring mental stimulation). To avoid confounding simulation process with delay discounting, we compared this ecological condition to control conditions using the same temporal labels while keeping constant the presentation mode. Behavioral data showed that participants who imagined future options with greater details rated them as more likeable. Functional MRI data confirmed that hippocampus activity could account for subjects assigning higher values to simulated options. Structural MRI data suggested that grey matter density was a significant predictor of hippocampus activation, and therefore of the propensity to favor simulated options. Conversely, patients with hippocampus atrophy due to Alzheimer's disease, but not patients with Fronto-Temporal Dementia, were less inclined to favor options that required mental simulation. We conclude that hippocampus-mediated simulation plays a critical role in providing the motivation to pursue goals that are not present to our senses. PMID:24167442

  19. Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory.

    Science.gov (United States)

    Kempadoo, Kimberly A; Mosharov, Eugene V; Choi, Se Joon; Sulzer, David; Kandel, Eric R

    2016-12-20

    Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.

  20. Neuronal nitric oxide synthase is an endogenous negative regulator of glucocorticoid receptor in the hippocampus.

    Science.gov (United States)

    Liu, Meng-ying; Zhu, Li-Juan; Zhou, Qi-Gang

    2013-07-01

    The hippocampus is rich in both glucocorticoid receptor (GR) and neuronal nitric oxide synthase (nNOS). But the relationship between the two molecules under physiological states remains unrevealed. Here, we report that nNOS knockout mice display increased GR expression in the hippocampus. Both systemic administration of 7-Nitroindazole (7-NI), a selective nNOS activity inhibitor, and selective infusion of 7-NI into the hippocampus resulted in an increase in GR expression in the hippocampus. Moreover, KCl exposure, which can induce overexpression of nNOS, resulted in a decrease in GR protein level in cultured hippocampal neurons. Moreover, blockade of nNOS activity in the hippocampus leads to decreased corticosterone (CORT, glucocorticoids in rodents) concentration in the plasma and reduced corticotrophin-releasing factor expression in the hypothalamus. The results indicate that nNOS is an endogenous inhibitor of GR in the hippocampus and that nNOS in the hippocampus may participate in the modulation of Hypothalamic-Pituitary-Adrenal axis activity via GR.

  1. 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 GABAA 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.

  2. Organization and chemical neuroanatomy of the African elephant (Loxodonta africana) hippocampus.

    Science.gov (United States)

    Patzke, Nina; Olaleye, Olatunbosun; Haagensen, Mark; Hof, Patrick R; Ihunwo, Amadi O; Manger, Paul R

    2014-09-01

    Elephants are thought to possess excellent long-term spatial-temporal and social memory, both memory types being at least in part hippocampus dependent. Although the hippocampus has been extensively studied in common laboratory mammalian species and humans, much less is known about comparative hippocampal neuroanatomy, and specifically that of the elephant. Moreover, the data available regarding hippocampal size of the elephant are inconsistent. The aim of the current study was to re-examine hippocampal size and provide a detailed neuroanatomical description of the hippocampus in the African elephant. In order to examine the hippocampal size the perfusion-fixed brains of three wild-caught adult male African elephants, aged 20-30 years, underwent MRI scanning. For the neuroanatomical description brain sections containing the hippocampus were stained for Nissl, myelin, calbindin, calretinin, parvalbumin and doublecortin. This study demonstrates that the elephant hippocampus is not unduly enlarged, nor specifically unusual in its internal morphology. The elephant hippocampus has a volume of 10.84 ± 0.33 cm³ and is slightly larger than the human hippocampus (10.23 cm(3)). Histological analysis revealed the typical trilaminated architecture of the dentate gyrus (DG) and the cornu ammonis (CA), although the molecular layer of the dentate gyrus appears to have supernumerary sublaminae compared to other mammals. The three main architectonic fields of the cornu ammonis (CA1, CA2, and CA3) could be clearly distinguished. Doublecortin immunostaining revealed the presence of adult neurogenesis in the elephant hippocampus. Thus, the elephant exhibits, for the most part, what might be considered a typically mammalian hippocampus in terms of both size and architecture.

  3. 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

    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...... index, 0.87, and correlation coefficient, 0.94, with semi-automatically generated segmentations. When comparing hippocampus volumes extracted from 1.5T and 3T images, the absolute value of the difference was low: 3.2% of the volume. The correct classification rate for Alzheimer's disease and cognitively...

  4. Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE

    DEFF Research Database (Denmark)

    Valen, Eivind; Pascarella, Giovanni; Chalk, Alistair;

    2009-01-01

    in a given tissue. Here, we present a new method for high-throughput sequencing of 5' cDNA tags-DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth...... of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for the Arnt2 transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters...

  5. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring...... of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  6. Midazolam inhibits neophobia-induced Fos expression in the rat hippocampus.

    Science.gov (United States)

    Wisłowska-Stanek, A; Zienowicz, M; Lehner, M; Taracha, E; Bidziński, A; Maciejak, P; Skórzewska, A; Szyndler, J; Płaźnik, A

    2006-01-01

    The effect of midazolam on expression of c-Fos protein was examined in the rat hippocampus, following the open field test of neophobia. It was found that pretreatment of rats with midazolam, at the dose of 0.5 mg/kg, enhanced rat exploratory behavior, and inhibited neophobia related stimulation of c-Fos in the CA-1 and CA-3 areas of the hippocampus. The presented results provide new immunocytochemical data on the involvement of hippocampus in emotional processes related to neophobia, and indicate a possible site of action of benzodiazepines.

  7. 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

  8. Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

    Science.gov (United States)

    Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

  9. DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

    Science.gov (United States)

    Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

  10. Neurotransmitter evaluation in the hippocampus of rats after intracerebral injection of TsTX scorpion toxin

    Directory of Open Access Journals (Sweden)

    ALA Nencioni

    2009-01-01

    Full Text Available TsTX is an α-type sodium channel toxin that stimulates the discharge of neurotransmitters from neurons. In the present study we investigated which neurotransmitters are released in the hippocampus after TsTX injection and if they are responsible for electrographic or histopathological effects. Microdialysis revealed that the toxin increased glutamate extracellular levels in the hippocampus; however, levels of gamma-aminobutyric acid (GABA, glycine, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC were not significantly altered. Neurodegeneration in pyramidal cells of hippocampus and electroencephalographic alterations caused by the toxin were blocked by pretreatment with riluzole, a glutamate release inhibitor. The present results suggest a specific activity of TsTX in the hippocampus which affects only glutamate release.

  11. Extensive learning is associated with gray matter changes in the right hippocampus.

    Science.gov (United States)

    Koch, Kathrin; Reess, Tim Jonas; Rus, Oana Georgiana; Zimmer, Claus

    2016-01-15

    Longitudinal voxel-based morphometry studies have demonstrated increases in gray matter volume in hippocampal areas following extensive cognitive learning. Moreover, there is increasing evidence for the relevance of the subiculum in the context of learning and memory. Using longitudinal FreeSurfer analyses and hippocampus subfield segmentation the present study investigated the effects of 14weeks of intensive learning on hippocampal and subicular gray matter volume in a sample of medical students compared to control subjects not engaged in any cognitive learning activities. We found that extensive learning resulted in a significant increase of right hippocampal volume. Volume of the left hippocampus and the subiculum remained unchanged. The current findings emphasize the role of the hippocampus in semantic learning and memory processes and provide further evidence for the neuroplastic ability of the hippocampus in the context of cognitive learning.

  12. Epileptogenic actions of GABA and fast oscillations in the developing hippocampus.

    Science.gov (United States)

    Khalilov, Ilgam; Le Van Quyen, Michel; Gozlan, Henri; Ben-Ari, Yehezkel

    2005-12-08

    GABA excites immature neurons and inhibits adult ones, but whether this contributes to seizures in the developing brain is not known. We now report that in the developing, but not the adult, hippocampus, seizures beget seizures only if GABAergic synapses are functional. In the immature hippocampus, seizures generated with functional GABAergic synapses include fast oscillations that are required to transform a naive network to an epileptic one: blocking GABA receptors prevents the long-lasting sequels of seizures. In contrast, in adult neurons, full blockade of GABA(A) receptors generates epileptogenic high-frequency seizures. Therefore, purely glutamatergic seizures are not epileptogenic in the developing hippocampus. We suggest that the density of glutamatergic synapses is not sufficient for epileptogenesis in immature neurons; excitatory GABAergic synapses are required for that purpose. We suggest that the synergistic actions of GABA and NMDA receptors trigger the cascades involved in epileptogenesis in the developing hippocampus.

  13. Volumetric MRI Analysis of the Amygdala and Hippocampus in Subjects with Major Depression

    Institute of Scientific and Technical Information of China (English)

    夏军; 陈军; 周义成; 张景峰; 杨波; 夏黎明; 王承缘

    2004-01-01

    In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared with 13 age-matched controls. The results showed that both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the major depression group than that in control group. The patients had significant asymmetry of the amygdalar volumes (right smaller than left). No correlation was found between hippocampal volume abnormalities and ill duration. It was concluded that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.

  14. Ethanol neurobehavioural teratogenesis and the role of L-glutamate in the fetal hippocampus.

    Science.gov (United States)

    Reynolds, J D; Brien, J F

    1995-09-01

    The purpose of this article is to review the current state of knowledge of ethanol neurobehavioural teratogenesis and its postulated mechanisms. The review comprises an examination of ethanol teratogenesis in the human, including the fetal alcohol syndrome, and in experimental animals. Several current proposed mechanisms of ethanol neurobehavioural teratogenesis are critically assessed, including the role of acetaldehyde as the proximate metabolite of ethanol; fetal hypoxia; placental dysfunction; fetal prostaglandin metabolism; and action of ethanol on developing neurons in the fetal brain, including the hippocampus, one of ethanol's main target sites. The effect of ethanol on the release of L-glutamate, an excitatory amino acid neurotransmitter, in the fetal hippocampus is described, and the role of L-glutamate in ethanol teratogenesis involving the hippocampus is discussed. A novel mechanism for abnormal neuronal development in the fetal hippocampus produced by prenatal ethanol exposure is presented, and future experiments to test this hypothesis are proposed.

  15. 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.

  16. The tired hippocampus : The molecular impact of sleep deprivation on hippocampal function

    NARCIS (Netherlands)

    Havekes, Robbert; Abel, Ted

    2017-01-01

    Memory consolidation, the process by which information is stored following training, consists of synaptic consolidation and systems consolidation. It is widely acknowledged that sleep deprivation has a profound effect on synaptic consolidation, particularly for memories that require the hippocampus.

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  18. 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.

  19. Feature selective temporal prediction of Alzheimer's disease progression using hippocampus surface morphometry

    National Research Council Canada - National Science Library

    Tsao, Sinchai; Gajawelli, Niharika; Zhou, Jiayu; Shi, Jie; Ye, Jieping; Wang, Yalin; Leporé, Natasha

    2017-01-01

    In this work, we present our results of using machine learning to predict temporal behavior changes in Alzheimers Disease using entire topological feature maps of the hippocampus surface (2100 feature points...

  20. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep

    NARCIS (Netherlands)

    Staresina, B.P.; Bergmann, T.O.; Bonnefond, M.; Meij, R. van der; Jensen, O.; Deuker, L.; Elger, C.E.; Axmacher, N.; Fell, J.

    2015-01-01

    During systems-level consolidation, mnemonic representations initially reliant on the hippocampus are thought to migrate to neocortical sites for more permanent storage, with an eminent role of sleep for facilitating this information transfer. Mechanistically, consolidation processes have been hypot

  1. Modulation of Hippocampus-Dependent Learning and Synaptic Plasticity by Nicotine

    OpenAIRE

    Kenney, Justin W.; Gould, Thomas J.

    2008-01-01

    A long-standing relationship between nicotinic acetylcholine receptors (nAChRs) and cognition exists. Drugs that act at nAChRs can have cognitive-enhancing effects and diseases that disrupt cognition such as Alzheimer’s disease and schizophrenia are associated with altered nAChR function. Specifically, hippocampus-dependent learning is particularly sensitive to the effects of nicotine. However, the effects of nicotine on hippocampus-dependent learning vary not only with the doses of nicotine ...

  2. Free Radicals Mediate Peroxidative Damage in Guinea Pig Hippocampus in vitro

    Science.gov (United States)

    1989-01-01

    brane proteins . Protein oxidizing agents, chloramine -T the hydroxyl radicals at one site while at another site, the and n-chlorosuccinimide, produced only... proteins are also in MDA without causing any direct effects (Table I). likely to be present in the tissue: hemoglobin and trans- DMSO also... proteins can, under certain conditions, release Free Radical Damage in Hippocampus 443 TABLE I. Effect of Protectants on Malonaldehyde Levels in Hippocampus

  3. Interactions between the Lateral Habenula and the Hippocampus: Implication for Spatial Memory Processes

    OpenAIRE

    Goutagny, Romain; Loureiro, Michael; Jackson, Jesse; Chaumont, Joseph; Williams, Sylvain; Isope, Philippe; Kelche, Christian; Cassel, Jean-Christophe; Lecourtier, Lucas

    2013-01-01

    The lateral habenula (LHb) is an epithalamic structure connected with both the basal ganglia and the limbic system and that exerts a major influence on midbrain monoaminergic nuclei. The current view is that LHb receives and processes cortical information in order to select proper strategies in a variety of behavior. Recent evidence indicates that LHb might also be implicated in hippocampus-dependent memory processes. However, if and how LHb functionally interacts with the dorsal hippocampus ...

  4. Effects of motilin in the hippocampus on the interdigestive migrating motor complex in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Mei; DONG Lei; DUAN Zhong-ping; ZHU Wen-yi; CUI Yang; LEI Li

    2005-01-01

    Objective :To explore the effects of motilin in the hippocampus on the interdigestive migrating motor complex (MMC) in rats. Methods: Adult SD rats of either sex were used; 0.5 μl motilin (0. 74mmol/L) was injected into the guide cannula which was stereotaxically implanted into the hippocampus previously. Then the MMC was recorded by a RM6240B multilead physiological recording system. Results: (1) MMC characteristics of normal rats' duodenum: the frequency of phase Ⅲ was (18. 1 ± 0. 4)bursts/min; the amplitude of phase Ⅲ was (260. 5±42.3)μV; the duration of phase Ⅲ was (354. 1±21.6) s; MMC cycle duration was (690.2±58.7)s. (2) After motilin was injected into the hippocampus,the duodenal MMC cycle duration was decreased significantly. However, the amplitude of phase Ⅲ and the frequency of phase Ⅲ were increased. But there were no effects on the duration of phase Ⅲ. Frequency of phase Ⅲ percentage change was much more than amplitude of phase Ⅲ percentage change (57.2±2.8 vs39.3± 5. 2). (3) Effects of motilin in the hippocampus on MMC were completely abolished by subdiaphragmal vagotomy. (4) Effects of motilin in the hippocampus on MMC were unaffected by intravenously injected atropine, phentolamine or propranolol. (5) The anti-motilin serum partly abolished the effects of motilin in the hippocampus on MMC. Conclusion: Motilin in the hippocampus has effects on the duodenal MMC cycle duration, the amplitude of phase Ⅲ and the frequency of phase Ⅲ. Motilin in the hippocampus plays an important role in duodenal MMC.

  5. Environmental Enrichment Modifies the PKA-Dependence of Hippocampal LTP and Improves Hippocampus-Dependent Memory

    OpenAIRE

    Duffy, Steven N.; Craddock, Kenneth J.; Abel, Ted; Nguyen, Peter V.

    2001-01-01

    cAMP-dependent protein kinase (PKA) is critical for the expression of some forms of long-term potentiation (LTP) in area CA1 of the mouse hippocampus and for hippocampus-dependent memory. Exposure to spatially enriched environments can modify LTP and improve behavioral memory in rodents, but the molecular bases for the enhanced memory performance seen in enriched animals are undefined. We tested the hypothesis that exposure to a spatially enriched environment may alter the PKA dependence of h...

  6. Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning

    OpenAIRE

    Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Rezayof, Ameneh; Darbandi, Niloufar

    2015-01-01

    Morphine’s effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance t...

  7. Interactions between the Lateral Habenula and the Hippocampus: Implication for Spatial Memory Processes

    OpenAIRE

    Goutagny, Romain; Loureiro, Michael; Jackson, Jesse; Chaumont, Joseph; Williams, Sylvain; Isope, Philippe; Kelche, Christian; Cassel, Jean-Christophe; Lecourtier, Lucas

    2013-01-01

    The lateral habenula (LHb) is an epithalamic structure connected with both the basal ganglia and the limbic system and that exerts a major influence on midbrain monoaminergic nuclei. The current view is that LHb receives and processes cortical information in order to select proper strategies in a variety of behavior. Recent evidence indicates that LHb might also be implicated in hippocampus-dependent memory processes. However, if and how LHb functionally interacts with the dorsal hippocampus ...

  8. [What's new in the hippocampus? Neurons regenerate in the adult brain].

    Science.gov (United States)

    Sela, B A

    2001-11-01

    Since the late 1960's, the production of new neurons was known to occur in the brains of adult rodents however, only recently, neurogenesis was documented in the hippocampus of adult mammals. This region in the brain is related to the function of learning and memory. Hence, the finding that in response to training on associative learning tasks that require the hippocampus the number of newly generated neurons increases, could be highly significant.

  9. 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.

  10. Effect of maternal diabetes on gliogensis in neonatal rat hippocampus

    Science.gov (United States)

    Sadeghi, Akram; Esfandiary, Ebrahim; Hami, Javad; Khanahmad, Hossein; Hejazi, Zahra; Razavi, Shahnaz

    2016-01-01

    Background: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). Materials and Methods: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. Results: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P 0.05). Conclusion: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus. PMID:27656611

  11. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    Science.gov (United States)

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  12. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

    Directory of Open Access Journals (Sweden)

    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.

  13. Modulation of adult-born neurons in the inflamed hippocampus

    Directory of Open Access Journals (Sweden)

    Karim eBelarbi

    2013-09-01

    Full Text Available Throughout life new neurons are continuously added to the hippocampal circuitry involved with spatial learning and memory. These new cells originate from neural precursors in the subgranular zone of the dentate gyrus, migrate into the granule cell layer and integrate into neural networks encoding spatial and contextual information. This process can be influenced by several environmental and endogenous factors and is modified in different animal models of neurological disorders. Neuroinflammation, as defined by the presence of activated microglia, is a common key factor to the progression of neurological disorders. Analysis of the literature shows that microglial activation impacts not only the production, but also the migration and the recruitment of new neurons. The impact of microglia on adult-born neurons appears much more multifaceted than ever envisioned before, combining both supportive and detrimental effects that are dependent upon the activation phenotype and the factors being released. The development of strategies aimed to change microglia toward states that promote functional neurogenesis could therefore offer novel therapeutic opportunities against neurological disorders associated with cognitive deficits and neuroinflammation. The present review summarizes the current knowledge on how production, distribution and recruitment of new neurons into behaviorally relevant neural networks are modified in the inflamed hippocampus.

  14. Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus.

    Science.gov (United States)

    Chetty, Sundari; Friedman, Aaron R; Taravosh-Lahn, Kereshmeh; Kirby, Elizabeth D; Mirescu, Christian; Guo, Fuzheng; Krupik, Danna; Nicholas, Andrea; Geraghty, Anna; Krishnamurthy, Amrita; Tsai, Meng-Ko; Covarrubias, David; Wong, Alana; Francis, Darlene; Sapolsky, Robert M; Palmer, Theo D; Pleasure, David; Kaufer, Daniela

    2014-12-01

    Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.

  15. Neural representation of spatial topology in the rodent hippocampus.

    Science.gov (United States)

    Chen, Zhe; Gomperts, Stephen N; Yamamoto, Jun; Wilson, Matthew A

    2014-01-01

    Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning in navigation. Although it has been long suggested that pyramidal cell activity may underlie a topological code rather than a topographic code, it remains unclear whether an abstract spatial topology can be encoded in the ensemble spiking activity of hippocampal place cells. Using a statistical approach developed previously, we investigate this question and related issues in greater detail. We recorded ensembles of hippocampal neurons as rodents freely foraged in one- and two-dimensional spatial environments and used a "decode-to-uncover" strategy to examine the temporally structured patterns embedded in the ensemble spiking activity in the absence of observed spatial correlates during periods of rodent navigation or awake immobility. Specifically, the spatial environment was represented by a finite discrete state space. Trajectories across spatial locations ("states") were associated with consistent hippocampal ensemble spiking patterns, which were characterized by a state transition matrix. From this state transition matrix, we inferred a topology graph that defined the connectivity in the state space. In both one- and two-dimensional environments, the extracted behavior patterns from the rodent hippocampal population codes were compared against randomly shuffled spike data. In contrast to a topographic code, our results support the efficiency of topological coding in the presence of sparse sample size and fuzzy space mapping. This computational approach allows us to quantify the variability of ensemble spiking activity, examine hippocampal population codes during off-line states, and quantify the topological complexity of the environment.

  16. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  17. Automated segmentation of the human hippocampus along its longitudinal axis.

    Science.gov (United States)

    Lerma-Usabiaga, Garikoitz; Iglesias, Juan Eugenio; Insausti, Ricardo; Greve, Douglas N; Paz-Alonso, Pedro M

    2016-09-01

    The human hippocampal formation is a crucial brain structure for memory and cognitive function that is closely related to other subcortical and cortical brain regions. Recent neuroimaging studies have revealed differences along the hippocampal longitudinal axis in terms of structure, connectivity, and function, stressing the importance of improving the reliability of the available segmentation methods that are typically used to divide the hippocampus into its anterior and posterior parts. However, current segmentation conventions present two main sources of variability related to manual operations intended to correct in-scanner head position across subjects and the selection of dividing planes along the longitudinal axis. Here, our aim was twofold: (1) to characterize inter- and intra-rater variability associated with these manual operations and compare manual (landmark based) and automatic (percentage based) hippocampal anterior-posterior segmentation procedures; and (2) to propose and test automated rotation methods based on approximating the hippocampal longitudinal axis to a straight line (estimated with principal component analysis, PCA) or a quadratic Bézier curve (fitted with numerical methods); as well as an automated anterior-posterior hippocampal segmentation procedure based on the percentage-based method. Our results reveal that automated rotation and segmentation procedures, used in combination or independently, minimize inconsistencies generated by the accumulation of manual operations while providing higher statistical power to detect well-known effects. A Matlab-based implementation of these procedures is made publicly available to the research community. Hum Brain Mapp 37:3353-3367, 2016. © 2016 Wiley Periodicals, Inc.

  18. Building models for postmortem abnormalities in hippocampus of schizophrenics.

    Science.gov (United States)

    Benes, Francine M

    2015-09-01

    Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics.

  19. 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.

  20. What Representations and Computations Underpin the Contribution of the Hippocampus to Generalization and Inference?

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    Dharshan eKumaran

    2012-06-01

    Full Text Available Empirical research and theoretical accounts have traditionally emphasized the function of the hippocampus in episodic memory. Here we draw attention to the importance of the hippocampus to generalization, and focus on the neural representations and computations that might underpin its role in tasks such as the paired associate inference paradigm. We make a principal distinction between two different mechanisms by which the hippocampus may support generalization: an encoding-based mechanism that creates overlapping representations that capture higher-order relationships between different items (e.g. TCM – and a retrieval-based model (REMERGE that effectively computes these relationships at the point of retrieval, through a recurrent mechanism that allows the dynamic interaction of multiple pattern separated episodic codes. We also discuss what we refer to as transfer effects - a more abstract example of generalization that has also been linked to the function of the hippocampus. We consider how this phenomenon poses inherent challenges for models such as TCM and REMERGE, and outline the potential applicability of a separate class of models - hierarchical bayesian models (HBMs in this context. Our hope is that this article will provide a basic framework within which to consider the theoretical mechanisms underlying the role of the hippocampus in generalization, and at a minimum serve as a stimulus for future work addressing issues that go to the heart of the function of the hippocampus.

  1. An unexpected sequence of events: mismatch detection in the human hippocampus.

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    Dharshan Kumaran

    2006-11-01

    Full Text Available The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus, therefore, is viewed to detect associative mismatches between what is expected based on retrieval of past experience and current sensory input. However, direct evidence that the human hippocampus performs such operations is lacking. We explored brain responses to novel sequences of objects using functional magnetic resonance imaging (fMRI, while subjects performed an incidental target detection task. Our results demonstrate that hippocampal activation was maximal when prior predictions concerning which object would appear next in a sequence were violated by sensory reality. In so doing, we establish the biological reality of associative match-mismatch computations within the human hippocampus, a process widely held to play a cardinal role in novelty detection. Our results also suggest that the hippocampus may generate predictions about how future events will unfold, and critically detect when these expectancies are violated, even when task demands do not require it. The present study also offers broader insights into the nature of essential computations carried out by the hippocampus, which may also underpin its unique contribution to episodic memory.

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

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    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.

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

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    Carmen Varela

    Full Text Available 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.

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

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    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.

  5. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories

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    Brittany M. Jeye

    2017-01-01

    Full Text Available False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the “left” or “right” visual field followed by an “unsure”–“sure”–“very sure” confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right–“left”–“very sure” responses from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories.

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

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

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    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.

  8. Neuroprotection by urokinase plasminogen activator in the hippocampus.

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    Cho, Eunsil; Lee, Kyung Jin; Seo, Jung-Woo; Byun, Catherine Jeonghae; Chung, Sun-Ju; Suh, Dae Chul; Carmeliet, Peter; Koh, Jae-Young; Kim, Jong S; Lee, Joo-Yong

    2012-04-01

    Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are both used for thrombolytic treatment of acute ischemic stroke, are serine proteases that convert plasminogen to active plasmin. Although recent experimental evidences have raised controversy about the neurotoxic versus neuroprotective roles of tPA in acute brain injury, uPA remains unexplored in this context. In this study, we evaluated the effect of uPA on neuronal death in the hippocampus of mice after kainate-induced seizures. In the normal brain, uPA was localized to both nuclei and cytosol of neurons. Following severe kainate-induced seizures, uPA completely disappeared in degenerating neurons, whereas uPA-expressing astrocytes substantially increased, suggesting reactive astrogliosis. uPA-knockout mice were more vulnerable to kainate-induced neuronal death than wild-type mice. Consistent with this, inhibition of uPA by intracerebral injection of the uPA inhibitor UK122 increased the level of neuronal death. In contrast, prior administration of recombinant uPA significantly attenuated neuronal death. Collectively, these results indicate that uPA renders neurons resistant to kainate-induced excitotoxicity. Moreover, recombinant uPA suppressed cell death in primary cultures of hippocampal neurons exposed to H2O2, zinc, or various excitotoxins, suggesting that uPA protects against neuronal injuries mediated by the glutamate receptor, or by oxidation- or zinc-induced death signaling pathways. Considering that tPA may facilitate neurodegeneration in acute brain injury, we suggest that uPA, as a neuroprotectant, might be beneficial for the treatment of acute brain injuries such as ischemic stroke.

  9. Theta coordinated error-driven learning in the hippocampus.

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    Nicholas Ketz

    Full Text Available The learning mechanism in the hippocampus has almost universally been assumed to be Hebbian in nature, where individual neurons in an engram join together with synaptic weight increases to support facilitated recall of memories later. However, it is also widely known that Hebbian learning mechanisms impose significant capacity constraints, and are generally less computationally powerful than learning mechanisms that take advantage of error signals. We show that the differential phase relationships of hippocampal subfields within the overall theta rhythm enable a powerful form of error-driven learning, which results in significantly greater capacity, as shown in computer simulations. In one phase of the theta cycle, the bidirectional connectivity between CA1 and entorhinal cortex can be trained in an error-driven fashion to learn to effectively encode the cortical inputs in a compact and sparse form over CA1. In a subsequent portion of the theta cycle, the system attempts to recall an existing memory, via the pathway from entorhinal cortex to CA3 and CA1. Finally the full theta cycle completes when a strong target encoding representation of the current input is imposed onto the CA1 via direct projections from entorhinal cortex. The difference between this target encoding and the attempted recall of the same representation on CA1 constitutes an error signal that can drive the learning of CA3 to CA1 synapses. This CA3 to CA1 pathway is critical for enabling full reinstatement of recalled hippocampal memories out in cortex. Taken together, these new learning dynamics enable a much more robust, high-capacity model of hippocampal learning than was available previously under the classical Hebbian model.

  10. Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.

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    Stern, Shani; Agudelo-Toro, Andres; Rotem, Assaf; Moses, Elisha; Neef, Andreas

    2015-01-01

    Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields.

  11. Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.

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    Shani Stern

    Full Text Available Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields.

  12. Imipramine protects mouse hippocampus against tunicamycin-induced cell death.

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    Ono, Yoko; Shimazawa, Masamitsu; Ishisaka, Mitsue; Oyagi, Atsushi; Tsuruma, Kazuhiro; Hara, Hideaki

    2012-12-05

    Endoplasmic reticulum (ER) stress is implicated in various diseases. Recently, some reports have suggested that the sigma-1 receptor may play a role in ER stress, and many antidepressants have a high affinity for the sigma-1 receptor. In the present study, we focused on imipramine, a widely used antidepressant, and investigated whether it might protect against the neuronal cell death induced by tunicamycin, an ER stress inducer. In mouse cultured hippocampal HT22 cells, imipramine inhibited cell death and caspase-3 activation induced by tunicamycin, although it did not alter the elevated expressions of 78 kDa glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP). Interestingly, in such cells application of imipramine normalized the expression of the sigma-1 receptor, which was decreased by treatment with tunicamycin alone. Additionally, NE-100, a selective sigma-1 receptor antagonist, abolished the protective effect of imipramine against such tunicamycin-induced cell death. Imipramine inhibited the reduction of mitochondrial membrane potential induced by tunicamycin, and NE-100 blocked this modulating effect of imipramine. Furthermore, in anesthetized mice intracerebroventricular administration of tunicamycin decreased the number of neuronal cells in the hippocampus, particularly in the CA1 and dentate gyrus (DG) areas, and 7 days' imipramine treatment (10mg/kg/day; i.p.) significantly suppressed these reductions in CA1 and DG. These findings suggest that imipramine protects against ER stress-induced hippocampal neuronal cell death both in vitro and in vivo. Such protection may be partly due to the sigma-1 receptor.

  13. Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus

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    Mattei, Vincenzo; Martellucci, Stefano; Santilli, Francesca; Manganelli, Valeria; Garofalo, Tina; Candelise, Niccolò; Caruso, Alessandra; Sorice, Maurizio; Scaccianoce, Sergio

    2017-01-01

    The hippocampus is a vulnerable brain structure susceptible to damage during aging and chronic stress. Repeated exposure to opioids may alter the brain so that it functions normally when the drugs are present, thus, a prolonged withdrawal might lead to homeostatic changes headed for the restoration of the physiological state. Abuse of morphine may lead to Reacting Oxygen Species-induced neurodegeneration and apoptosis. It has been proposed that during morphine withdrawal, stress responses might be responsible, at least in part, for long-term changes of hippocampal plasticity. Since prion protein is involved in both, Reacting Oxygen Species mediated stress responses and synaptic plasticity, in this work we investigate the effect of opiate withdrawal in rats after morphine treatment. We hypothesize that stressful stimuli induced by opiate withdrawal, and the subsequent long-term homeostatic changes in hippocampal plasticity, might modulate the Prion protein expression. Our results indicate that abstinence from the opiate induced a time-dependent and region-specific modification in Prion protein content, indeed during morphine withdrawal a selective unbalance of hippocampal Prion Protein is observable. Moreover, Prion protein overexpression in hippocampal tissue seems to generate a dimeric structure of Prion protein and α-cleavage at the hydrophobic domain. Stress factors or toxic insults can induce cytosolic dimerization of Prion Protein through the hydrophobic domain, which in turn, it stimulates the α-cleavage and the production of neuroprotective Prion protein fragments. We speculate that this might be the mechanism by which stressful stimuli induced by opiate withdrawal and the subsequent long-term homeostatic changes in hippocampal plasticity, modulate the expression and the dynamics of Prion protein. PMID:28081197

  14. A key role for nectin-1 in the ventral hippocampus in contextual fear memory.

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    Fantin, Martina; van der Kooij, Michael A; Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen

    2013-01-01

    Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1-but not nectin-3-protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal

  15. Structural layers of ex vivo rat hippocampus at 7T MRI.

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    Jeanine Manuella Kamsu

    Full Text Available Magnetic resonance imaging (MRI applied to the hippocampus is challenging in studies of the neurophysiology of memory and the physiopathology of numerous diseases such as epilepsy, Alzheimer's disease, ischemia, and depression. The hippocampus is a well-delineated cerebral structure with a multi-layered organization. Imaging of hippocampus layers is limited to a few studies and requires high magnetic field and gradient strength. We performed one conventional MRI sequence on a 7T MRI in order to visualize and to delineate the multi-layered hippocampal structure ex vivo in rat brains. We optimized a volumic three-dimensional T2 Rapid Acquisition Relaxation Enhancement (RARE sequence and quantified the volume of the hippocampus and one of its thinnest layers, the stratum granulare of the dentate gyrus. Additionally, we tested passive staining by gadolinium with the aim of decreasing the acquisition time and increasing image contrast. Using appropriated settings, six discrete layers were differentiated within the hippocampus in rats. In the hippocampus proper or Ammon's Horn (AH: the stratum oriens, the stratum pyramidale of, the stratum radiatum, and the stratum lacunosum moleculare of the CA1 were differentiated. In the dentate gyrus: the stratum moleculare and the stratum granulare layer were seen distinctly. Passive staining of one brain with gadolinium decreased the acquisition time by four and improved the differentiation between the layers. A conventional sequence optimized on a 7T MRI with a standard receiver surface coil will allow us to study structural layers (signal and volume of hippocampus in various rat models of neuropathology (anxiety, epilepsia, neurodegeneration.

  16. A key role for nectin-1 in the ventral hippocampus in contextual fear memory.

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    Martina Fantin

    Full Text Available Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1-but not nectin-3-protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the

  17. Nicotine induction of theta frequency oscillations in rodent hippocampus in vitro.

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    Lu, C B; Henderson, Z

    2010-03-10

    The hippocampus is an area important for learning and memory and exhibits prominent and behaviourally relevant theta (4-12 Hz) and gamma (30-100 Hz) frequency oscillations in vivo. Hippocampal slices produce similar types of oscillatory activity in response to bath-application of neurotransmitter receptor agonists. The medial septum diagonal band area (MS/DB) provides both a cholinergic and GABAergic projection to the hippocampus, and although it plays a major role in the generation and maintenance of the hippocampal theta rhythm in vivo, there is evidence for intrinsic theta generation mechanisms in the hippocampus, especially in area CA3. The aim of this study was to examine the role of the nicotinic receptor (nAChR) in the induction of oscillatory field activity in the in vitro preparation of the rat hippocampus. Bath-application of a low concentration of nicotine (1 muM) to transversely-cut hippocampal slices produced persistent theta-frequency oscillations in area CA3 of the hippocampus. These oscillations were reduced by both GABA(A) receptor antagonists and ionotropic glutamate receptor antagonists, indicating the involvement of local GABAergic and glutamatergic neurons in the production of the rhythmic theta activity. The nicotine-induced theta activity was inhibited by non-selective nAChR antagonists and partially by an alpha7* nAChR antagonist. The induction of theta frequency oscillations in CA3 by nicotine was mimicked alpha7* nAChR agonists but not by non-alpha7* nAChR agonists. In conclusion, theta activity in the hippocampus may be promoted by tonic stimulation of alpha7* nAChRs, possibly via selective stimulation of theta-preferring interneurons in the hippocampus that express post-synaptic alpha7* nAChRs.

  18. Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide

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    Anne Gulbins

    2016-08-01

    Full Text Available Background/Aims: Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of major depressive disorder and functions as a target of antidepressants. Methods: Here, we investigated (i whether ceramide accumulates in endothelial cells in the neurogenetic zone of the hippocampus after glucocorticosterone-mediated stress, (ii whether ceramide is released into the extracellular space of the hippocampus and (iii whether extracellular ceramide inhibits neuronal proliferation. Ceramide was determined in endothelial cell culture supernatants or extracellular hippocampus extracts by a kinase assay. Endothelial ceramide in the hippocampus was analyzed by confocal microscopy of brain sections stained with Cy3-labelled anti-ceramide antibodies and FITC-Isolectin B4. Neuronal proliferation was measured by incubation of pheochromocytoma neuronal cells with culture supernatants and extracellular hippocampus extracts. Results: Treatment of cultured endothelial cells with glucocorticosterone induces a release of ceramide into the supernatant. Likewise, treatment of mice with glucocorticosterone triggers a release of ceramide into the extracellular space of the hippocampus. The release of ceramide is inhibited by concomitant treatment with the antidepressant amitriptyline, which also inhibits the activity of the acid sphingomyelinase. Studies employing confocal microscopy revealed that ceramide is formed and accumulates exclusively in endothelial cells in the hippocampus of stressed mice, a process that was again prevented by co-application of amitriptyline. Ceramide released in the culture supernatant or into the extracellular space of the

  19. Some of the experimental and clinical aspects of the effectsof the maternal diabetes on developing hippocampus

    Institute of Scientific and Technical Information of China (English)

    Javad Hami; Fatemeh Shojae; Saeed Vafaee-Nezhad; Nasim Lotfi; Hamed Kheradmand; Hossein Haghir

    2015-01-01

    Diabetes mellitus during pregnancy is associated with an increased risk of multiple congenital anomalies in progeny. There are sufficient evidence suggesting that the children of diabetic women exhibit intellectual and behavioral abnormalities accompanied by modification of hippocampus structure and function. Although, theexact mechanism by which maternal diabetes affectsthe developing hippocampus remains to be defined.Multiple biological alterations, including hyperglycemia,hyperinsulinemia, oxidative stress, hypoxia, and irondeficiency occur in pregnancies with diabetes and affectthe development of central nervous system (CNS) ofthe fetus. The conclusion from several studies is thatdisturbance in glucose and insulin homeostasis inmothers and infants are major teratogenic factor in thedevelopment of CNS. Insulin and Insulin-like growthfactor-1 (IGF-1) are two key regulators of CNS functionand development. Insulin and IGF-1 receptors (IR andIGF1R, respectively) are distributed in a highly specificpattern with the high density in some brain regionssuch as hippocampus. Recent researches have clearlyestablished that maternal diabetes disrupts the regulationof both IR and IGF1R in the hippocampus of ratnewborn. Dissecting out the mechanisms responsible formaternal diabetes-related changes in the developmentof hippocampus is helping to prevent from impairedcognitive and memory functions in offspring.

  20. Combined effects of electroacupuncture and anti-depression drugs on the hippocampus and frontal lobe

    Institute of Scientific and Technical Information of China (English)

    Dongmei Duan; Ya Tu; Shuang Jiao; Liping Chen

    2010-01-01

    Electroacupuncture (EA) has been clinically used to treat depression and has resulted in favorable effects in China. However, results from animal studies and pathology do not reflect the influence of electroacupuncture treatment on in vivo physiological functions. To thoroughly and dynamically observe pathological changes during depression, the present study established EA + fluoxetine and fluoxetine groups to observe depression in patients. 1H-magnetic resonance spectroscopy was utilized to determine the correlation between hippocampal frontal lobe metabolite changes and mental disorder scale. Results revealed significantly increased N-acetylaspartate (NAA)/creatine (Cr) in the bilateral hippocampus and right frontal lobe of depression patients treated with EA compared with fluoxetine. Changes in NAA/Cr in bilateral hippocampus and right frontal lobe in both groups, before and after treatment, negatively correlated with severity and curative effects. Choline/Cr changes in the bilateral frontal lobes of both groups were significant before and after treatment, but negatively correlated with curative effects. Choline/Cr changes in the bilateral hippocampus were significant in the EA + fluoxetine group before and after treatment, but negatively correlated with severity and the curative effects of depression. These results demonstrate abnormal biochemical metabolism in bilateral frontal lobes and hippocampus of depression patients, and show that EA significantly altered biochemical indices in the frontal lobes and hippocampus compared with fluoxetine.

  1. Fear of the unexpected: hippocampus mediates novelty-induced return of extinguished fear in rats.

    Science.gov (United States)

    Maren, Stephen

    2014-02-01

    Several lines of evidence indicate an important role for the hippocampus in the recovery of fear memory after extinction. For example, hippocampal inactivation prevents the renewal of fear to an extinguished conditioned stimulus (CS) when it is presented outside the extinction context. Renewal of extinguished responding is accompanied by associative novelty (an unexpected occurrence of a familiar CS in a familiar place), the detection of which may require the hippocampus. We therefore examined whether the hippocampus also mediates the recovery of extinguished fear caused by other unexpected events, including presenting a familiar CS in a novel context or presenting a novel cue with the CS in a familiar context (e.g., external disinhibition). Rats underwent Pavlovian fear conditioning and extinction using an auditory CS and freezing behavior served as the index of conditioned fear. In Experiment 1, conditioned freezing to the extinguished CS was renewed in a novel context and this was eliminated by intra-hippocampal infusions of the GABAA agonist, muscimol, prior to the test. In Experiment 2, muscimol inactivation of the hippocampus reduced the external disinhibition of conditioned freezing that occurred when a novel white noise accompanied the extinguished tone CS. Collectively, these results suggest that the hippocampus mediates the return of fear when extinguished CSs are unexpected, or when unexpected stimuli accompany CS presentation. Ultimately, a violation of expectations about when, where, and with what other stimuli an extinguished CS will occur may form the basis of spontaneous recovery, renewal, and external disinhibition.

  2. EFFECT OF VASOPRESSIN ON DELAYED NEURONAL DAMAGE IN HIPPOCAMPUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION IN GERBILS

    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉

    1996-01-01

    Mongolian gerbils were used as delayed neuronal damage (DND) animal models.At the end of 15 minute cerebral ischermia and at various reperfusion time ranging from 1 to 96 hours,the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassy.Furthermore,we also examined the effect of intracerebroventricular (ICV) injection of AVP,AVP antiserum on calcium,Na+,K+-ATP ase activity in the CA1 sector after ischemia and 96 hour reperfusion.The results showed that AVP Contents of CA1 sector of hippocampus during 6 to 96 hour recirculation,and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased.After ICV injection of AVP,the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased,and the Na+,K+-AT-tion of AVP antiserum,the water contenr and calcium in CA1 sector were significantly decreased as compared with that of control.These suggested that AVP was involved in the pathopysiologic process of DND in hippocampus following cerbral ischemia and reprfusion.Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca inos over-load of neuron and inhibit the Na+,K+-ATPase activity,thereby to exacerbate the DND in hippocampus.

  3. Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    ZHANG Yi-dan

    2012-04-01

    Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

  4. Expression of Toll-like receptor 4 in hippocampus of rat model with temporal lobe epilepsy

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    PAN Li-ping

    2013-12-01

    Full Text Available Objective To investigate the expression of Toll-like receptor 4 (TLR4 protein in hippocampus of rat model with temporal lobe epilepsy after status epilepticus (SE and explore its function in the pathogenesis of temporal lobe epilepsy. Methods Rat model with temporal lobe epilepsy was induced by lithium chloride (LiCl-pilocarpine. Total protein was extracted from hippocampus and rat brain slices were obtained at different time points (0, 1, 6, 12, 24, 48 h and 7, 10, 30, 50 d after SE. Western blotting and immunohistochemical staining were used for detection of the expression of TLR4 in the hippocampus. Results The results of Western blotting showed the TLR4 protein expression at 0, 1, 6, 12, 24, 48 h and 7, 10, 30 d after SE was higher than that in the control group (P 0.05. Conclusion TLR4 protein was mainly expressed in cytoplasm of pyramidal cells in CA3 area of hippocampus. TLR4 protein expression in the hippocampus was increased in varying degrees at different observation time points after SE, indicating that TLR4 may play an important role in the development of epilepsy.

  5. Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion.

    Science.gov (United States)

    Castro-Hernández, Javier; Adlard, Paul A; Finkelstein, David I

    2017-03-14

    The hippocampus has a significant association with memory, cognition and emotions. The dopaminergic projections from both the ventral tegmental area and substantia nigra are thought to be involved in hippocampal activity. To date, however, few studies have investigated dopaminergic innervation in the hippocampus or the functional consequences of reduced dopamine in disease models. Further complicating this, the hippocampus exhibits anatomical and functional differentiation along its dorso-ventral axis. In this work we investigated the role of dopamine on hippocampal long term potentiation using D-amphetamine, which stimulates dopamine release, and also examined how a dopaminergic lesion affects the synaptic transmission across the anatomic subdivisions of the hippocampus. Our findings indicate that a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced dopaminergic lesion has time-dependent effects and impacts mainly on the ventral region of the hippocampus, consistent with the density of dopaminergic innervation. Treatment with a preferential D3 receptor agonist pramipexole partly restored normal synaptic transmission and Long-Term Potentiation. These data suggest a new mechanism to explain some of the actions of pramipexole in Parkinson´s disease.

  6. Kv1.1 null mice have enlarged hippocampus and ventral cortex

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    Wang Fu-Hua

    2007-01-01

    Full Text Available Abstract Background Mutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy. Mice that express a malfunctional, truncated Kv1.1 (BALB/cByJ-Kv1.1mceph/mceph show a markedly enlarged hippocampus and ventral cortex in adulthood. Results To determine if mice lacking Kv1.1 also develop a brain enlargement similar to mceph/mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was then studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1mceph/mceph, BALB/cByJ-Kv1.1mceph/+, BALB.C3HeB -Kv1.1-/+ and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex. Conclusion Total absence of Kv1.1 can induce excessive overgrowth of hippocampus and ventral cortex in mice with a BALB/cByJ background, while mice with one wild type Kv1.1 allele develop normal-sized brains.

  7. Denervated hippocampus provides a favorable microenvironment for neuronal differentiation of endogenous neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xiao Han; Xiang Cheng; Xue-feng Tan; He-yan Zhao; Xin-hua Zhang

    2016-01-01

    Fimbria-fornix transection induces both exogenous and endogenous neural stem cells to differentiate into neurons in the hippocampus. This indicates that the denervated hippocampus provides an environment for neuronal differentiation of neural stem cells. However, the pathways and mechanisms in this process are still unclear. Seven days after ifmbria fornix transection, our reverse transcription polymerase chain reaction, western blot assay, and enzyme linked immunosorbent assay results show a signiifcant increase in ciliary neurotrophic factor mRNA and protein expression in the denervated hippocampus. Moreover, neural stem cells derived from hippocampi of fetal (em-bryonic day 17) Sprague-Dawley rats were treated with ciliary neurotrophic factor for 7 days, with an increased number of microtubule associated protein-2-positive cells and decreased number of glial ifbrillary acidic protein-positive cells detected. Our results show that cili-ary neurotrophic factor expression is up-regulated in the denervated hippocampus, which may promote neuronal differentiation of neural stem cells in the denervated hippocampus.

  8. Novel experience induces persistent sleep-dependent plasticity in the cortex but not in the hippocampus

    Directory of Open Access Journals (Sweden)

    Sidarta Ribeiro

    2007-10-01

    Full Text Available Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS and rapid eye movement (REM sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP, and expression levels of plasticity-related immediate-early genes (IEG arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours than in the hippocampus (minutes. During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10-14 Hz but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time.

  9. 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.

  10. Ultrastructural abnormalities in CA1 hippocampus caused by deletion of the actin regulator WAVE-1.

    Directory of Open Access Journals (Sweden)

    Diána Hazai

    Full Text Available By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.

  11. 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.

  12. Mitochondrial plasticity of the hippocampus in a generic rat model of depression after antidepressant treatment

    DEFF Research Database (Denmark)

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

    2012-01-01

    investigated the changes in mitochondrial plasticity and its correlation to morphological alterations of neuroplasticity in the hippocampus, both associated with a depressive phenotype, and after treatment, with antidepressant imipramine. Design-based stereological methods were used to estimate the number...... and volume of mitochondria in CA1 of the hippocampus in two different strains of rats, the Sprague-Dawley (SD) and Flinders rats, which display a genetic susceptibility to depressive behavior, the Flinders-sensitive line (FSL) and their corresponding controls, the Flinders-resistant line (FRL). Results...... of mitochondrial plasticity in the hippocampus and antidepressant treatment may counteract with the structural impairments. Moreover, the changes in mitochondrial morphology and number are a consistent feature of neuroplasticity. Synapse, 2013. © 2012 Wiley Periodicals, Inc....

  13. 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

    vertical sections from the hippocampus. The volume of hippocampal neurons was estimated using the rotator principle on 40 microm thick plastic vertical uniform random sections and corrected for tissue shrinkage. Application of the proposed new design should result in more accurate estimates of neuron......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......; however, the classical optical fractionator design may be affected by tissue deformation in the z-axis of the section. In this study, we applied an improved optical fractionator design to estimate total number of neurons on 100 microm thick vibratome sections that had been deformed, in the z...

  14. 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

    2013-12-12

    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.

  15. An Upside to Reward Sensitivity: The Hippocampus Supports Enhanced Reinforcement Learning in Adolescence.

    Science.gov (United States)

    Davidow, Juliet Y; Foerde, Karin; Galván, Adriana; Shohamy, Daphna

    2016-10-05

    Adolescents are notorious for engaging in reward-seeking behaviors, a tendency attributed to heightened activity in the brain's reward systems during adolescence. It has been suggested that reward sensitivity in adolescence might be adaptive, but evidence of an adaptive role has been scarce. Using a probabilistic reinforcement learning task combined with reinforcement learning models and fMRI, we found that adolescents showed better reinforcement learning and a stronger link between reinforcement learning and episodic memory for rewarding outcomes. This behavioral benefit was related to heightened prediction error-related BOLD activity in the hippocampus and to stronger functional connectivity between the hippocampus and the striatum at the time of reinforcement. These findings reveal an important role for the hippocampus in reinforcement learning in adolescence and suggest that reward sensitivity in adolescence is related to adaptive differences in how adolescents learn from experience.

  16. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  17. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  18. Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A. (Hoffmann-La Roche, Inc., Nutley, NJ (USA). Dept. of Pharmacology); Rainbow, T.C. (Pennsylvania Univ., Philadelphia (USA). School of Medicine); McEwen, B.S. (Rockefeller Univ., New York (USA))

    1985-04-22

    The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on neurotransmitter receptors was studied in dorsal hippocampus of rat using quantitative autoradiography. ADX for one week causes an increase in (/sup 3/H)5-HT binding to 5-HT/sub 1/ receptors which is significant in the CA1 cell field. CORT treatment of ADX rats for 3-5 days results in localized reductions of (/sup 3/H)5-HT binding including a partial reversal of the increase observed after ADX in CA1. CORT treatment of ADX animals also decreases binding of (/sup 3/H)QNB to muscarinic receptors in the dorsal hippocampus, with a significant effect in an area designated as subiculum. No influence of CORT was detected on (/sup 3/H)prazosin binding to alpha/sub 1/ adrenergic receptors in dorsal hippocampus. Possible mechanisms for hormone effects on neurotransmitter receptor levels are discussed.

  19. Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults.

    Science.gov (United States)

    Witte, A Veronica; Köbe, Theresa; Kerti, Lucia; Rujescu, Dan; Flöel, Agnes

    2016-02-01

    The single nucleotide polymorphism rs17070145 within the KIBRA gene (kidney and brain expressed protein) has been associated with variations in memory functions and related brain areas. However, previous studies yielded conflicting results, which might be due to divergent sample characteristics or task-specific effects. Therefore, we aimed to determine the impact of KIBRA genotype on learning and memory formation, and volume, microstructural integrity and functional connectivity (FC) of the hippocampus and its subfields in a well-characterized cohort of healthy older adults. One-hundred and forty subjects (72 women, age 50-80) were KIBRA genotyped and memory was tested using the Auditory Verbal Learning Task. Also, subjects underwent structural and resting-state functional magnetic resonance imaging at 3T. Subfields were delineated using automated segmentation (FreeSurfer software). Microstructural integrity was measured using mean diffusivity (MD) derived from diffusion tensor images. Seed-based analyses were used to assess FC patterns of the hippocampus. KIBRA T-allele carriers showed a trend for better memory performance, and in the hippocampus significantly higher volumes and partly lower MD, indicative for better microstructure, compared with non-T-allele carriers in the cornu ammonis (CA)2/3 and CA4/dentate gyrus subfields (all P⩽0.008, Bonferroni corrected). Also, T-allele carriers exhibited lower FC of the left hippocampus with areas outside the synchronized HC network. In sum, we could show for the first time that older T-allele carriers exhibited larger volumes and better microstructure within those hippocampus subfields that are implicated in long-term potentiation and neurogenesis, key features of memory processes. Moreover, T-allele carriers showed a more selective FC network of the hippocampus.

  20. Acetylcholine release in the hippocampus and prelimbic cortex during acquisition of a socially transmitted food preference.

    Science.gov (United States)

    Gold, P E; Countryman, R A; Dukala, D; Chang, Q

    2011-10-01

    Interference with cholinergic functions in hippocampus and prefrontal cortex impairs learning and memory for social transmission of food preference, suggesting that acetylcholine (ACh) release in the two brain regions may be important for acquiring the food preference. This experiment examined release of ACh in the hippocampus and prefrontal cortex of rats during training for social transmission of food preference. After demonstrator rats ate a food with novel flavor and odor, a social transmission of food preference group of rats was allowed to interact with the demonstrators for 30 min, while in vivo microdialysis collected samples for later measurement of ACh release with HPLC methods. A social control group observed a demonstrator that had eaten food without novel flavor and odor. An odor control group was allowed to smell but not ingest food with novel odor. Rats in the social transmission but not control groups preferred the novel food on a trial 48 h later. ACh release in prefrontal cortex, with probes that primarily sampled prelimbic cortex, did not increase during acquisition of the social transmission of food preference, suggesting that training-initiated release of ACh in prelimbic cortex is not necessary for acquisition of the food preference. In contrast, ACh release in the hippocampus increased substantially (200%) upon exposure to a rat that had eaten the novel food. Release in the hippocampus increased significantly less (25%) upon exposure to a rat that had eaten normal food and did not increase significantly in the rats exposed to the novel odor; ACh release in the social transmission group was significantly greater than that of the either of the control groups. Thus, ACh release in the hippocampus but not prelimbic cortex distinguished well the social transmission vs. control conditions, suggesting that cholinergic mechanisms in the hippocampus but not prelimbic cortex are important for acquiring a socially transmitted food preference. Copyright

  1. The role of the human hippocampus in familiarity-based and recollection-based recognition memory.

    Science.gov (United States)

    Wixted, John T; Squire, Larry R

    2010-12-31

    The ability to recognize a previously encountered stimulus is dependent on the structures of the medial temporal lobe and is thought to be supported by two processes, recollection and familiarity. A focus of research in recent years concerns the extent to which these two processes depend on the hippocampus and on the other structures of the medial temporal lobe. One view holds that the hippocampus is important for both processes, whereas a different view holds that the hippocampus supports only the recollection process and the perirhinal cortex supports the familiarity process. One approach has been to study patients with hippocampal lesions and to contrast old/new recognition (which can be supported by familiarity) to free recall (which is supported by recollection). Despite some early case studies suggesting otherwise, several group studies have now shown that hippocampal patients exhibit comparable impairments on old/new recognition and free recall. These findings suggest that the hippocampus is important for both recollection and familiarity. Neuroimaging studies and Receiver Operating Characteristic analyses also initially suggested that the hippocampus was specialized for recollection, but these studies involved a strength confound (strong memories have been compared to weak memories). When steps are taken to compare strong recollection-based memories with strong familiarity-based memories, or otherwise control for memory strength, evidence for a familiarity signal (as well as a recollection signal) is evident in the hippocampus. These findings suggest that the functional organization of the medial temporal lobe is probably best understood in terms unrelated to the distinction between recollection and familiarity.

  2. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    Science.gov (United States)

    Dal Bosco, Lidiane; Weber, Gisele E; Parfitt, Gustavo M; Cordeiro, Arthur P; Sahoo, Sangram K; Fantini, Cristiano; Klosterhoff, Marta C; Romano, Luis Alberto; Furtado, Clascídia A; Santos, Adelina P; Monserrat, José M; Barros, Daniela M

    2015-01-01

    Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the

  3. Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

    Directory of Open Access Journals (Sweden)

    Lidiane Dal Bosco

    Full Text Available Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of

  4. 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.

  5. Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

    Science.gov (United States)

    Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-08-01

    Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window.

  6. Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

    Science.gov (United States)

    Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

  7. 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.

  8. Bilateral injections of beta A(25-35) + IBO into the hippocampus disrupts acquisition of spatial learning in the rat.

    Science.gov (United States)

    Dornan, W A; Kang, D E; McCampbell, A; Kang, E E

    1993-11-18

    Focal deposits of beta-amyloid (beta A) in the hippocampus have been implicated in Alzheimer's disease. In this study we assessed the effects of bilateral injections into the hippocampus of beta A(25-35), a combination of beta A(25-35) with ibotenic acid (IBO), and IBO on spatial learning in the rat. Bilateral injections of beta A(25-35) into the hippocampus together with IBO (which by itself has no neurotoxic effects) produced a dramatic disruption in the acquisition of a spatial learning in the rat. Separate injections into the hippocampus of beta A(25-35) or the incubated form of beta A(25-35) alone failed to significantly affect maze acquisition in the rat. Histological examination revealed that only the combination of beta A(25-35) with IBO produced a lesion along with focal deposits in the hippocampus.

  9. Testing for direct and indirect effects of mate choice by manipulating female choosiness.

    Science.gov (United States)

    Maklakov, Alexei A; Arnqvist, Göran

    2009-12-01

    Despite a massive research effort, our understanding of the evolution of female mate choice remains incomplete [1, 2]. A central problem is that the predominating empirical research tradition has focused on male traits, yet the key question is whether female choice traits are maintained because of direct effects on female fitness or because of indirect genetic effects in offspring that may be associated with such traits. Here, we address this question by using a novel research strategy that employs experimental phenotypic manipulation of a female choice trait in an insect model system, the seed beetle Callosobruchus chinensis (Coleoptera: Bruchidae). We show that females with increased efficiency of choice enjoy strongly elevated fitness compared to females with reduced choice efficiency. In contrast, we found no effects of female choice efficiency on offspring fitness. Our results show that female choice is maintained by direct selection in females in this system, whereas indirect selection is relatively weak at most. We suggest that phenotypic engineering of female choice traits can greatly advance our ability to elucidate the relative importance of direct and indirect selection for the maintenance of female choice.

  10. Sexy males and choosy females on exploded leks: correlates of male attractiveness in the Little Bustard.

    Science.gov (United States)

    Jiguet, Frédéric; Bretagnolle, Vincent

    2014-03-01

    In their choice of mates, females may use alternative tactics, including a comparative assessment of males in a population, using one or several relative preference criteria. Traits involved in female choice should presumably be variable between, but not within males, thus potentially providing reliable cues of male identity and quality for prospecting females. In lekking species, sexual selection is usually intense, and females can freely choose mates. Studying the Little Bustard Tetrax tetrax, a bird with an exploded lek mating system, we first identified male phenotypic traits that showed higher among, than within variation (plumage pattern, display rates and call structure). Among those and other traits (ornaments and their symmetry, body condition, lek spatial organization and territory quality), we identified phenotypic traits that correlated with male attractiveness toward females. At least four phenotypic male traits were correlated with female attraction, i.e. body condition, lek attendance, ornamental symmetry and display rates. Traits related to the initial female attraction on male territory seem to differ from traits related to the decision of females to stay in the territory of attractive males.

  11. Choosy Wolves? Heterozygote Advantage But No Evidence of MHC-Based Disassortative Mating.

    Science.gov (United States)

    Galaverni, Marco; Caniglia, Romolo; Milanesi, Pietro; Lapalombella, Silvana; Fabbri, Elena; Randi, Ettore

    2016-03-01

    A variety of nonrandom mate choice strategies, including disassortative mating, are used by vertebrate species to avoid inbreeding, maintain heterozygosity and increase fitness. Disassortative mating may be mediated by the major histocompatibility complex (MHC), an important gene cluster controlling immune responses to pathogens. We investigated the patterns of mate choice in 26 wild-living breeding pairs of gray wolf (Canis lupus) that were identified through noninvasive genetic methods and genotyped at 3 MHC class II and 12 autosomal microsatellite (STR) loci. We tested for deviations from random mating and evaluated the covariance of genetic variables at functional and STR markers with fitness proxies deduced from pedigree reconstructions. Results did not show evidences of MHC-based disassortative mating. Rather we found a higher peptide similarity between mates at MHC loci as compared with random expectations. Fitness values were positively correlated with heterozygosity of the breeders at both MHC and STR loci, whereas they decreased with relatedness at STRs. These findings may indicate fitness advantages for breeders that, while avoiding highly related mates, are more similar at the MHC and have high levels of heterozygosity overall. Such a pattern of MHC-assortative mating may reflect local coadaptation of the breeders, while a reduction in genetic diversity may be balanced by heterozygote advantages. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. 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…

  13. Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

    Science.gov (United States)

    Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

    2013-01-01

    The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

  14. The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects

    Science.gov (United States)

    Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

    2016-01-01

    Background: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. Methods: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Results: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Conclusions: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals. PMID:27076895

  15. Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia.

    Science.gov (United States)

    Wu, Lin; Feng, Xiao-Tao; Hu, Yue-Qiang; Tang, Nong; Zhao, Qing-Shan; Li, Tian-Wei; Li, Hai-Yuan; Wang, Qing-Bi; Bi, Xin-Ya; Cai, Xin-Kun

    2015-09-01

    Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

  16. 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…

  17. D-Cycloserine Enhances Memory Consolidation of Hippocampus-Dependent Latent Extinction

    Science.gov (United States)

    Gabriele, Amanda; Packard, Mark G.

    2007-01-01

    Adult male Long-Evans rats were trained to run in a straight-alley maze for food reward and subsequently received hippocampus-dependent latent extinction training. Immediately following latent extinction, rats received peripheral injections of the NMDA receptor partial agonist D-cycloserine (DCS, 15 mg/kg), or saline. Twenty-four hours later, rats…

  18. 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.

  19. Early repeated maternal separation induces alterations of hippocampus reelin expression in rats

    Indian Academy of Sciences (India)

    Jianlong Zhang; Lina Qin; Hu Zhao

    2013-03-01

    The long-term effects of repeated maternal separation (MS) during early postnatal life on reelin expression in the hippocampus of developing rats were investigated in the present study. MS was carried out by separating Wistar rat pups singly from their mothers for 3 h a day during postnatal days (PND) 2–14. Reelin mRNA and protein levels in the hippocampus were determined using qRT-PCR and Western blotting, at PND 22, PND 60 and PND 90. MS resulted in the loss of body weight in the developing rats, and reelin mRNA and protein levels in the hippocampus generally were down-regulated over the developing period, but the reelin mRNA and protein levels in the hippocampus of 90-day-old male rats were up-regulated. These findings suggest that the long-term effects of MS on the expression levels of hippocampal reelin mRNA and protein depends on the age at which the stressed rats’ brains were collected; reelin had important implications for the maternal-neonate interaction needed for normal brain development. In conclusion, repeated MS occurring during early postnatal life may cause the alterations of hippocampal reelin expression with the increasing age of developing rats.

  20. γIsoform-Selective Changes in PKC Immunoreactivity after Trace Eyeblink Conditioning in the Rabbit Hippocampus

    NARCIS (Netherlands)

    Zee, E.A. van der; Kronforst-Collins, M.A.; Maizels, E.T.; Hunzicker-Dunn, M.; Disterhoft, J.F.

    1997-01-01

    An immunocytochemical examination of the rabbit hippocampus was done to determine which of the Ca2+-dependent protein kinase C (PKC) isoforms (PKCα, -βI, -βII, or -γ) are involved in associative learning. The hippocampally dependent trace eyeblink conditioning task was used for behavioral training,

  1. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    Science.gov (United States)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

  2. Appearance and incomplete label matching for diffeomorphic template based hippocampus segmentation.

    Science.gov (United States)

    Pluta, John; Avants, Brian B; Glynn, Simon; Awate, Suyash; Gee, James C; Detre, John A

    2009-06-01

    We present a robust, high-throughput, semiautomated template-based protocol for segmenting the hippocampus in temporal lobe epilepsy. The semiautomated component of this approach, which minimizes user effort while maximizing the benefit of human input to the algorithm, relies on "incomplete labeling." Incomplete labeling requires the user to quickly and approximately segment a few key regions of the hippocampus through a user-interface. Subsequently, this partial labeling of the hippocampus is combined with image similarity terms to guide volumetric diffeomorphic normalization between an individual brain and an unbiased disease-specific template, with fully labeled hippocampi. We solve this many-to-few and few-to-many matching problem, and gain robustness to inter and intrarater variability and small errors in user labeling, by embedding the template-based normalization within a probabilistic framework that examines both label geometry and appearance data at each label. We evaluate the reliability of this framework with respect to manual labeling and show that it increases minimum performance levels relative to fully automated approaches and provides high inter-rater reliability. Thus, this approach does not require expert neuroanatomical training and is viable for high-throughput studies of both the normal and the highly atrophic hippocampus.

  3. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT RAT HIPPOCAMPUS BUT DOES NOT IMPAIR SPATIAL LEARNING.

    Science.gov (United States)

    It has long been heralded that the mature brain does not generate new neurons, it only loses them as a function of injury, disease and age. An exciting recent finding in neuroscience has been that the dentate granule cell layer of the hippocampus has the distinctive property of ...

  4. In Vitro Antioxidant Activity and In Vivo Anti-Fatigue Effect of Sea Horse (Hippocampus) Peptides.

    Science.gov (United States)

    Guo, Zebin; Lin, Duanquan; Guo, Juanjuan; Zhang, Yi; Zheng, Baodong

    2017-03-18

    This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material-liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus peptide prepared by papain digestion exhibited the highest 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging rate (71.89% ± 1.50%) and strong hydroxyl radical scavenging rate (75.53% ± 0.98%), compared to those prepared by five other commonly used enzymes (i.e., trypsin, neutral protease, compound protease, flavorzyme, and alkaline protease). Additionally, maximum antioxidant activity of Hippocampus polypeptide prepared by papain digestion was reached after hydrolysis for 40 min at pH 6.0 and 60 °C of the reaction system by using 2000 U/g enzyme and a material-liquid ratio of 1:15. Moreover, compared with the control group, Hippocampus peptide prolonged the swimming time by 33%-40%, stabilized the blood glucose concentration, increased liver glycogen levels, and decreased blood lactate levels and blood urea nitrogen levels in mice (p antioxidant and anti-fatigue activity.

  5. Time-of-day-dependent enhancement of adult neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    So-ichi Tamai

    Full Text Available BACKGROUND: Adult neurogenesis occurs in specific regions of the mammalian brain such as the dentate gyrus of the hippocampus. In the neurogenic region, neural progenitor cells continuously divide and give birth to new neurons. Although biological properties of neurons and glia in the hippocampus have been demonstrated to fluctuate depending on specific times of the day, it is unclear if neural progenitors and neurogenesis in the adult brain are temporally controlled within the day. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that in the dentate gyrus of the adult mouse hippocampus, the number of M-phase cells shows a day/night variation throughout the day, with a significant increase during the nighttime. The M-phase cell number is constant throughout the day in the subventricular zone of the forebrain, another site of adult neurogenesis, indicating the daily rhythm of progenitor mitosis is region-specific. Importantly, the nighttime enhancement of hippocampal progenitor mitosis is accompanied by a nighttime increase of newborn neurons. CONCLUSIONS/SIGNIFICANCE: These results indicate that neurogenesis in the adult hippocampus occurs in a time-of-day-dependent fashion, which may dictate daily modifications of dentate gyrus physiology.

  6. Hippocampus leads ventral striatum in replay of place-reward information

    NARCIS (Netherlands)

    C.S. Lansink; P.M. Goltstein; J.V. Lankelma; B.L. McNaughton; C.M.A. Pennartz

    2009-01-01

    Associating spatial locations with rewards is fundamental to survival in natural environments and requires the integrity of the hippocampus and ventral striatum. In joint multineuron recordings from these areas, hippocampal-striatal ensembles reactivated together during sleep. This process was espec

  7. Enriched environment induces higher CNPase positive cells in aged rat hippocampus.

    Science.gov (United States)

    Zhao, Yuan-Yu; Shi, Xiao-Yan; Zhang, Lei; Wu, Hong; Chao, Feng-Lei; Huang, Chun-Xia; Gao, Yuan; Qiu, Xuan; Chen, Lin; Lu, Wei; Tang, Yong

    2013-10-25

    It had been reported that enriched environment was beneficial for the brain cognition and for the neurons and synapses in hippocampus. Previous study reported that the oligodendrocyte density in hippocampus was increased when the rats were reared in the enriched environment from weaning to adulthood. However, biological conclusions based on density were difficult to interpret because the changes in density could be due to an alteration of total quantity and/or an alteration in the reference volume. In the present study, we used unbiased stereological methods to investigate the effect of enriched environment on the total number of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) positive cells in CA1 and dentate gyrus (DG) of the hippocampus in aged rats. Our results indicated that there was significant difference in the total numbers of CNPase positive cells in both CA1 and DG between enriched environment group and standard environment group. The present study provided the first evidence for the protective effects of enriched environment on the CNPase positive cells in aged hippocampus.

  8. REDUCTION OF ADENOSINE-A1-RECEPTORS IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMER HIPPOCAMPUS

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alz

  9. Comparative efficacy of four anaesthetic agents in the yellow seahorse, Hippocampus kuda (Bleeker, 1852)

    Digital Repository Service at National Institute of Oceanography (India)

    Pawar, H.B.; Sanaye, S.V.; Sreepada, R.A.; Harish, V.; Suryavanshi, U.; Tanu; Ansari, Z.A.

    -bred yellow seahorse, Hippocampus kuda (Bleeker, 1852). The lowest effective concentrations based on the efficacy criteria of complete anaesthetic induction within 180 s and recovery within 300 s were determined to be 125 mg L sup(-1) (induction 115 + or - 16...

  10. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  11. Memory signals are temporally dissociated in and across human hippocampus and perirhinal cortex.

    Science.gov (United States)

    Staresina, Bernhard P; Fell, Juergen; Do Lam, Anne T A; Axmacher, Nikolai; Henson, Richard N

    2012-07-01

    In the endeavor to understand how our brains enable our multifaceted memories, much controversy surrounds the contributions of the hippocampus and perirhinal cortex (PrC). We recorded functional magnetic resonance imaging (fMRI) in healthy controls and intracranial electroencephalography (EEG) in patients during a recognition memory task. Although conventional fMRI analysis showed indistinguishable roles of the hippocampus and PrC in familiarity-based item recognition and recollection-based source retrieval, event-related fMRI and EEG time courses revealed a clear temporal dissociation of memory signals in and across these regions. An early source retrieval effect was followed by a late, post-decision item novelty effect in hippocampus, whereas an early item novelty effect was followed by a sustained source retrieval effect in PrC. Although factors such as memory strength were not experimentally controlled, the temporal pattern across regions suggests that a rapid item recognition signal in PrC triggers a source retrieval process in the hippocampus, which in turn recruits PrC representations and/or mechanisms, evidenced here by increased hippocampal-PrC coupling during source recognition.

  12. The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model.

    Science.gov (United States)

    Kwak, Sung-Eun; Kim, Ji-Eun; Choi, Hui-Chul; Song, Hong-Ki; Kim, Yeong-In; Jo, Seung-Mook; Kang, Tae-Cheon

    2008-01-01

    During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.

  13. The effects of 30 mT electromagnetic fields on hippocampus cells of rats

    Directory of Open Access Journals (Sweden)

    Farzaneh Teimori

    2016-01-01

    Conclusions: Similar to numerous studies that have reported the effects of EMFs on nerves system, it was also confirmed in this lecture. Hence, the hippocampus which is important in regulating emotions, behavior, motivation, and memory functions, may be impaired by the negative impacts of EMFs.

  14. REDUCTION OF ADENOSINE-A1-RECEPTORS IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMER HIPPOCAMPUS

    NARCIS (Netherlands)

    JAARSMA, D; SEBENS, JB; KORF, J

    1991-01-01

    The cells of origin of the perforant pathway are destroyed in Alzheimer's disease (AD). In rat the adenosine A1-receptors are specifically localized on the perforant path terminals in the molecular layer of the dentate gyrus. In the present study the density of A1-receptors in the hippocampus of Alz

  15. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT RAT HIPPOCAMPUS BUT DOES NOT IMPAIR SPATIAL LEARNING.

    Science.gov (United States)

    It has long been heralded that the mature brain does not generate new neurons, it only loses them as a function of injury, disease and age. An exciting recent finding in neuroscience has been that the dentate granule cell layer of the hippocampus has the distinctive property of ...

  16. Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

    Institute of Scientific and Technical Information of China (English)

    Yan Yu; Changchun Zeng; Siyun Shu; Xuemei Liu; Chuhua Li

    2014-01-01

    Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-afifnity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inlfammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di-vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunolfuorescence showed high expression of the substance P receptor, neuro-kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen-dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi-tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.

  17. 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.

  18. Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus

    NARCIS (Netherlands)

    Michailidou, Iliana; Willems, Janske G P; Kooi, Evert-Jan; van Eden, Corbert; Gold, Stefan M; Geurts, Jeroen J G; Baas, Frank; Huitinga, I.; Ramaglia, Valeria

    2015-01-01

    OBJECTIVE: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, leading to memory impairment in up to 65% of patients. Memory dysfunction in MS has been associated with loss of synapses in the hippocampus, but its molecular basis is unknown. Accumulating evidence suggest

  19. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

    Science.gov (United States)

    Eid, Tore; Ghosh, Arko; Wang, Yue; Beckström, Henning; Zaveri, Hitten P; Lee, Tih-Shih W; Lai, James C K; Malthankar-Phatak, Gauri H; de Lanerolle, Nihal C

    2008-08-01

    An excess of extracellular glutamate in the hippocampus has been linked to the generation of recurrent seizures and brain pathology in patients with medically intractable mesial temporal lobe epilepsy (MTLE). However, the mechanism which results in glutamate excess in MTLE remains unknown. We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically involved in the pathophysiology of the disease. To further explore the role of glutamine synthetase in MTLE we created a novel animal model of hippocampal glutamine synthetase deficiency by continuous (approximately 28 days) microinfusion of methionine sulfoximine (MSO: 0.625 to 2.5 microg/h) unilaterally into the hippocampus in rats. This treatment led to a deficiency in hippocampal glutamine synthetase activity by 82-97% versus saline. The majority (>95%) of the MSO-treated animals exhibited recurrent seizures that continued for several weeks. Some of the MSO-treated animals exhibited neuropathological features that were similar to mesial temporal sclerosis, such as hippocampal atrophy and patterned loss of hippocampal neurons. However, many MSO-treated animals displayed only minimal injury to the hippocampus, with no clear evidence of mesial temporal sclerosis. These findings support the hypothesis that a deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, and that restoration of glutamine synthetase may represent a novel approach to therapeutic intervention in this disease.

  20. An immunohistochemical study of parvalbumin containing interneurons in the gerbil hippocampus after cerebral ischemia.

    Science.gov (United States)

    Araki, T; Kato, H; Liu, X H; Kogure, K; Kato, K; Itoyama, Y

    1994-09-01

    We investigated postischemic changes of non-pyramidal neurons in the gerbil hippocampus 1 h - 7 days after 10 min of cerebral ischemia, with parvalbumin and microtubule-associated protein 2 (MAP2)-immunohistochemistry. Parvalbumin-immunoreactive interneurons in the hippocampus were unaffected up to 24 h after ischemia. A slight reduction of the immunoreactivity in neuronal processes was seen in the hippocampal CA1 sector 48 h after ischemia. Seven days after ischemia, a marked loss of parvalbumin-immunoreactive interneurons was observed in the hippocampal CA1 and CA3 sectors. Furthermore, reduced staining in the dentate granular and molecular layers was observed. MAP2-immunoreactive pyramidal neurons in the hippocampus were unchanged up to 48 h after ischemia. Seven days after ischemia, a severe loss of MAP2 immunoreactivity was found in the hippocampal CA1 and CA3 neurons and dentate hilar neurons. However, scattered CA1 neurons, most likely interneurons, preserved MAP2 immunoreactivity. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin-immunoreactive interneurons in the hippocampus. Furthermore, some interneurons seem to lose parvalbumin synthesis. Although dentate granule cells are resistant to ischemia, considerable reductions of afferent input was suggested by parvalbumin staining.

  1. GFR alpha-1 is expressed in parvalbumin GABAergic neurons in the hippocampus.

    Science.gov (United States)

    Sarabi, A; Hoffer, B J; Olson, L; Morales, M

    2000-09-22

    Glial cell line derived neurotrophic factor (GDNF) is a potent survival factor for several types of neurons. GDNF binds with high affinity to GDNF-family receptor alpha-1 (GFR alpha-1). This receptor is expressed in different areas of the brain, including the hippocampus and dentate gyrus. By using in situ hybridization and immunohistochemistry, we found that 19% to 37% of glutamic acid decarboxylase (GAD) expressing neurons co-expressed GFR alpha-1 in the hippocampus. GFR alpha-1/GAD co-expression was found mainly in the stratum (s) pyramidale (29-37%) and s. oriens (20-25%). Further characterization of GFR alpha-1 expressing interneurons, based on their calcium-binding protein immunoreactivity, demonstrated that many parvalbumin (PV) immunoreactive neurons express GFR alpha-1 in the s. pyramidale of CA1 (72%), CA2 (70%) and CA3 (70%) subfields of the hippocampus. GFR alpha-1/PV double labeled neurons were also detected in the s. oriens of CA1 (52%), CA2 (27%) and CA3 (36%) subfields. The expression of GFR alpha-1 in principal neurons and in a specific sub-population of GABAergic neurons (PV-containing neurons) suggest that GDNF might modulate, in a selective manner, functions of the entire adult hippocampus.

  2. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  3. Manifold learning for atlas selection in multi-atlas-based segmentation of hippocampus

    Science.gov (United States)

    Hoang Duc, Albert K.; Modat, Marc; Leung, Kelvin K.; Kadir, Timor; Ourselin, Sébastien

    2012-02-01

    Alzheimer's disease (AD) severely affects the hippocampus: it loses mass and shrinks as the disease advances. Thus delineation of the hippocampus is an important task in the clinical study of AD. Because of its simplicity and good performance, multi-atlas based segmentation has become a popular approach for medical image segmentation. We propose to use manifold learning for atlas selection in the framework of multi-atlas based segmentation. The framework only benefits when selecting atlases similar to the target image. Since manifold learning assigns each image a coordinate in low-dimensional space by respecting the neighborhood relationship, it is well suited for atlas selection. The key contribution is that we use manifold learning based on a metric derived from non-rigid transformation as the resulting embedding better captures deformations or shape differences between images than similarity measures based on voxel intensity. The proposed method is evaluated in a leave-one-out experiment on a set of 110 hippocampus images; we report mean Dice score of 0.9114 (0.0227). The method was validated against a state-of-the-art method for hippocampus segmentation.

  4. Relative binding affinity of steroids for the corticosterone receptor system in rat hippocampus

    NARCIS (Netherlands)

    De Kloet, E R; Veldhuis, H D; Wagenaars, J L; Bergink, E W

    1984-01-01

    In cytosol of the hippocampus corticosterone displays highest affinity for the sites that remain available for binding in the presence of excess RU 26988, which is shown to be a "pure" glucocorticoid. A rather high affinity (greater than or equal to 25%) was found for 11 beta-hydroxyprogesterone, 21

  5. Localization of glucocorticoid receptor messenger ribonucleic acid in hippocampus of rat brain using in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Yang, G.; Matocha, M.F.; Rapoport, S.I.

    1988-08-01

    An in situ hybridization procedure was applied to quantify glucocorticoid receptor (GR) mRNAs in the hippocampus of rat brain. Hybridization was carried out using a radiolabeled antisense probe complementary to the rat liver GR gene. The specificity of the method was validated by showing: 1) a high cellular grain density in sections hybridized with an antisense but not a sense probe; 2) agreement between the experimental and theoretical temperature at which 50% of the hybrids melted, and 3) a high signal distribution of GR mRNA in the hippocampus, a region of brain known to preferentially concentrate steroid hormones. Within the hippocampus, however, subregional differences in hybridization densities were observed. Quantitative autoradiography indicated that the average neuronal silver grain number was highest in the pyramidal cell layers of CA2 and CA4 and lowest in those of CA1 and CA3. Also, there was a significant difference in the average grain number between all of the cell fields except for that between CA2 and CA4. These results show that contiguous but neuroanatomically distinct cell fields of the hippocampus express different levels of GR transcripts, and indicate that differential regulation of GR expression occurs in subpopulations of hippocampal neurons.

  6. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  7. Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to autobiographic test items.

    Science.gov (United States)

    Rekkas, P Vivien; Constable, R Todd

    2006-10-16

    The purpose of this experiment was to assess the effects of probe familiarity, the consequences of having recently retrieved an autobiographic memory (AM), on subsequent recall. This was accomplished by replicating an earlier imaging experiment, using the same participants and memory probes. Subtractions between sessions showed significant pre-exposure effects (i.e., drop in BOLD signal intensity) in the prefrontal cortex, thalamus, cerebellum and other brain structures. Further, region of interest (ROI) analysis illustrated a significant decrease in neural activity in the hippocampus in both conditions. The results are discussed in terms of the pre-scan interview technique, a method applied in AM research to procure personal information. Although invaluable, we emphasize it must be used with caution as it can result in a loss of power. The widespread use of this method in AM research may explain why studies often fail to find evidence of significant responding in the hippocampus in response to memory probes. Alternatively, when activity in the hippocampus is reported, it often fails to differentiate between recent and remote memories. This point is of particular importance to the on-going consolidation debate, as it often centers on a failure to detect an effect in the hippocampus in one or both conditions.

  8. Effects of soft-diet feeding on BDNF expression in hippocampus of mice.

    Science.gov (United States)

    Yamamoto, Tetsu; Hirayama, Akihiko; Hosoe, Nobuo; Furube, Masaru; Hirano, Shusuke

    2008-11-01

    Our previous study showed that mice fed a soft diet after weaning had reduced synaptic connections in the hippocampal formation and impaired spatial learning ability after 3 months of age. We hypothesized that soft-diet feeding during development reduced levels of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, resulting in lower synaptic densities in this region. Male pups of C57BL/6 mice were fed either a solid (hard-diet group) or powdered diet (soft-diet group), starting at weaning. Expression of BDNF protein in the hippocampus and cerebral cortex was evaluated quantitatively with enzyme-linked immunosorbent assay (ELISA) at 1, 3 and 6 months of age. Reduction in BDNF protein levels due to soft diet was detected markedly in the hippocampus of 3- and 6-month-old mice. On the other hand, a soft diet showed no significant effect on BDNF content in the cerebral cortex throughout the ages investigated. Immunohistochemistry of hippocampal formation in 3-month-old mice revealed that intensities of BDNF immunoreactivity in the dentate gyrus granule cell layer and CA1 and CA3 pyramidal cell layers appeared diminished in mice fed the soft diet compared with mice fed the hard diet. These results indicate that insufficient mastication activity during development reduces BDNF protein levels in the hippocampus and influences synaptic plasticity in this region.

  9. Beta-adrenergic receptors are differentially expressed in distinct interneuron subtypes in the rat hippocampus.

    Science.gov (United States)

    Cox, David J; Racca, Claudia; LeBeau, Fiona E N

    2008-08-20

    Noradrenaline (NA) acting via beta-adrenergic receptors (betaARs) plays an important role in the modulation of memory in the hippocampus. betaARs have been shown to be expressed in principal cells, but their distribution across different interneuron classes is unknown. We have used specific interneuron markers including calcium binding proteins (parvalbumin, calbindin, and calretinin) and neuropeptides (somatostatin, neuropeptide Y, and cholecystokinin) together with either beta1AR or beta2AR to determine the distribution of these receptors in all major subfields of the hippocampus. We found that beta1AR-expressing interneurons were more prevalent in the CA3 and CA1 regions of the hippocampus than in the dentate gyrus, where they were relatively sparse. beta2AR-expressing interneurons were more uniformly distributed between all three regions of the hippocampus. A high proportion of neuropeptide Y-containing interneurons in the dentate gyrus co-expressed beta2AR. beta1AR labeling was common in interneurons expressing somatostatin and parvalbumin in the CA3 and CA1 regions, particularly in the stratum oriens of these regions. beta2AR labeling was more likely to be found than beta1AR labeling in cholecystokinin-expressing interneurons. In contrast, calretinin-containing interneurons were virtually devoid of beta1AR or beta2AR labeling. These regional and interneuron type-specific differences suggest functionally distinct roles for NA in modulating hippocampal activity via activation of betaARs.

  10. Kindling-Induced Changes in Plasticity of the Rat Amygdala and Hippocampus

    Science.gov (United States)

    Schubert, Manja; Siegmund, Herbert; Pape, Hans-Christian; Albrecht, Doris

    2005-01-01

    Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar…

  11. Upregulation of voltage-activated potassium channels in hippocampus of Aβ25.35-treated rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-liangWANG; Ya-pingPAN

    2004-01-01

    AIM: Potassium channels dysfunction has been indicated in Alzheimer disease. In the present study, the mRNA and protein expression alterations and the functional changes ot VOltage- activated potassium channels were studied in rat hippocampus after a single intracerebro- ventricular injection of β-amyloid peptide 25-35 (Aβ25.35). METHODS: The expressions of mRNA

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

    Institute of Scientific and Technical Information of China (English)

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

    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 shamoperated 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.

  13. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Ishii M

    2004-06-01

    Full Text Available The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

  14. The role of the hippocampus in flexible cognition and social behavior

    Directory of Open Access Journals (Sweden)

    Rachael D Rubin

    2014-09-01

    Full Text Available Successful behavior requires actively acquiring and representing information about the environment and people, and manipulating and using those acquired representations flexibly to optimally act in and on the world. The frontal lobes have figured prominently in most accounts of flexible or goal-directed behavior, as evidenced by often-reported behavioral inflexibility in individuals with frontal lobe dysfunction. Here, we propose that the hippocampus also plays a critical role by forming and reconstructing relational memory representations that underlie flexible cognition and social behavior. There is mounting evidence that damage to the hippocampus can produce inflexible and maladaptive behavior when such behavior places high demands on the generation, recombination, and flexible use of information. This is seen in abilities as diverse as memory, navigation, exploration, imagination, creativity, decision-making, character judgments, establishing and maintaining social bonds, empathy, social discourse, and language use. Thus, the hippocampus, together with its extensive interconnections with other neural systems, supports the flexible use of information in general. Further, we suggest that this understanding has important clinical implications. Hippocampal abnormalities can produce profound deficits in real-world situations, which typically place high demands on the flexible use of information, but are not always obvious on diagnostic tools tuned to frontal lobe function. This review documents the role of the hippocampus in supporting flexible representations and aims to expand our understanding of the dynamic networks that operate as we move through and create meaning of our world.

  15. 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, was...

  16. Parvalbumin-Positive Neurons in Rat Dorsal Hippocampus Contain Muscarinic Acetylcholine Receptors

    NARCIS (Netherlands)

    Zee, E.A. van der; de Jong, Giena; Strosberg, A.D.; Luiten, P.G.M.

    1991-01-01

    The present study describes the colocalization of muscarinic acetylcholine receptors (mAChRs) and the calcium-binding protein parvalbumin (PARV) in nonpyramidal neurons of the rat dorsal hippocampus by means of dual-label immunocytochemistry. Fifty-two percent of all muscarinic cholinoceptive

  17. Hippocampus and two-way active avoidance conditioning: Contrasting effects of cytotoxic lesion and temporary inactivation.

    Science.gov (United States)

    Wang, Jia; Bast, Tobias; Wang, Yu-Cong; Zhang, Wei-Ning

    2015-12-01

    Hippocampal lesions tend to facilitate two-way active avoidance (2WAA) conditioning, where rats learn to cross to the opposite side of a conditioning chamber to avoid a tone-signaled footshock. This classical finding has been suggested to reflect that hippocampus-dependent place/context memory inhibits 2WAA (a crossing response to the opposite side is inhibited by the memory that this is the place where a shock was received on the previous trial). However, more recent research suggests other aspects of hippocampal function that may support 2WAA learning. More specifically, the ventral hippocampus has been shown to contribute to behavioral responses to aversive stimuli and to positively modulate the meso-accumbens dopamine system, whose activation has been implicated in 2WAA learning. Permanent hippocampal lesions may not reveal these contributions because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesion-induced extra-hippocampal changes, including an upregulation of accumbal dopamine transmission. Here, we re-examined the hippocampal role in 2WAA learning in Wistar rats, using permanent NMDA-induced neurotoxic lesions and temporary functional inhibition by muscimol or tetrodotoxin (TTX) infusion. Complete hippocampal lesions tended to facilitate 2WAA learning, whereas ventral (VH) or dorsal hippocampal (DH) lesions had no effect. In contrast, VH or DH muscimol or TTX infusions impaired 2WAA learning. Ventral infusions caused an immediate impairment, whereas after dorsal infusions rats showed intact 2WAA learning for 40-50 min, before a marked deficit emerged. These data show that functional inhibition of ventral hippocampus disrupts 2WAA learning, while the delayed impairment following dorsal infusions may reflect the time required for drug diffusion to ventral hippocampus. Overall, using temporary functional inhibition, our study shows that the ventral

  18. Learning-facilitated synaptic plasticity occurs in the intermediate hippocampus in association with spatial learning

    Science.gov (United States)

    Kenney, Jana; Manahan-Vaughan, Denise

    2013-01-01

    The dorsoventral axis of the hippocampus is differentiated into dorsal, intermediate, and ventral parts. Whereas the dorsal part is believed to specialize in processing spatial information, the ventral may be equipped to process non-spatial information. The precise role of the intermediate hippocampus is unclear, although recent data suggests it is functionally distinct, at least from the dorsal hippocampus. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with robust synaptic plasticity (>24 h) when a spatial learning event is coupled with afferent stimulation that would normally not lead to a lasting plasticity response: in the dorsal hippocampus novel space facilitates robust expression of long-term potentiation (LTP), whereas novel spatial content facilitates long-term depression (LTD). We explored whether the intermediate hippocampus engages in this kind of synaptic plasticity in response to novel spatial experience. In freely moving rats, high-frequency stimulation at 200 Hz (3 bursts of 15 stimuli) elicited synaptic potentiation that lasted for at least 4 h. Coupling of this stimulation with the exploration of a novel holeboard resulted in LTP that lasted for over 24 h. Low frequency afferent stimulation (1 Hz, 900 pulses) resulted in short-term depression (STD) that was significantly enhanced and prolonged by exposure to a novel large orientational (landmark) cues, however LTD was not enabled. Exposure to a holeboard that included novel objects in the holeboard holes elicited a transient enhancement of STD of the population spike (PS) but not field EPSP, and also failed to facilitate the expression of LTD. Our data suggest that the intermediate dentate gyrus engages in processing of spatial information, but is functionally distinct to the dorsal dentate gyrus. This may in turn reflect their assumed different roles in synaptic information processing and memory formation. PMID:24194716

  19. The roles of the medial prefrontal cortex and hippocampus in a spatial paired-association task.

    Science.gov (United States)

    Lee, Inah; Solivan, Frances

    2008-05-01

    Although the roles of both the hippocampus and the medial prefrontal cortex (mPFC) have been suggested in a spatial paired-associate memory task, both areas were investigated separately in prior studies. The current study investigated the relative contributions of the hippocampus and mPFC to spatial paired-associate learning within a single behavioral paradigm. In a novel behavioral task, a pair of different objects appeared repeatedly across trials, but in different arms in a radial maze, and different rules were associated with those arms for reward. Specifically, in an "object-in-place" arm, the rat was required to choose a particular object associated with the arm. In a "location-in-place" arm, the animal was required to choose a certain within-arm location (ignoring the object occupying the location). Compared to normal animals, rats with ibotenic acid-based lesions in the hippocampus showed an irrecoverable impairment in performance in both object-in-place and location-in-place arms. When the mPFC was inactivated by muscimol (GABA(A) receptor agonist) in the normal animals with intact hippocampi, they showed the same severe impairment as seen in the hippocampal lesioned rats only in object-in-place arms. The results confirm that the hippocampus is necessary for a biconditional paired-associate task when space is a critical component. The mPFC, however, is more selectively involved in the object-place paired-associate task than in the location-place paired-associate task. The current task powerfully demonstrates an experimental situation in which both the hippocampus and mPFC are required and may serve as a useful paradigm for investigating the neural mechanisms of object-place association.

  20. Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases

    Directory of Open Access Journals (Sweden)

    Ulises Gomez-Pinedo

    2016-11-01

    Full Text Available Background: Several findings suggest that the amyloid precursor protein (APP and the amyloid cascade may play a role in motor neuron disease (MND.Objective: Considering that dementia is one of the most frequently non-motor symptoms in ALS and that hippocampus is one of the brain areas with greater presence of amyloid related changes in neurodegenerative diseases, our aim was to analyse the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-FTD.Methods: We included 9 patients with MND and 4 controls. Immunohistochemical studies and confocal microscopy were used to analyse the expression of APP, TDP-43, pho-TDP-43, Aβ, AICD peptide, Fe65 protein, and pho-TAU in the hippocampus of 7 patients with ALS, 2 patients with ALS-FTD, and 4 controls. These findings were correlated with clinical data.Results: Patients displayed increased expression of APP and Aβ peptide. The latter was correlated with cytoplasmic pho-TDP-43 expression. We also found decreased Fe65 expression. A parallel increase in AICD expression was not found. Patients showed increased expression of pho-TAU in the hippocampus. Findings were similar in patients with ALS and those with ALS-FTD, though more marked in the latter group.Conclusion: Post-mortem analyses showed that the amyloid cascade is activated in the hippocampus of patients with MND and correlated with cytoplasmic pho-TDP-43 expression. The number of intra- or extracellular aggregates of Aβ peptides was not significant.

  1. Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

    2017-09-01

    Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The amygdala modulates neuronal activation in the hippocampus in response to spatial novelty.

    Science.gov (United States)

    Sheth, Archana; Berretta, Sabina; Lange, Nicholas; Eichenbaum, Howard

    2008-01-01

    Emerging evidence indicates that the amygdala and the hippocampus play an important role in the pathophysiology of major psychotic disorders. Consistent with this evidence, and with data indicating amygdala modulation of hippocampal activity, animal model investigations have shown that a disruption of amygdala activity induces neurochemical changes in the hippocampus that are similar to those detected in subjects with schizophrenia. With the present study, we used induction of the immediate early gene Fos, to test the hypothesis that the amygdala may affect neuronal activation of the hippocampus in response to different spatial environments (familiar, modified, and novel). Exploratory and anxiety related behaviors were also assessed. In vehicle-treated rats, exposure to a modified version of the familiar environment was associated with an increase of numerical densities of Fos-immunoreactive nuclei in sectors CA1 and CA2, while exposure to a completely novel environment was associated with an increase in sectors CA1, CA4, and DG, compared with the familiar environment. Pharmacological disruption of amygdala activity resulted in a failure to increase Fos induction in the hippocampus in response to these environments. Exploratory behavior in response to the different environments was not altered by manipulation of amygdala activity. These findings support the idea that the amygdala modulates spatial information processing in the hippocampus and may affect encoding of specific environmental features, while complex behavioral responses to environment may be the result of broader neural circuits. These findings also raise the possibility that amygdala abnormalities may contribute to impairments in cognitive information processing in subjects with major psychoses.

  3. Early life stress perturbs the maturation of microglia in the developing hippocampus.

    Science.gov (United States)

    Delpech, Jean-Christophe; Wei, Lan; Hao, Jin; Yu, Xiaoqing; Madore, Charlotte; Butovsky, Oleg; Kaffman, Arie

    2016-10-01

    Children exposed to abuse or neglect show abnormal hippocampal development and similar findings have been reported in rodent models. Using brief daily separation (BDS), a mouse model of early life stress, we previously showed that exposure to BDS impairs hippocampal function in adulthood and perturbs synaptic maturation, synaptic pruning, axonal growth and myelination in the developing hippocampus. Given that microglia are involved in these developmental processes, we tested whether BDS impairs microglial activity in the hippocampus of 14 (during BDS) and 28-day old mice (one week after BDS). We found that BDS increased the density and altered the morphology of microglia in the hippocampus of 14-day old pups, effects that were no longer present on postnatal day (PND) 28. Despite the normal cell number and morphology seen at PND28, the molecular signature of hippocampal microglia, assessed using the NanoString immune panel, was altered at both ages. We showed that during normal hippocampal development, microglia undergo significant changes between PND14 and PND28, including reduced cell density, decreased ex vivo phagocytic activity, and an increase in the expression of genes involved in inflammation and cell migration. However, microglia harvested from the hippocampus of 28-day old BDS mice showed an increase in phagocytic activity and reduced expression of genes that normally increase across development. Promoter analysis indicated that alteration in the transcriptional activity of PU.1, Creb1, Sp1, and RelA accounted for most of the transcriptional changes seen during normal microglia development and for most of the BDS-induced changes at PND14 and PND28. These findings are the first to demonstrate that early life stress dysregulates microglial function in the developing hippocampus and to identify key transcription factors that are likely to mediate these changes.

  4. Hippocampus's role in forming "task-related" associations: Flashing to the things you are looking for

    Institute of Scientific and Technical Information of China (English)

    ZHANG XiuLing; NIKI Kazuhisa; LUO Jing

    2008-01-01

    Eichenbaum and colleagues observed that the same place did or did not activate the "goal-approach" cells in hippocampus depending on whether the place was the way for rata to approach specific goal.Parallel with this,the present neuroimage study revealed that,the same type of items could activate the hippocampus more when it was related to the task at hand than when it not.Participants were scanned by fMRI while they made judgments on the type of relationships contained in the word-pairs (e.g.,Does the word pair,"furniture-table",contain a "category-exemplar" relationship?).Event-related analysis revealed that the forming of "task-related" association activated hippocampus more than that of "task-unrelated",even if it was the same type of items,and,this hippocampsl difference was not caused by the different judgment requirements,nor by the effects of "yes" response.Consistently,the post-judgment cued-recall test exhibited a better retrieval performance for "task-related" associations than for the same type but "task-unrelated" associations.Results also showed that,the semantic re-latedness between the to-be-associated individual words (e.g.,the related word pair "healthy-hospital"versus the unrelated word pair "price-way") was not enough to activate the hippocampus when it was"task-unrelated".Generally,we proposed that,through participating in forming of "task-related" asso-ciations and consolidating of episodic memory,hippocampus enabled the organism to keep the in-formation that owned great survival values in mind for future usage.

  5. Alzheimer's disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla).

    Science.gov (United States)

    Perez, Sylvia E; Raghanti, Mary Ann; Hof, Patrick R; Kramer, Lynn; Ikonomovic, Milos D; Lacor, Pascale N; Erwin, Joseph M; Sherwood, Chet C; Mufson, Elliott J

    2013-12-15

    The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (Aβ) plaques and neurofibrillary tangles (NFT). Aβ pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD-related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined Aβ and tau-like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age-related increase in Aβ-immunoreactive plaques and vasculature in the gorilla brain. Aβ plaques were more abundant in the neocortex and hippocampus of females, whereas Aβ-positive blood vessels were more widespread in male gorillas. Plaques were also Aβ40-, Aβ42-, and Aβ oligomer-immunoreactive, but only weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less fibrillar (diffuse) nature of Aβ plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both Aβ plaques and tau-like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research.

  6. Learning-facilitated synaptic plasticity occurs in the intermediate hippocampus in association with spatial learning

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    Jana eKenney

    2013-10-01

    Full Text Available The dorsoventral axis of the hippocampus is differentiated into dorsal, intermediate and ventral parts. Whereas the dorsal part is believed to specialize in processing spatial information, the ventral may be equipped to process non-spatial information. The precise role of the intermediate hippocampus is unclear, although recent data suggests it is functionally distinct, at least from the dorsal hippocampus. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with robust synaptic plasticity (>24h when a spatial learning event is coupled with afferent stimulation that would normally not lead to a lasting plasticity response: In the dorsal hippocampus novel space facilitates robust expression of LTP, whereas novel spatial content facilitates LTD. We explored whether the intermediate hippocampus engages in this kind of synaptic plasticity in response to novel spatial experience.In freely moving rats, high-frequency stimulation at 200Hz (3 bursts of 15 stimuli elicited synaptic potentiation that lasted for at least 4h. Coupling of this stimulation with the exploration of a novel holeboard resulted in long-term potentiation (LTP that lasted for over 24h. Low frequency afferent stimulation (1Hz, 900 pulses resulted in short-term depression (STD that was significantly enhanced and prolonged by exposure to a novel large orientational (landmark cues, however LTD was not enabled. Exposure to a holeboard that included novel objects in the holeboard holes elicited a transient enhancement of STD of the population spike but not field EPSP, and also failed to facilitate the expression of LTD. Our data suggest that the intermediate dentate gyrus engages in processing of spatial information, but is functionally distinct to the dorsal dentate gyrus. This may in turn reflect their assumed different roles in synaptic information processing and memory formation.

  7. Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells (NPCs) from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro.Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis.Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-βIII-tubulin (Tuj1) and 84% expressed astrocyte specific marker-fibrillary acidic protein (GFAP). In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

  8. Corresponding erdosteine changes autophagy genes expression in hippocampus on Rhinitis medicamentosa model

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    Dokuyucu Recep

    2015-01-01

    Full Text Available In our study, rats were subjected to Oxymetazoline hydrochloride treatment and Rhinitis medicamentosa (RM was formed and then autophagy gene expression levels were determined after the application of an antioxidant agent erdosteine (ED. The rats were divided into three groups; Group 1 was the control group. Group 2 (RM and group 3 (RM+ED rats received two spray puffs of 0.05% oxymetazoline into the nasal cavities three times daily for eight weeks. After determination of RM in the rats, the RM group were killed. The ED+RM group received 10 mg/kg of an ED suspension. At the end of seven days, these rats were also killed. All groups’ hippocampus tissues were obtained for the measurement of autophagy gene expressions. In rhinitis medicamentosa group Atg5, Atg7 and Atg10 gene expressions in the left hippocampus were reduced as compared to control group (p=0.01, p>0.05, p=0.01, respectively. Also, erdosteine treatments were restored mRNA expression of autophagy genes. In right hippocampus of rhinitis medicamentosa group, Atg5 and Atg10 gene expressions was found to be down-regulated as compared to control group (p>0.05, p<0.05, respectively. Both BECN1 and ULK genes expression were found to be reduced in left hippocampus of rhinitis medicamentosa group. Erdosteine applications was restored the expression of these genes (p=0.03, p=0.03, respectively. Additionally, in right hippocampus, Erdosteine application was restored the expression of ULK gene (p=0.01. This is the first report that evaluated the expression autophagy genes in RM rat models and the changes observed after erdosteine applications.

  9. Search-related suppression of hippocampus and default network activity during associative memory retrieval

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    Emilie T Reas

    2011-10-01

    Full Text Available Episodic memory retrieval involves the coordinated interaction of several cognitive processing stages such as mental search, access to a memory store, associative re-encoding and post-retrieval monitoring. The neural response during memory retrieval is an integration of signals from multiple regions that may subserve supportive cognitive control, attention, sensory association, encoding or working memory functions. It is particularly challenging to dissociate contributions of these distinct components to brain responses in regions such as the hippocampus, which lies at the interface between overlapping memory encoding and retrieval, and default networks. In the present study, event-related functional magnetic resonance imaging and measures of memory performance were used to differentiate brain responses to memory search from sub-components of episodic memory retrieval associated with successful recall. During the attempted retrieval of both poorly and strongly remembered word pair associates, the hemodynamic response was negatively deflected below baseline in anterior hippocampus and regions of the default network. Activations in anterior hippocampus were functionally distinct from those in posterior hippocampus and negatively correlated with response times. Thus, relative to the pre-stimulus period, the hippocampus shows reduced activity during intensive engagement in episodic memory search. Such deactivation was most salient during trials that engaged only pre-retrieval search processes in the absence of successful recollection or post-retrieval processing. Implications for interpretation of hippocampal fMRI responses during retrieval are discussed. A model is presented to interpret such activations as representing modulation of encoding-related activity, rather than retrieval-related activity. Engagement in intensive mental search may reduce neural and attentional resources that are otherwise tonically devoted to encoding an individual

  10. Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus.

    Science.gov (United States)

    Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza

    2014-07-01

    Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.

  11. Microglial activation in the hippocampus of hypercholesterolemic rabbits occurs independent of increased amyloid production

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    Streit Wolfgang J

    2007-08-01

    Full Text Available Abstract Background Rabbits maintained on high-cholesterol diets are known to show increased immunoreactivity for amyloid beta protein in cortex and hippocampus, an effect that is amplified by presence of copper in the drinking water. Hypercholesterolemic rabbits also develop sporadic neuroinflammatory changes. The purpose of this study was to survey microglial activation in rabbits fed cholesterol in the presence or absence of copper or other metal ions, such as zinc and aluminum. Methods Vibratome sections of the rabbit hippocampus and overlying cerebral cortex were examined for microglial activation using histochemistry with isolectin B4 from Griffonia simplicifolia. Animals were scored as showing either focal or diffuse microglial activation with or without presence of rod cells. Results Approximately one quarter of all rabbits fed high-cholesterol diets showed evidence of microglial activation, which was always present in the hippocampus and not in the cortex. Microglial activation was not correlated spatially with increased amyloid immunoreactivity or with neurodegenerative changes and was most pronounced in hypercholesterolemic animals whose drinking water had been supplemented with either copper or zinc. Controls maintained on normal chow were largely devoid of neuroinflammatory changes, but revealed minimal microglial activation in one case. Conclusion Because the increase in intraneuronal amyloid immunoreactivity that results from administration of cholesterol occurs in both cerebral cortex and hippocampus, we deduce that the microglial activation reported here, which is limited to the hippocampus, occurs independent of amyloid accumulation. Furthermore, since neuroinflammation occurred in the absence of detectable neurodegenerative changes, and was also not accompanied by increased astrogliosis, we conclude that microglial activation occurs because of metabolic or biochemical derangements that are influenced by dietary factors.

  12. The developmental trajectory of hippocampus across the human lifespan based on multimodal neuroimaging

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    Xiu WANG

    2014-04-01

    Full Text Available Background During the last 2 decades, more and more functional MRI (fMRI researches have increasingly focused on both structures and functions of the hippocampal region to discover the relationship between hippocampus and memory. In order to reveal the normative pattern of individual development or aging processes of the hippocampus or further memory-related disease prediction, an investigation on such a brain structure's trajectory across the human lifespan is necessary.  Methods Regional volume is the most commonly used variable for the structural change of normal brain. The regional homogeneity (ReHo and amplitude of low-frequency fluctuation (ALFF are the two test-retest reliable metrics for detection of functional changes. We here investigate ReHo, ALFF and fractional ALFF (fALFF based upon both structural and resting state fMRI of 125 subjects from 7 to 85 years old.  Results As results, significant age-related decreases were detected for volumes of bilateral hippocampus (corrected Ps = 0.000. In contrast, ALFF (corrected P = 0.034, β = -0.314, fALFF (corrected P = 0.059, β = - 0.687 and ReHo (corrected P = 0.005, β = - 0.330 demonstrated a trend of negative linear correlation with age in the left hippocampus.  Conclusions Our findings partly reflect the structure-function relationship of the hippocampus during the human lifespan. doi: 10.3969/j.issn.1672-6731.2014.04.006

  13. Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus

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    Chiang, Cheng-Kang; Xu, Bo; Mehta, Neel; Mayne, Janice; Sun, Warren Y. L.; Cheng, Kai; Ning, Zhibin; Dong, Jing; Zou, Hanfa; Cheng, Hai-Ying Mary; Figeys, Daniel

    2017-01-01

    The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription–translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short- to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of

  14. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones.

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    Benedetta Leuner

    Full Text Available Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute or once daily for 14 consecutive days (chronic and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated

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

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    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.

  16. Toxicological study of injuries of rat's hippocampus after lead poisoning by synchrotron microradiography and elemental mapping

    Energy Technology Data Exchange (ETDEWEB)

    Liang Feng [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhang Guilin, E-mail: glzhang@sinap.ac.c [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Xiao Xianghui; Cai Zhonghou; Lai, Barry [Advanced Photon Source, Argonne (United States); Hwu Yeukuang [Institute of Physics, Academia Sinica, Nankang, Taipei (China); Yan Chonghuai; Xu Jian [Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Children' s Environmental Health, Shanghai 200092 (China); Li Yulan; Tan Mingguang; Zhang Chuanfu [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Li Yan, E-mail: liyan@sinap.ac.c [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

    2010-09-15

    The hippocampus, a major component of the brain, is one of the target nervous organs in lead poisoning. In this work, a rat's hippocampal injury caused by lead was studied. The lead concentrations in blood, bone and hippocampus collected from rats subject to lead poisoning were quantified by Inductively Coupled Plasma Mass Spectrometry while morphological information and elemental distributions in the hippocampus were obtained with synchrotron radiation X-ray phase contrast imaging and synchrotron radiation micro-beam X-ray fluorescence, respectively. For comparison, identical characterization of the specimens from the rats in the control group was done in parallel. Results show that the ratios between the lead content in the treated group and that in the control group of the hippocampus, bone, and blood are about 2.66, 236, and 39.6, respectively. Analysis also revealed that some health elements such as S, K, Cl and P increase in the regions with high lead content in the treated hippocampus. Morphological differences between the normal and lead-exposed hippocampus specimens in some local areas were observed. Explicitly, the structure of the lead-exposed hippocampus was tortuous and irregular, and the density of the neurons in the Dentate Gyrus was significantly lower than that from the control group. The study shows that the synchrotron radiation methods are very powerful for investigating structural injury caused by heavy metals in the nervous system.

  17. Toxicological study of injuries of rat’s hippocampus after lead poisoning by synchrotron microradiography and elemental mapping

    Science.gov (United States)

    Liang, Feng; Zhang, Guilin; Xiao, Xianghui; Cai, Zhonghou; Lai, Barry; Hwu, Yeukuang; Yan, Chonghuai; Xu, Jian; Li, Yulan; Tan, Mingguang; Zhang, Chuanfu; Li, Yan

    2010-09-01

    The hippocampus, a major component of the brain, is one of the target nervous organs in lead poisoning. In this work, a rat's hippocampal injury caused by lead was studied. The lead concentrations in blood, bone and hippocampus collected from rats subject to lead poisoning were quantified by Inductively Coupled Plasma Mass Spectrometry while morphological information and elemental distributions in the hippocampus were obtained with synchrotron radiation X-ray phase contrast imaging and synchrotron radiation micro-beam X-ray fluorescence, respectively. For comparison, identical characterization of the specimens from the rats in the control group was done in parallel. Results show that the ratios between the lead content in the treated group and that in the control group of the hippocampus, bone, and blood are about 2.66, 236, and 39.6, respectively. Analysis also revealed that some health elements such as S, K, Cl and P increase in the regions with high lead content in the treated hippocampus. Morphological differences between the normal and lead-exposed hippocampus specimens in some local areas were observed. Explicitly, the structure of the lead-exposed hippocampus was tortuous and irregular, and the density of the neurons in the Dentate Gyrus was significantly lower than that from the control group. The study shows that the synchrotron radiation methods are very powerful for investigating structural injury caused by heavy metals in the nervous system.

  18. Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine.

    Science.gov (United States)

    Long, Lili; Xiao, Bo; Feng, Li; Yi, Fang; Li, Guoliang; Li, Shuyu; Mutasem, M Abuhamed; Chen, Si; Bi, Fangfang; Li, Yi

    2011-02-01

    In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.

  19. Distinct effect of stress on 11beta-hydroxysteroid dehydrogenase type 1 and corticosteroid receptors in dorsal and ventral hippocampus.

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    Ergang, P; Kuželová, A; Soták, M; Klusoňová, P; Makal, J; Pácha, J

    2014-01-01

    Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus-pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that regulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions.

  20. Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats.

    Science.gov (United States)

    Kim, Hong; Lee, Myoung-Hwa; Chang, Hyun-Kyung; Lee, Taeck-Hyun; Lee, Hee-Hyuk; Shin, Min-Chul; Shin, Mal-Soon; Won, Ran; Shin, Hye-Sook; Kim, Chang-Ju

    2006-03-01

    During the prenatal period, the development of individual is influenced by the environmental factors. In the present study, the influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats was investigated. The exposure to the noise during pregnancy caused growth retardation, decreased neurogenesis in the hippocampus, and impaired spatial learning ability in pups. The exposure to music during pregnancy, on the other hand, caused increased neurogenesis in the hippocampus and enhanced spatial learning ability in pups. The present study has shown the importance of the prenatal environmental conditions for the cognition and brain development.

  1. Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice

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    Karin eTein

    2015-08-01

    Full Text Available BackgroundMutations in WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder, characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness (DIDMOAD. The WFS1 gene product wolframin is located in the endoplasmic reticulum. Mice lacking this gene exhibit disturbances in the processing and secretion of peptides, such as vasopressin and insulin. In the brain, high levels of the wolframin protein have been observed in the hippocampus, amygdala and limbic structures. The aim of this study was to investigate the effect of Wfs1 knockout on peptide processing in mouse hippocampus. A peptidomic approach was used to characterize individual peptides in the hippocampus of wild-type and Wfs1 knockout mice. ResultsWe identified 126 peptides in hippocampal extracts and the levels of 10 peptides differed between Wfs1 KO and wild-type mice at P<0.05. The peptide with the largest alteration was little-LEN, which level was 25 times higher in the hippocampus of Wfs1 KO mice compared to wild-type mice. Processing (cleavage of little-LEN from the Pcsk1n gene product proSAAS involves prohormone convertase 2 (PC2. Thus, PC2 activity was measured in extracts prepared from the hippocampus of Wfs1 knockout mice. The activity of PC2 in Wfs1 mutant mice was significantly higher (149.9±2.3%, p<0.0001, n=8 than in wild-type mice (100.0±7.0%, n=8. However, Western blot analysis showed that protein levels of 7B2, proPC2 and PC2 were same in both groups, and so were gene expression levels.ConclusionsProcessing of proSAAS is altered in the hippocampus of Wfs1-KO mice, which is caused by increased activity of PC2. Increased activity of PC2 in Wfs1 knockout mice is not caused by alteration in the levels of PC2 protein. Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation.

  2. DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.

    Science.gov (United States)

    GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreact...

  3. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C. M. ('Benno'); Burger, Huibert; Doorduin, Janine; Renken, Remco J.; Sibeijn-Kuiper, Anita J.; Marsman, Jan-Bernard C.; de Vries, Erik F. J.; de Groot, Jan Cees; Drexhage, Hemmo A.; Mendes, Richard; Nolen, Willem A.; Riemersma-Van der Lek, Rixt F.

    2016-01-01

    Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipola

  4. Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats.

    Science.gov (United States)

    Selvakumar, Kandaswamy; Bavithra, Senthamilselvan; Suganthi, Muralidharan; Benson, Chellakan Selvanesan; Elumalai, Perumal; Arunkumar, Ramachandran; Krishnamoorthy, Gunasekaran; Venkataraman, Prabhu; Arunakaran, Jagadeesan

    2012-04-01

    Polychlorinated biphenyls (PCBs) exposure produces neurodegeneration and induces oxidative stress. Neuroprotective role of quercetin, on PCBs induced apoptosis in hippocampus has not yet been studied. The present study is focused to see whether quercetin supplementation precludes against PCBs induced oxidative stress and hippocampal apoptosis. The results have shown that quercetin at 50 mg/kg bwt/30 days has protected oxidative stress in hippocampus of adult male rats. Quercetin, a free radical scavenger decreased the levels of oxidative stress markers in the hippocampus of simultaneous PCB+quercetin treated rats. The pro-apoptotic and anti-apoptotic molecules such as Bad, Bid, Bax and Bcl2 were altered in the hippocampus of experimental animals. PCBs increased the DNA damage and induced neurodegeneration were assessed by histological studies. PCB induced ROS may be linked to increased hippocampal neuronal apoptosis. Quercetin supplementation decreased the neuronal damage and scavenged the free radicals induced by PCBs and protects PCBs induced apoptosis and oxidative stress.

  5. Effects of visual deprivation during brain development on expression of AMPA receptor subunits in rat’s hippocampus

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    Sayyed Alireza Talaei

    2015-06-01

    Conclusion: Dark rearing of rats during critical period of brain development changes the relative expression and also arrangement of both AMPA receptor subunits, GluR1 and GluR2 in the hippocampus, age dependently.

  6. 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.

  7. Effect of phenylsuccinate on potassium- and ischemia-induced release of glutamate in rat hippocampus monitored by microdialysis

    DEFF Research Database (Denmark)

    Christensen, Thomas; Bruhn, T; Diemer, Nils Henrik

    1991-01-01

    The extracellular concentration of glutamate in rat hippocampus during physiological conditions, elevated extracellular K+ and global ischemia was followed by microdialysis and subsequent determination of glutamate by HPLC. The effect of phenylsuccinate, an inhibitor of the mitochondrial dicarbox...

  8. Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

    Science.gov (United States)

    Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

    2011-01-01

    In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

  9. Upregulation of Mark3 and Rpgrip1 mRNA expression by jujuboside A in mouse hippocampus

    Institute of Scientific and Technical Information of China (English)

    Cheng WANG; Zi-li YOU; Qing XIA; Tao XIONG; Yang XIA; De-zhong YAO

    2007-01-01

    Aim: To investigate the effect ofjujuboside A (JuA) on modulating gene expres-sion in the hippocampus. Methods: The spontaneous activity of mice was monitored, and the differential display polymerase chain reaction was adapted to screen differentially-expressed genes modulated by JuA in the mouse hippocampus.Results: JuA significantly decreased the total activity intensity (P<0.01 vs control) at a dosage of 80 mg/kg, and the genes MAP/microtubule affinity-regulating kinase3 (Mark3) and retinitis pigmentosa GTPase regulator interacting proteinl(Rpgripl) were upregulated by JuA in the mouse hippocampus. Conclusion: JuA had an inhibitory effect on the spontaneous activity of the mice, and JuA regu-lated the transcription of Mark3 and Rpgripl in the mouse hippocampus.

  10. Effect of [Ca2+]i and Neuronal Mitochondria Transmembrane Potentials in Hippocampus of Murine Cytomegalovirus Infected Mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; WEN Liangzhen; CHENG Biheng

    2006-01-01

    To explore the effect of [Ca2+]I and neuronal mitochondria transmembrane potentials in hippocampus of murine cytomegalovirus (MCMV) infected mice, newborn Balb/c mice were randomly divided into two groups: a virus inoculated group and a control group. After 56 days, single cell of hippocampus was isolated, and mitochondria transmembrane potentials and the intracellular free calcium level [Ca2+ ]I in hippocampus were measured by means of flow cytometry (FCM).Compared with the control group, the mitochondria transmembrane potentials was decreased (P<0.01) and the intracellular free calcium level [Ca2+]I was increased (P<0.01) in inoculated group.The dysfunction of [Ca2+ ]I and mitochondria transmembrane potentials in hippocampus may play an important role in the functional disorders in CMV-infected CNS.

  11. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C M 'Benno'; Burger, Huibert; Doorduin, Janine; Renken, Remco J; Sibeijn-Kuiper, Anita J; Marsman, Jan-Bernard C.; de Vries, Erik; de Groot, Jan Cees; Drexhage, Hemmo A; Mendes, Richard; Nolen, Willem A; Riemersma-Van der Lek, Rixt F

    2016-01-01

    BACKGROUND: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipola

  12. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C. M. ('Benno'); Burger, Huibert; Doorduin, Janine; Renken, Remco J.; Sibeijn-Kuiper, Anita J.; Marsman, Jan-Bernard C.; Vries, de Erik; de Groot, Jan Cees; Drexhage, Hemmo A.; Mendes, Richard; Nolen, Willem A.; Riemersma-Van der Lek, Rixt F.

    2016-01-01

    Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipola

  13. Effects of combined prenatal stress and toluene exposure on apoptotic neurodegeneration in cerebellum and hippocampus of rats

    DEFF Research Database (Denmark)

    Ladefoged, Ole; Hougaard, Karin Sørig; Hass, Ulla

    2004-01-01

    the offspring for developmental neurotoxicity and level of apoptosis in the brain. The number of apoptotic cells in cerebellum postnatal day 22, 24, and 27 and in hippocampus (postnatal day 22, 24, and 27) were counted after visualization by the TUNEL staining or measured by DNA-laddering technique. Caspase-3...... activity was determined in cerebellum (postnatal day 6, 22, 24, and 27) and in hippocampus (postnatal day 6 and 22). TUNEL staining and DNA-laddering technique showed a marked decrease in number of apoptotic cells from postnatal day 22 to 27 in both cerebellum and hippocampus. Apparently, a peak...... in the number of TUNEL positive cells was identified in cerebellum at postnatal day 22. There was no statistically significant influence of exposure except that DNA-laddering in cerebellum at postnatal day 27 was increased by toluene exposure. Caspase-3 activity decreased in cerebellum and hippocampus with age...

  14. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injur y in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Wangxin Zhang; Qiuling Zhang; Wen Deng; Yalu Li; Guoqing Xing; Xianjun Shi; Yifeng Du

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-ti-oxidative and anti-inlfammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoder-ma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis fac-tor-αand interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. hTese results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-ti-inlfammatory actions.

  15. Oscillatory activity in the monkey hippocampus during visual exploration and memory formation.

    Science.gov (United States)

    Jutras, Michael J; Fries, Pascal; Buffalo, Elizabeth A

    2013-08-06

    Primates explore the visual world through the use of saccadic eye movements. Neuronal activity in the hippocampus, a structure known to be essential for memory, is modulated by this saccadic activity, but the relationship between visual exploration through saccades and memory formation is not well understood. Here, we identify a link between theta-band (3-12 Hz) oscillatory activity in the hippocampus and saccadic activity in monkeys performing a recognition memory task. As monkeys freely explored novel images, saccades produced a theta-band phase reset, and the reliability of this phase reset was predictive of subsequent recognition. In addition, enhanced theta-band power before stimulus onset predicted stronger stimulus encoding. Together, these data suggest that hippocampal theta-band oscillations act in concert with active exploration in the primate and possibly serve to establish the optimal conditions for stimulus encoding.

  16. Image-based adaptive optics for in vivo imaging in the hippocampus

    Science.gov (United States)

    Champelovier, D.; Teixeira, J.; Conan, J.-M.; Balla, N.; Mugnier, L. M.; Tressard, T.; Reichinnek, S.; Meimon, S.; Cossart, R.; Rigneault, H.; Monneret, S.; Malvache, A.

    2017-02-01

    Adaptive optics is a promising technique for the improvement of microscopy in tissues. A large palette of indirect and direct wavefront sensing methods has been proposed for in vivo imaging in experimental animal models. Application of most of these methods to complex samples suffers from either intrinsic and/or practical difficulties. Here we show a theoretically optimized wavefront correction method for inhomogeneously labeled biological samples. We demonstrate its performance at a depth of 200 μm in brain tissue within a sparsely labeled region such as the pyramidal cell layer of the hippocampus, with cells expressing GCamP6. This method is designed to be sample-independent thanks to an automatic axial locking on objects of interest through the use of an image-based metric that we designed. Using this method, we show an increase of in vivo imaging quality in the hippocampus.

  17. Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin.

    Science.gov (United States)

    Chen, Z L; Strickland, S

    1997-12-26

    Excess excitatory amino acids can provoke neuronal death in the hippocampus, and the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) have been implicated in this death. To investigate substrates for plasmin that might influence neuronal degeneration, extracellular matrix (ECM) protein expression was examined. Laminin is expressed in the hippocampus and disappears after excitotoxin injection. Laminin disappearance precedes neuronal death, is spatially coincident with regions that exhibit neuronal loss, and is blocked by either tPA-deficiency or infusion of a plasmin inhibitor, both of which also block neuronal degeneration. Preventing neuron-laminin interaction by infusion of anti-laminin antibodies into tPA-deficient mice restores excitotoxic sensitivity to their hippocampal neurons. These results indicate that disruption of neuron-ECM interaction via tPA/plasmin catalyzed degradation of laminin sensitizes hippocampal neurons to cell death.

  18. [Correlation of evoked potentials in the frontal cortex and hippocampus of cats in emotional stress].

    Science.gov (United States)

    Vanetsian, G L; Pavlova, I V

    2002-01-01

    Averaged auditory evoked potentials (AEPs) were recorded in symmetric points of the frontal cortex and dorsal hippocampus of cats performing acquired conditioned food-procuring reaction reinforced in 100% cases, urgent transition to 30%-reinforcement, and return to 100%-reinforcement. Emotional stress estimated by a heart rate rise developed during increased food motivation of a cat as well as during change in ordinary food-procuring stereotype. The emotional stress was accompanied by a high positive correlation of cortical and hippocampal AEPs. Decrease in the stress level led to a drop between AEP correlations and appearance of their negative values. In emotional stress, the interactions between the frontal cortex and dorsal hippocampus were asymmetric: right-side correlations were higher.

  19. Making new memories: the role of the hippocampus in new associative learning.

    Science.gov (United States)

    Suzuki, Wendy A

    2007-02-01

    Both aging and Alzheimer's disease target the hippocampal formation and can result in mild to devastating memory impairment depending on the severity of the condition. Understanding the normal mnemonic functions of the hippocampus and related structures of the medial temporal lobe is the first step toward the development of diagnostics and treatments designed to ameliorate these potentially devastating age-related memory deficits. Here I describe findings from behavioral neurophysiological studies in which we have investigated the patterns of dynamic neural activity seen in the macaque monkey hippocampus during the acquisition of new associative memories. We report that hippocampal neurons signal the formation of new associations with dramatic changes in their firing rate. Because these learning-related signals can occur just before behavioral learning is expressed, this suggests that these signals play a role in driving the learning process. Implications of these findings for understanding the memory deficits associated with aging and Alzheimer's disease are discussed.

  20. Hippocampus leads ventral striatum in replay of place-reward information.

    Directory of Open Access Journals (Sweden)

    Carien S Lansink

    2009-08-01

    Full Text Available Associating spatial locations with rewards is fundamental to survival in natural environments and requires the integrity of the hippocampus and ventral striatum. In joint multineuron recordings from these areas, hippocampal-striatal ensembles reactivated together during sleep. This process was especially strong in pairs in which the hippocampal cell processed spatial information and ventral striatal firing correlated to reward. Replay was dominated by cell pairs in which the hippocampal "place" cell fired preferentially before the striatal reward-related neuron. Our results suggest a plausible mechanism for consolidating place-reward associations and are consistent with a central tenet of consolidation theory, showing that the hippocampus leads reactivation in a projection area.

  1. TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.

    Science.gov (United States)

    Matsuda, Taito; Murao, Naoya; Katano, Yuki; Juliandi, Berry; Kohyama, Jun; Akira, Shizuo; Kawai, Taro; Nakashima, Kinichi

    2015-01-01

    Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity.

  2. Repeated stress increases catalytic TrkB mRNA in rat hippocampus.

    Science.gov (United States)

    Nibuya, M; Takahashi, M; Russell, D S; Duman, R S

    1999-05-28

    Northern blot analysis was utilized to distinguish between catalytic and truncated TrkB mRNA on the basis of transcript size. Repeated (10 days), but not acute, immobilization stress significantly increased levels of catalytic TrkB mRNA, but did not influence expression of truncated TrkB transcripts in rat hippocampus. Exposure to another paradigm, a combination of different, unpredictable stressors, also increased levels of catalytic, but not truncated, TrkB mRNA. In situ hybridization analysis demonstrated that chronic stress up-regulated TrkB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus. As previously reported, both acute and chronic immobilization stress decreased expression of BDNF mRNA, suggesting that up-regulation of catalytic TrkB mRNA may be a compensatory adaptation to repeated stress.

  3. Micro-RNA speciation in fetal, adult and Alzheimer's disease hippocampus.

    Science.gov (United States)

    Lukiw, Walter J

    2007-02-12

    Micro-RNAs constitute a family of small noncoding ribonucleic acids that are posttranscriptional regulators of messenger RNA activity. Although micro-RNAs are known to be dynamically regulated during neural development, the role of micro-RNAs in brain aging and neurodegeneration is not known. This study examined micro-RNA abundance in the hippocampal region of fetal, adult and Alzheimer's disease brain. The data indicate that micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain.

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

    Science.gov (United States)

    Weilbächer, Regina A.; Gluth, Sebastian

    2016-01-01

    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. PMID:28036071

  5. Simulation of Human Episodic Memory by Using a Computational Model of the Hippocampus

    Directory of Open Access Journals (Sweden)

    Naoyuki Sato

    2010-01-01

    Full Text Available The episodic memory, the memory of personal events and history, is essential for understanding the mechanism of human intelligence. Neuroscience evidence has shown that the hippocampus, a part of the limbic system, plays an important role in the encoding and the retrieval of the episodic memory. This paper reviews computational models of the hippocampus and introduces our own computational model of human episodic memory based on neural synchronization. Results from computer simulations demonstrate that our model provides advantage for instantaneous memory formation and selective retrieval enabling memory search. Moreover, this model was found to have the ability to predict human memory recall by integrating human eye movement data during encoding. The combined approach between computational models and experiment is efficient for theorizing the human episodic memory.

  6. Selective localization of Shanks to VGLUT1-positive excitatory synapses in the mouse hippocampus

    Directory of Open Access Journals (Sweden)

    Christopher eHeise

    2016-04-01

    Full Text Available AbstractMembers of the Shank family of multidomain proteins (Shank1, Shank2, and Shank3 are core components of the postsynaptic density (PSD of excitatory synapses. At synaptic sites Shanks serve as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin cytoskeleton. In this study we investigated the synapse specific localization of Shank1-3 and focused on well-defined synaptic contacts within the hippocampal formation. We found that all three family members are present only at VGLUT1-positive synapses, which is particularly visible at mossy fiber contacts. No costaining was found at VGLUT2-positive contacts indicating that the molecular organization of VGLUT2-associated PSDs diverges from classical VGLUT1-positive excitatory contacts in the hippocampus. In light of SHANK mutations in neuropsychiatric disorders, this study indicates which glutamatergic networks within the hippocampus will be primarily affected by shankopathies.

  7. Temporal and Rate Coding for Discrete Event Sequences in the Hippocampus.

    Science.gov (United States)

    Terada, Satoshi; Sakurai, Yoshio; Nakahara, Hiroyuki; Fujisawa, Shigeyoshi

    2017-06-21

    Although the hippocampus is critical to episodic memory, neuronal representations supporting this role, especially relating to nonspatial information, remain elusive. Here, we investigated rate and temporal coding of hippocampal CA1 neurons in rats performing a cue-combination task that requires the integration of sequentially provided sound and odor cues. The majority of CA1 neurons displayed sensory cue-, combination-, or choice-specific (simply, "event"-specific) elevated discharge activities, which were sustained throughout the event period. These event cells underwent transient theta phase precession at event onset, followed by sustained phase locking to the early theta phases. As a result of this unique single neuron behavior, the theta sequences of CA1 cell assemblies of the event sequences had discrete representations. These results help to update the conceptual framework for space encoding toward a more general model of episodic event representations in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Homing behavior of hippocampus and parahippocampus lesioned pigeons following short-distance releases.

    Science.gov (United States)

    Bingman, V P; Mench, J A

    1990-11-30

    The avian hippocampal formation has been proposed to play a critical role in the neural regulation of a navigational system used by homing pigeons to locate their loft once in the familiar area near home. In support of this hypothesis, the homing performance of pigeons with target lesions of either the hippocampus or parahippocampus was found to be impaired compared to controls following releases of about 10 km. Further, radio tracking revealed that the in-flight behavior of the hippocampal lesioned homing pigeons was characterized by numerous direction changes and generally poor orientation with respect to the home loft. The results identify a local navigational impairment on the part of the hippocampal lesioned pigeons in the vicinity of the loft where landmark cues are thought to be important. Additionally, target lesions of the hippocampus or parahippocampus were found to be similarly effective in causing homing deficits.

  9. rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1

    Science.gov (United States)

    Wu, Haiqin; Wang, Huqing; Zhang, Wenting; Wei, Xuanhui; Zhao, Jiaxin; Yan, Pu; Liu, Chao

    2015-01-01

    The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of erythropoietin (EPO) and to clarify whether recombinant human EPO (rhEPO) affects apoptosis in the aging rat hippocampus by upregulating Sirtuin 1 (SIRT1). In this study, a rat model of aging was established using D-galactose. Behavioral changes were monitored by the Morris water maze test. Using immunohistochemistry, we studied the expression of SIRT1, B-cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 associated X protein (Bax) expression, and apoptotic cells in the hippocampus of a rat model of aging in which rhEPO was intraperitoneally injected. The escape latency in rats from the EPO group shortened significantly; however, the number of platform passes increased significantly from that in the D-gal group (P anti-aging property of EPO. PMID:26261574

  10. Image-based adaptive optics for in vivo imaging in the hippocampus

    Science.gov (United States)

    Champelovier, D.; Teixeira, J.; Conan, J.-M.; Balla, N.; Mugnier, L. M.; Tressard, T.; Reichinnek, S.; Meimon, S.; Cossart, R.; Rigneault, H.; Monneret, S.; Malvache, A.

    2017-01-01

    Adaptive optics is a promising technique for the improvement of microscopy in tissues. A large palette of indirect and direct wavefront sensing methods has been proposed for in vivo imaging in experimental animal models. Application of most of these methods to complex samples suffers from either intrinsic and/or practical difficulties. Here we show a theoretically optimized wavefront correction method for inhomogeneously labeled biological samples. We demonstrate its performance at a depth of 200 μm in brain tissue within a sparsely labeled region such as the pyramidal cell layer of the hippocampus, with cells expressing GCamP6. This method is designed to be sample-independent thanks to an automatic axial locking on objects of interest through the use of an image-based metric that we designed. Using this method, we show an increase of in vivo imaging quality in the hippocampus. PMID:28220868

  11. Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus

    Directory of Open Access Journals (Sweden)

    Gayane Grigoryan

    2016-01-01

    Full Text Available Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp., based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation.

  12. Sensitization to the conditioned rewarding effects of morphine modulates gene expression in rat hippocampus.

    Science.gov (United States)

    Marie-Claire, Cynthia; Courtin, Cindie; Robert, Amelie; Gidrol, Xavier; Roques, Bernard P; Noble, Florence

    2007-02-01

    Opiates addiction is characterized by its long-term persistence. In order to study the enduring changes in long-term memory in hippocampus, a pivotal region for this process, we used suppression subtractive hybridization to compare hippocampal gene expression in morphine and saline-treated rats. Animals were subjected to an extended place preference paradigm consisting of four conditioning phases. Sensitization to the reinforcing effects of the drug occurred after three conditioning phases. After 25 days of treatment rats were euthanized and the complementary DNA (cDNA) from the hippocampus of morphine-dependent and saline-treated animals were then screened for differentially expressed cDNAs. The selected 177 clones were then subjected to a microarray procedure and 20 clones were found differentially regulated. The pattern of regulated genes suggests impairments in neurotransmitter release and the activation of neuroprotective pathways.

  13. Embryonic stem cell-derived neural progenitors transplanted to the hippocampus migrate on host vasculature

    Directory of Open Access Journals (Sweden)

    Chelsea M. Lassiter

    2016-05-01

    Full Text Available This study describes the migration of transplanted ESNPs either injected directly into the hippocampus of a mouse, seeded onto hippocampal slices, or under in vitro culture conditions. We show that transplanted mouse ESNPs associate with, and appear to migrate on the surface of the vasculature, and that human ESNPs also associate with blood vessels when seeded on hippocampal slices, and migrate towards BECs in vitro using a Boyden chamber assay. This initial adhesion to vessels is mediated, at least in part, via the integrin α6β1, as observed for SVZ neural progenitor cells. Our data are consistent with CXCL12, expressed by the astroglial-vasculature niche, playing an important role in the migration of transplanted neural progenitors within and outside of the hippocampus.

  14. Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats.

    Science.gov (United States)

    Maren, Stephen

    2008-10-01

    Pavlovian fear conditioning has become an important model for investigating the neural substrates of learning and memory in rats, mice and humans. The hippocampus and amygdala are widely believed to be essential for fear conditioning to contexts and discrete cues, respectively. Indeed, this parsing of function within the fear circuit has been used to leverage fear conditioning as a behavioral assay of hippocampal and amygdala function, particularly in transgenic mouse models. Recent work, however, blurs the anatomical segregation of cue and context conditioning and challenges the necessity for the hippocampus and amygdala in fear learning. Moreover, nonassociative factors may influence the performance of fear responses under a variety of conditions. Caution must therefore be exercised when using fear conditioning as a behavioral assay for hippocampal- and amygdala-dependent learning.

  15. Stereological method for objectively quantifying myelin sheaths in the rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Wei Lu; Shu Yang; Lin Chen; Xuan Qiu; Guohua Cheng; Yong Tang

    2011-01-01

    In the present study, tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats. Isotropic, uniform and random sections, 60 nm thick, were prepared by isector. Fifteen fields of view were randomly selected for each section and photographed using a transmission electron microscope. The mean internal and external diameters of the myelin sheaths were obtained by measuring the longest profile diameter perpendicular to its longest axis.The inner and outer perimeters of the myelin sheaths were estimated using the equidistant parallel test lines. The thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. These stereological methods should permit an unbiased quantitative assessment of changes in the myelin sheaths of myelinated fibers in the hippocampus.

  16. Structural synaptic plasticity in the hippocampus induced by spatial experience and its implications in information processing.

    Science.gov (United States)

    Carasatorre, M; Ramírez-Amaya, V; Díaz Cintra, S

    2016-10-01

    Long-lasting memory formation requires that groups of neurons processing new information develop the ability to reproduce the patterns of neural activity acquired by experience. Changes in synaptic efficiency let neurons organise to form ensembles that repeat certain activity patterns again and again. Among other changes in synaptic plasticity, structural modifications tend to be long-lasting which suggests that they underlie long-term memory. There is a large body of evidence supporting that experience promotes changes in the synaptic structure, particularly in the hippocampus. Structural changes to the hippocampus may be functionally implicated in stabilising acquired memories and encoding new information. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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.

  18. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep.

    Science.gov (United States)

    Staresina, Bernhard P; Bergmann, Til Ole; Bonnefond, Mathilde; van der Meij, Roemer; Jensen, Ole; Deuker, Lorena; Elger, Christian E; Axmacher, Nikolai; Fell, Juergen

    2015-11-01

    During systems-level consolidation, mnemonic representations initially reliant on the hippocampus are thought to migrate to neocortical sites for more permanent storage, with an eminent role of sleep for facilitating this information transfer. Mechanistically, consolidation processes have been hypothesized to rely on systematic interactions between the three cardinal neuronal oscillations characterizing non-rapid eye movement (NREM) sleep. Under global control of de- and hyperpolarizing slow oscillations (SOs), sleep spindles may cluster hippocampal ripples for a precisely timed transfer of local information to the neocortex. We used direct intracranial electroencephalogram recordings from human epilepsy patients during natural sleep to test the assumption that SOs, spindles and ripples are functionally coupled in the hippocampus. Employing cross-frequency phase-amplitude coupling analyses, we found that spindles were modulated by the up-state of SOs. Notably, spindles were found to in turn cluster ripples in their troughs, providing fine-tuned temporal frames for the hypothesized transfer of hippocampal memory traces.

  19. Neurochemical phenotype of cytoglobin‑expressing neurons in the rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-01-01

    in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number...... of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic...... structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population...

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

    Energy Technology Data Exchange (ETDEWEB)

    Hoshida, Tohru; Sakaki, Toshisuke [Nara Medical Univ., Kashihara (Japan); Uematsu, Sumio

    1995-03-01

    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.).

  1. 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

    2013-12-01

    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 on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that 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.

  2. Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

    Science.gov (United States)

    Donahue, Christine P.; Jensen, Roderick V.; Ochiishi, Tomoyo; Eisenstein, Ingrid; Zhao, Mingrui; Shors, Tracey; Kosik, Kenneth S.

    2002-01-01

    Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

  3. Comment on "Multiple repressive mechanisms in the hippocampus during memory formation".

    Science.gov (United States)

    Mathew, Rebecca S; Mullan, Hillary; Blusztajn, Jan Krzysztof; Lehtinen, Maria K

    2016-07-29

    Cho et al. (Reports, 2 October 2015, p. 82) report that gene repression after contextual fear conditioning regulates hippocampal memory formation. We observe low levels of expression for many of the top candidate genes in the hippocampus and robust expression in the choroid plexus, as well as repression at 4 hours after contextual fear conditioning, suggesting the inclusion of choroid plexus messenger RNAs in Cho et al. hippocampal samples.

  4. 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.

  5. Transcriptional profiling reveals regulated genes in the hippocampus during memory formation

    Science.gov (United States)

    Donahue, Christine P.; Jensen, Roderick V.; Ochiishi, Tomoyo; Eisenstein, Ingrid; Zhao, Mingrui; Shors, Tracey; Kosik, Kenneth S.

    2002-01-01

    Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.

  6. Peripheral inflammation increases seizure susceptibility via the induction of neuroinflammation and oxidative stress in the hippocampus

    OpenAIRE

    Ho, Ying-Hao; Lin, Yu-Te; Wu, Chih-Wei J.; Chao, Yung-Mei; Alice Y W Chang; Chan, Julie Y H

    2015-01-01

    Background Neuroinflammation with activation of microglia and production of proinflammatory cytokines in the brain plays an active role in epileptic disorders. Brain oxidative stress has also been implicated in the pathogenesis of epilepsy. Damage in the hippocampus is associated with temporal lobe epilepsy, a common form of epilepsy in human. Peripheral inflammation may exacerbate neuroinflammation and brain oxidative stress. This study examined the impact of peripheral inflammation on seizu...

  7. Pharmacological characterisation of the histamine H3 receptor in the rat hippocampus.

    Science.gov (United States)

    Alves-Rodrigues, A; Timmerman, H; Willems, E; Lemstra, S; Zuiderveld, O P; Leurs, R

    1998-03-30

    The purpose of this report was to pharmacologically characterise the histamine H3 in the rat hippocampus using radioligand binding studies with the H3 receptor antagonist [125I]iodophenpropit and the H3 receptor mediated inhibition of [3H]noradrenaline release. A dissociation constant of 0.33 nM and a maximal number of binding sites of 125 fmol/mg protein were found for [125I]iodophenpropit. Competition studies showed stereoselectivity for the (R) and (S) enantiomers of alpha-methylhistamine and 10 microM of GTPgammaS shifted the curve of (R)-alpha-methylhistamine rightwards. Up to 1 microM, (R)-alpha-methylhistamine displaced only 30% whereas the tested H3-antagonists displaced 50-60% of the total [125I]iodophenpropit bound. This indicates the presence of an additional non-H3 receptor binding site(s) for [125I]iodophenpropit in the rat hippocampus. This secondary site shows low affinity for H3 agonists, but high affinity for the tested H3 antagonists. Electrically evoked [3H]acetylcholine release was shown in slices of rat hippocampus. No H3 receptor modulation of [3H]acetylcholine release from hippocampal slices was detectable. However, H3 receptor activation inhibited 42% of the electrically-evoked [3H]noradrenaline release in rat hippocampal slices. The inhibition of [3H]noradrenaline release was effectively antagonized by the H3 antagonists thioperamide and burimamide. We describe the pharmacological identification of the histamine H3 receptor in the rat hippocampus and its similarities and differences from the cortical H3 receptor. These studies enable us to investigate changes in density and functionality of the hippocampal H3 receptor under (patho)physiological conditions.

  8. Neural correlates of object-in-place learning in hippocampus and prefrontal cortex

    Science.gov (United States)

    Kim, Jangjin; Delcasso, Sébastien; Lee, Inah

    2011-01-01

    Hippocampus and prefrontal cortex (PFC) process spatiotemporally discrete events while maintaining goal-directed task demands. Although some studies have reported that neural activities in the two regions are coordinated, such observations have rarely been reported in an object-place paired-associate (OPPA) task in which animals must learn an object-in-place rule. In this study, we recorded single units and local field potentials simultaneously from the CA1 subfield of the hippocampus and PFC as rats learned that object A, but not object B, was rewarded in place 1, but not in place 2 (vice versa for object B). Both hippocampus and PFC are required for normal performance in this task. PFC neurons fired in association with the regularity of the occurrence of a certain type of event independent of space, whereas neuronal firing in CA1 was spatially localized for representing a discrete place. Importantly, the differential firing patterns were observed in tandem with common learning-related changes in both regions. Specifically, once OPPA learning occurred and rats used an object-in-place strategy, (i) both CA1 and PFC neurons exhibited spatially more similar and temporally more synchronized firing patterns, (ii) spiking activities in both regions were more phase-locked to theta rhythms, (iii) CA1-mPFC coherence in theta oscillation was maximal before entering a critical place for decision making. The results demonstrate differential as well as common neural dynamics between hippocampus and PFC in acquiring the OPPA task and strongly suggest that both regions form a unified functional network for processing an episodic event. PMID:22114269

  9. Cellular and network mechanisms generating spontaneous population events in the immature rat hippocampus

    OpenAIRE

    SipilÀ, Sampsa

    2006-01-01

    Distinct endogenous network events, generated independently of sensory input, are a general feature of various structures of the immature central nervous system. In the immature hippocampus, these type of events are seen as "giant depolarizing potentials" (GDPs) in intracellular recordings in vitro. GABA, the major inhibitory neurotransmitter of the adult brain, has a depolarizing action in immature neurons, and GDPs have been proposed to be driven by GABAergic transmission. Moreover, GDPs ha...

  10. Morphology of CA3 non-pyramidal cells in the developing rat hippocampus.

    OpenAIRE

    Gaïarsa, Jean-Luc; Khalilov, Ilgam; Gozlan, Henri; Ben-Ari, Yehezkel

    2001-01-01

    International audience; Although several investigations have shown that the local GABAergic circuit in the rat hippocampus is functional very early in development, this result has not been yet completed by the investigation of the full dendritic and axonal arborization of the neonatal interneurones. In the present study, intracellular injection of biocytin was used to assess the branching pattern of interneurones in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their...

  11. Status epilepticus results in reversible neuronal injury in infant rat hippocampus: novel use of a marker

    OpenAIRE

    Chang, Daniel; Tallie Z. Baram

    1994-01-01

    Despite ready induction of severe limbic status epilepticus by systemic kainic acid (KA) in infant rats, excitotoxic neuronal injury has not been observed. The mechanisms of this resistance of the immature hippocampus to excitotoxicity are unknown. Acid fuchsin stain has been used as a marker of irreversibly injured neurons in the adult brain. We speculated that the dye might map reversibly injured neurons in the infant. Subsequent to KA-induced status epilepticus in 11-day-old rats, acid fuc...

  12. Similarity in form and function of the hippocampus in rodents, monkeys, and humans

    OpenAIRE

    2013-01-01

    We begin by describing an historical scientific debate in which the fundamental idea that species are related by evolutionary descent was challenged. The challenge was based on supposed neuroanatomical differences between humans and other primates with respect to a structure known then as the hippocampus minor. The debate took place in the early 1860s, just after the publication of Darwin’s famous book. We then recount the difficult road that was traveled to develop an animal model of human m...

  13. Learning and nicotine interact to increase CREB phosphorylation at the jnk1 promoter in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Justin W Kenney

    Full Text Available Nicotine is known to enhance long-term hippocampus dependent learning and memory in both rodents and humans via its activity at nicotinic acetylcholinergic receptors (nAChRs. However, the molecular basis for the nicotinic modulation of learning is incompletely understood. Both the mitogen activated protein kinases (MAPKs and cAMP response element binding protein (CREB are known to be integral to the consolidation of long-term memory and the disruption of MAPKs and CREB are known to abrogate some of the cognitive effects of nicotine. In addition, the acquisition of contextual fear conditioning in the presence of nicotine is associated with a β2-subunit containing nAChR-dependent increase in jnk1 (mapk8 transcription in the hippocampus. In the present study, chromatin immunoprecipitation (ChIP was used to examine whether learning and nicotine interact to alter transcription factor binding or histone acetylation at the jnk1 promoter region. The acquisition of contextual fear conditioning in the presence of nicotine resulted in an increase in phosphorylated CREB (pCREB binding to the jnk1 promoter in the hippocampus in a β2-subunit containing nAChR dependent manner, but had no effect on CREB binding; neither fear conditioning alone nor nicotine administration alone altered transcription factor binding to the jnk1 promoter. In addition, there were no changes in histone H3 or H4 acetylation at the jnk1 promoter following fear conditioning in the presence of nicotine. These results suggest that contextual fear learning and nicotine administration act synergistically to produce a unique pattern of protein activation and gene transcription in the hippocampus that is not individually generated by fear conditioning or nicotine administration alone.

  14. Impairment of synaptic development in the hippocampus of diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Matsunaga, Yuki; Negishi, Takayuki; Hatakeyama, Akinori; Kawagoe, Yuta; Sawano, Erika; Tashiro, Tomoko

    2016-10-01

    Insulin receptor signaling has been shown to regulate essential aspects of CNS function such as synaptic plasticity and neuronal survival. To elucidate its roles during CNS development in vivo, we examined the synaptic and cognitive development of the spontaneously diabetic Goto-Kakizaki (GK) rats in the present study. GK rats are non-obese models of type 2 diabetes established by selective inbreeding of Wistar rats based on impaired glucose tolerance. Though they start exhibiting only moderate hyperglycemia without changes in plasma insulin levels from 3 weeks postnatally, behavioral alterations in the open-field as well as significant impairments in memory retention compared with Wistar rats were observed at 10 weeks and were worsened at 20 weeks. Alterations in insulin receptor signaling and signs of insulin resistance were detected in the GK rat hippocampus at 3 weeks, as early as in other insulin-responsive peripheral tissues. Significant reduction of an excitatory postsynaptic scaffold protein, PSD95, was found at 5w and later in the hippocampus of GK rats due to the absence of a two-fold developmental increase of this protein observed in Wistar control rats between 3 and 20w. In the GK rat hippocampus, NR2A which is a NMDA receptor subunit selectively anchored to PSD95 was also reduced. In contrast, both NR2B and its anchoring protein, SAP102, showed similar developmental profiles in Wistar and GK rats with expression peaks at 2 and 3w. The results suggest that early alterations in insulin receptor signaling in the GK rat hippocampus may affect cognitive performance by suppressing synaptic maturation.

  15. A computational model of the hippocampus that represents environmental structure and goal location, and guides movement.

    Science.gov (United States)

    Matsumoto, Jumpei; Makino, Yoshinari; Miura, Haruki; Yano, Masafumi

    2011-08-01

    Hippocampal place cells (PCs) are believed to represent environmental structure. However, it is unclear how and which brain regions represent goals and guide movements. Recently, another type of cells that fire around a goal was found in rat hippocampus (we designate these cells as goal place cells, GPCs). This suggests that the hippocampus is also involved in goal representation. Assuming that the activities of GPCs depend on the distance to a goal, we propose an adaptive navigation model. By monitoring the population activity of GPCs, the model navigates to shorten the distance to the goal. To achieve the distance-dependent activities of GPCs, plastic connections are assumed between PCs and GPCs, which are modified depending on two reward-triggered activities: activity propagation through PC-PC network representing the topological environmental structure, and the activity of GPCs with different durations. The former activity propagation is regarded as a computational interpretation of "reverse replay" phenomenon found in rat hippocampus. Simulation results confirm that after reaching a goal only once, the model can navigate to the goal along almost the shortest path from arbitrary places in the environment. This indicates that the hippocampus might play a primary role in the representation of not only the environmental structure but also the goal, in addition to guiding the movement. This navigation strategy using the population activity of GPCs is equivalent to the taxis strategy, the simplest and most basic for biological systems. Our model is unique because this simple strategy allows the model to follow the shortest path in the topological map of the environment.

  16. Acute administration of l-tyrosine alters energetic metabolism of hippocampus and striatum of infant rats.

    Science.gov (United States)

    Ramos, Andrea C; Ferreira, Gabriela K; Carvalho-Silva, Milena; Furlanetto, Camila B; Gonçalves, Cinara L; Ferreira, Gustavo C; Schuck, Patrícia F; Streck, Emilio L

    2013-08-01

    Tyrosinemia type II is an inborn error of metabolism caused by mutations in the gene that encodes tyrosine aminotransferase, which leads to increased blood tyrosine levels. Considering that tyrosine levels are highly elevated in fluids of patients with tyrosinemia type II, and that previous studies demonstrated significant alterations in brain energy metabolism of young rats caused by l-tyrosine, the present study aimed to evaluate the effect of acute administration of l-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase, and mitochondrial respiratory chain complexes I, II, II-III, and IV in posterior cortex, hippocampus, and striatum of infant rats. Wistar rats (10 days old) were killed 1h after a single intraperitoneal injection of tyrosine (500 mg/kg) or saline. The activities of energy metabolism enzymes were evaluated in brain of rats. Our results demonstrated that acute administration of l-tyrosine inhibited the activity of citrate synthase activity in striatum and increased the activities of malate dehydrogenase and succinate dehydrogenase in hippocampus. On the other hand, these enzymes were not affected in posterior cortex. The activities of complex I and complex II were inhibited by acute administration of l-tyrosine in striatum. On the other hand, the acute administration of l-tyrosine increased the activity of activity of complex II-III in hippocampus. Complex IV was not affected by acute administration of l-tyrosine in infant rats. Our results indicate an alteration in the energy metabolism in hippocampus and striatum of infant rats after acute administration of l-tyrosine. If the same effects occur in the brain of the patients, it is possible that energy metabolism impairment may be contribute to possible damage in memory and cognitive processes in patients with tyrosinemia type II.

  17. Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    LIU Huan-guang; YANG An-chao; MENG Da-wei; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures.In this study,we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.Methods Three groups of rats were used:(1) a stimulation group (n=12),(2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA),and (3) a control group (n=12) with sham surgery.Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT.High-frequency stimulation was performed in each group except the sham stimulation group.Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in thestimulation group.The concentrations of glucose,lactate,and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.Results The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020,P=0.001; respectively).However,no significant difference in the concentration of glucose and pyruvate was found between these groups (P>0.05).Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05),but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).Conclusions This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation.These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

  18. Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory.

    Science.gov (United States)

    Duffy, S N; Craddock, K J; Abel, T; Nguyen, P V

    2001-01-01

    cAMP-dependent protein kinase (PKA) is critical for the expression of some forms of long-term potentiation (LTP) in area CA1 of the mouse hippocampus and for hippocampus-dependent memory. Exposure to spatially enriched environments can modify LTP and improve behavioral memory in rodents, but the molecular bases for the enhanced memory performance seen in enriched animals are undefined. We tested the hypothesis that exposure to a spatially enriched environment may alter the PKA dependence of hippocampal LTP. Hippocampal slices from enriched mice showed enhanced LTP following a single burst of 100-Hz stimulation in the Schaffer collateral pathway of area CA1. In slices from nonenriched mice, this single-burst form of LTP was less robust and was unaffected by Rp-cAMPS, an inhibitor of PKA. In contrast, the enhanced LTP in enriched mice was attenuated by Rp-cAMPS. Enriched slices expressed greater forskolin-induced, cAMP-dependent synaptic facilitation than did slices from nonenriched mice. Enriched mice showed improved memory for contextual fear conditioning, whereas memory for cued fear conditioning was unaffected following enrichment. Our data indicate that exposure of mice to spatial enrichment alters the PKA dependence of LTP and enhances one type of hippocampus-dependent memory. Environmental enrichment can transform the pharmacological profile of hippocampal LTP, possibly by altering the threshold for activity-dependent recruitment of the cAMP-PKA signaling pathway following electrical and chemical stimulation. We suggest that experience-dependent plasticity of the PKA dependence of hippocampal LTP may be important for regulating the efficacy of hippocampus-based memory.

  19. GABA and Glutamate are not colocalized in mossy fiber terminals of developing rodent hippocampus

    OpenAIRE

    Xiong, Guoxiang; Zhang, Lei; Mojsilovic-Petrovic, Jelena; Arroyo, Edguardo; Elkind, Jaclynn; Kundu, Suhali; Johnson, Brian; Smith, Colin J.; Cohen, Noam A.; Grady, Sean M.; Cohen, Akiva S.

    2012-01-01

    It has been hypothesized that, in the developing rodent hippocampus, mossy fiber terminals release GABA together with glutamate. Here, we used transgenic glutamic acid decarboxylase-67 (GAD67)-GFP expressing mice and multi-label immunohistochemistry to address whether glutamatergic and GABAergic markers are colocalized. We demonstrate that in the dentate gyrus, interneurons positive for GABA/GAD are sparsely distributed along the edge of the hilus, in a different pattern than the densely pack...

  20. Interneurons Differentially Contribute to Spontaneous Network Activity in the Developing Hippocampus Dependent on Their Embryonic Lineage

    OpenAIRE

    Wester, Jason C.; McBain, Chris J.

    2016-01-01

    Spontaneously generated network activity is a hallmark of developing neural circuits, and plays an important role in the formation of synaptic connections. In the rodent hippocampus, this activity is observed in vitro as giant depolarizing potentials (GDPs) during the first postnatal week. Interneurons importantly contribute to GDPs, due to the depolarizing actions of GABA early in development. While they are highly diverse, cortical interneurons can be segregated into two distinct groups bas...

  1. Peripheral challenge with a viral mimic upregulates expression of the complement genes in the hippocampus

    OpenAIRE

    Michalovicz, Lindsay T.; Lally, Brent; Konat, Gregory W.

    2015-01-01

    Peripheral challenge with a viral mimetic, polyinosinic-polycytidylic acid (PIC) induces hippocampal hyperexcitability in mice. Here, we characterized this hippocampal response through a whole genome transcriptome analysis. Intraperitoneal injection of PIC resulted in temporal dysregulation of 625 genes in the hippocampus, indicating an extensive genetic reprogramming. The bioinformatics analysis of these genes revealed the complement pathway to be the most significantly activated. The gene e...

  2. Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Filipa I Baptista

    Full Text Available Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM or mannitol (osmotic control; 25 mM plus 25 mM glucose for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal

  3. NADPH diaphorase-positive neurons in the lizard hippocampus: a distinct subpopulation of GABAergic interneurons.

    Science.gov (United States)

    Dávila, J C; Megías, M; Andreu, M J; Real, M A; Guirado, S

    1995-01-01

    We analyzed the distribution and light-microscopic features of the NADPH diaphorase-containing structures in the lizard hippocampus, likely to correspond to nitric oxide synthase-containing cells and fibers, and thus likely to release nitric oxide. We also studied co-localization of NADPH diaphorase with the neurotransmitter GABA, the calcium-binding protein parvalbumin, and the neuropeptide somatostatin, in order to examine whether putative nitric oxide-synthesizing neurons represent a different subpopulation of GABA cells, on which the authors recently reported in lizards. We also studied co-localization of NADPH diaphorase with parvalbumin or somatostatin in mice to ascertain whether the characteristics of this population in reptiles parallel the situation in mammals. Most of the positive NADPH diaphorase neurons were stained in a Golgi-like manner and were in the plexiform layers of the lizard hippocampus with morphologies ranging from bipolar to multipolar. Co-localization with GABA was 100%, and NADPH diaphorase-positive neurons in the lizard hippocampus did not contain parvalbumin or somatostatin. The results indicate that putative nitric oxide-synthesizing neurons represent a distinct subpopulation of GABA interneurons in the lizard hippocampus. Two different types of fibers were described in the plexiform layers: one type bearing thick varicosities, and the other thinner ones. We discuss the possibility that at least part of the positive fibers arise from a hypothalamic aminergic nucleus contacting the third ventricle, the periventricular hypothalamic organ. Most radial glia were stained almost completely and formed typical end-feet both at the pia and around capillaries. The results of this study confirm that the capacity for synthesizing nitric oxide is linked to a determined set of neuronal markers depending on the specific brain region, and they provide new resemblances between hippocampal regions in different classes of vertebrates.

  4. Non-granule PSA-NCAM immunoreactive neurons in the rat hippocampus.

    Science.gov (United States)

    Nacher, Juan; Blasco-Ibáñez, José M; McEwen, Bruce S

    2002-03-15

    The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) continues to be expressed in the adult hippocampus, mainly in a subset of neurons located in the innermost portion of the granule cell layer. PSA-NCAM immunoreactive neurons have also been described outside this layer in humans, where they are severely reduced in schizophrenic brains. Given this important clinical implication, we were interested in finding whether similar neurons existed in the adult rat hippocampus and to characterize their distribution, morphology and phenotype. PSA-NCAM immunocytochemistry reveals labeled neurons in the subiculum, fimbria, alveus, hilus, and stratum oriens, lucidum and radiatum of CA3 and CA1. They are mainly distributed in the ventral hippocampus, and have polygonal or fusiform somata with multipolar or bipolar morphology. These neurons show long straight dendrites, which reach several strata and even enter the fimbria and the alveus. These dendrites are often varicose, appear devoid of excrescences and apparently do not show spines. Most of these neurons display GABA immunoreactivity and further analysis has shown that a subpopulation expresses calretinin, but not somatostatin, neuropeptide Y, parvalbumin, calbindin or NADPH diaphorase. Our study demonstrates that there is an important subpopulation of PSA-NCAM immunoreactive neurons, many of which can be considered interneurons, outside the rat granule cell layer, probably homologous to those described in the human hippocampus. The presence of the polysialylated form of NCAM in these neurons could indicate that they are undergoing continuous remodeling during adulthood and may have an important role in hippocampal structural plasticity.

  5. Synaptic Targets of Medial Septal Projections in the Hippocampus and Extrahippocampal Cortices of the Mouse.

    Science.gov (United States)

    Unal, Gunes; Joshi, Abhilasha; Viney, Tim J; Kis, Viktor; Somogyi, Peter

    2015-12-02

    Temporal coordination of neuronal assemblies among cortical areas is essential for behavioral performance. GABAergic projections from the medial septum and diagonal band complex exclusively innervate GABAergic interneurons in the rat hippocampus, contributing to the coordination of neuronal activity, including the generation of theta oscillations. Much less is known about the synaptic target neurons outside the hippocampus. To reveal the contribution of synaptic circuits involving the medial septum of mice, we have identified postsynaptic cortical neurons in wild-type and parvalbumin-Cre knock-in mice. Anterograde axonal tracing from the septum revealed extensive innervation of the hippocampus as well as the subiculum, presubiculum, parasubiculum, the medial and lateral entorhinal cortices, and the retrosplenial cortex. In all examined cortical regions, many septal GABAergic boutons were in close apposition to somata or dendrites immunopositive for interneuron cell-type molecular markers, such as parvalbumin, calbindin, calretinin, N-terminal EF-hand calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules. Electron microscopic observations revealed septal boutons forming axosomatic or axodendritic type II synapses. In the CA1 region of hippocampus, septal GABAergic projections exclusively targeted interneurons. In the retrosplenial cortex, 93% of identified postsynaptic targets belonged to interneurons and the rest to pyramidal cells. These results suggest that the GABAergic innervation from the medial septum and diagonal band complex contributes to temporal coordination of neuronal activity via several types of cortical GABAergic interneurons in both hippocampal and extrahippocampal cortices. Oscillatory septal neuronal firing at delta, theta, and gamma frequencies may phase interneuron activity.

  6. Intracerebroventricular injection of lipopolysaccharide increases gene expression of connexin32 gap junction in rat hippocampus.

    Science.gov (United States)

    Abbasian, Mohammad; Sayyah, Mohammad; Babapour, Vahab; Mahdian, Reza

    2013-01-01

    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. 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. 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. 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.

  7. Proteome Analysis of Rat Hippocampus Following Morphine-induced Amnesia and State-dependent Learning.

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    Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Rezayof, Ameneh; Darbandi, Niloufar

    2015-01-01

    Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.

  8. High temperatures alter physiological properties of pyramidal cells and inhibitory interneurons in hippocampus

    OpenAIRE

    Kim, Jennifer A; Barry W Connors

    2012-01-01

    Temperature has multiple effects on neurons, yet little is known about the effects of high temperature on the physiology of mammalian central neurons. Hyperthermia can influence behavior and cause febrile seizures. We studied the effects of acute hyperthermia on the immature hippocampus in vitro by recording from pyramidal neurons and inhibitory oriens-lacunosum moleculare (O-LM) interneurons (identified by green fluorescent protein (GFP) expression in the GIN mouse line). Warming to 41°C cau...

  9. Distribution of interneurons in the CA2 region of the rat hippocampus.

    OpenAIRE

    Botcher, N. A.; Falck, J. E.; Thomson, A. M.; Mercer, A.

    2014-01-01

    The CA2 region of the mammalian hippocampus is a unique region with its own distinctive properties, inputs and pathologies. Disruption of inhibitory circuits in this region appears to be linked with the pathology of specific psychiatric disorders, promoting interest in its local circuitry, its role in hippocampal function and its dysfunction in disease. In previous studies, CA2 interneurons, including a novel subclass of CA2 dendrite-preferring interneurons that has not been identified in oth...

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

    OpenAIRE

    Nikolaos P Daskalakis; Edo Ronald eDe Kloet; Rachel eYehuda; Dolores eMalaspina; 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 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 guidan...

  11. Response of the contralateral hippocampus to lateral fluid percussion brain injury.

    Science.gov (United States)

    Tran, Lorriann D; Lifshitz, Jonathan; Witgen, Brent M; Schwarzbach, Elizabeth; Cohen, Akiva S; Grady, M Sean

    2006-09-01

    Traumatic brain injury is a leading cause of death and disability in the United States. Pathological examinations of humans and animal models after brain injury demonstrate hippocampal neuronal damage, which may contribute to cognitive impairments. Data from our laboratories have shown that, at 1 week after brain injury, mice possess significantly fewer neurons in all ipsilateral hippocampal subregions and a cognitive impairment. Since cognitive function is distributed across both cerebral hemispheres, the present paper explores the morphological and physiological response of the contralateral hippocampus to lateral brain injury. We analyzed the contralateral hippocampus using design-based stereology, Fluoro-Jade (FJ) histochemistry, and extracellular field recordings in mice at 7 and 30 days after lateral fluid percussion injury (FPI). At 7 days, all contralateral hippocampal subregions possess significantly fewer healthy neurons compared to sham-injured animals and demonstrate FJ-positive neuronal damage, but not at 30 days. Both the ipsilateral and contralateral dentate gyri demonstrate significantly increased excitability at 7 days post-injury, but only ipsilateral dentate gyrus hyperexcitability persists at 30 days compared to sham. In the contralateral hippocampus, the transient decrease in the number of healthy neurons, concomitant with FJ damage, and electrophysiological alterations establish a stunned period of cellular and circuit dysfunction. The return of healthy neuron number, absence of FJ damage, and sham level of excitability in the contralateral hippocampus suggest recovery of structure and function by 30 days after injury. The cognitive recovery observed after human traumatic brain injury may stem from a differential injury exposure and time course of recovery between homologous regions of the two hemispheres.

  12. Morphological Effects of Hydroalcoholic Zingiber Officinalis Extract in the Murine Hippocampus of Male Rat Offspring

    Directory of Open Access Journals (Sweden)

    Ghodrati

    2016-02-01

    Full Text Available Background The hippocampus is responsible for memory. A diet full of antioxidants improves brain damage and cognitive function. Regard the antioxidant effects of zingiber officinalis (ginger and its flavonoids components. Objectives The aim of this study was to evaluate the effect of the extract of ginger on memory by using hippocampus tissue of the male offspring of rats. Materials and Methods In this study, 60 rats, 15 males and 45 females, were used. We separated pregnant female rats from males on the first day of pregnancy (determined by vaginal plug, and during days 16 - 18 of pregnancy, via intraperitoneal injection, three groups received hydroalcoholic extract of ginger, with low (200 mg/kg bw, medium (400 mg/kg bw, and high (800 mg/kg bw concentration doses. The control group did not receive anything, and the sham group received normal saline during these days. Then at day 50, the males offspring in each group were sacrificed, their brains were removed, and the hippocampus sections were prepared for microscopic studies. Data was analyzed by SPSS 20 and by using one-way ANOVA and then a Tukey post-test (P < 0.05 considered as the significance level. Results This research showed that the number and thickness of pyramidal and granular layers of the CA1 and dentate gyrus areas of the hippocampus had increased in male offspring according to the increase in the ginger extract dose. Conclusions It seems as though ginger extract, which contains compounds such as gingerols, shogaols, and zingerone, can affect memory ability in rats through these compounds’ antioxidant properties by affecting embryonic acetylcholine content and place cells.

  13. Impaired familiarity with preserved recollection after anterior temporal-lobe resection that spares the hippocampus.

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    Bowles, Ben; Crupi, Carina; Mirsattari, Seyed M; Pigott, Susan E; Parrent, Andrew G; Pruessner, Jens C; Yonelinas, Andrew P; Köhler, Stefan

    2007-10-09

    It is well established that the medial-temporal lobe (MTL) is critical for recognition memory. The MTL is known to be composed of distinct structures that are organized in a hierarchical manner. At present, it remains controversial whether lower structures in this hierarchy, such as perirhinal cortex, support memory functions that are distinct from those of higher structures, in particular the hippocampus. Perirhinal cortex has been proposed to play a specific role in the assessment of familiarity during recognition, which can be distinguished from the selective contributions of the hippocampus to the recollection of episodic detail. Some researchers have argued, however, that the distinction between familiarity and recollection cannot capture functional specialization within the MTL and have proposed single-process accounts. Evidence supporting the dual-process view comes from demonstrations that selective hippocampal damage can produce isolated recollection impairments. It is unclear, however, whether temporal-lobe lesions that spare the hippocampus can produce selective familiarity impairments. Without this demonstration, single-process accounts cannot be ruled out. We examined recognition memory in NB, an individual who underwent surgical resection of left anterior temporal-lobe structures for treatment of intractable epilepsy. Her resection included a large portion of perirhinal cortex but spared the hippocampus. The results of four experiments based on three different experimental procedures (remember-know paradigm, receiver operating characteristics, and response-deadline procedure) indicate that NB exhibits impaired familiarity with preserved recollection. The present findings thus provide a crucial missing piece of support for functional specialization in the MTL.

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

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    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.

  15. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  16. G-Protein-Coupled Estrogen Receptor 1 Is Anatomically Positioned to Modulate Synaptic Plasticity in the Mouse Hippocampus

    OpenAIRE

    Elizabeth M. Waters; Thompson, Louisa I.; Patel, Parth; Gonzales, Andreina D.; Ye, Hector (Zhiyu); Filardo, Edward J.; Clegg, Deborah J.; Gorecka, Jolanta; Akama, Keith T.; McEwen, Bruce S.; Milner, Teresa A.

    2015-01-01

    Both estrous cycle and sex affect the numbers and types of neuronal and glial profiles containing the classical estrogen receptors α and β, and synaptic levels in the rodent dorsal hippocampus. Here, we examined whether the membrane estrogen receptor, G-protein-coupled estrogen receptor 1 (GPER1), is anatomically positioned in the dorsal hippocampus of mice to regulate synaptic plasticity. By light microscopy, GPER1-immunoreactivity (IR) was most noticeable in the pyramidal cell layer and int...

  17. Immunoreactivity of S100β protein in the hippocampus of chinchilla

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    Krawczyk Aleksandra

    2014-03-01

    Full Text Available The aim of the study was to investigate S100β protein in astrocytes of CA1 and CA3 areas of the hippocampus proper and the dentate gyrus with the hilus yet undefined in mature males of chinchilla. The presence of S100β was determined using indirect immunohistochemical peroxidase-antiperoxidase method with specific monoclonal antibody against this protein. Most of the S100β-positive cells were detected in the subgranular zone of the dentate gyrus and in the middle part of the hilus. In CA3 area, it was found that the most numerous cells with S100β are in stratum radiatum. In CA1 area, there were single astrocytes expressing this protein. This data demonstrates species differences and a large quantity of S100β immunoreactive cells in the subgranular zone of the dentate gyrus of chinchilla, which may be associated with structural reorganisation of the hippocampus and with neurogenesis, learning, and memorising process dependent on the hippocampus.

  18. The effects of concomitant Ginkgo intake on noise induced Hippocampus injury. Possible auditory clinical correlate

    Directory of Open Access Journals (Sweden)

    Alaa Abousetta

    2014-11-01

    Full Text Available This study was conducted to determine the injurious effects of noise on the hippocampus, and to show whether Ginkgo biloba (Gb has any modulatory effect on hippocampal injury. Fifteen adult male albino rats were divided into three groups; control group, noise group and protected group. The noise group was exposed to 100 dB Sound pressure level (SPL white noise, six hours/day for four consecutive weeks. The protected group was exposed to the same noise level with the administration of Gb extract to the animals (50 mg/kg daily for 4 weeks. In the noise exposed group, both pyramidal cell layer and dentate gyrus (DG granular cell layer showed a decrease in thickness with loss and degeneration of many cells. The protected group showed preservation of many parameters as compared to the noise group i.e. increase in thickness of Cornu Ammonis area3 (CA3 & DG; increase in surface area of cells and increased vascularity. In conclusion, noise had detrimental effects on cells of Cornu Ammonis area1 (CA1, CA3 & DG of the hippocampus. In view of this finding, the clinical auditory hazardous effects in people exposed to harmful noise such as tinnitus, as well as memory disturbances and learning disabilities might have a new dimension. The administration of Gb protected the hippocampus against the injurious effect of noise. The probable mechanism and usefulness of Gb in reducing the previously mentioned effects are discussed.

  19. 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

  20. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    Science.gov (United States)

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  1. The hippocampus: A central node in a large-scale brain network for memory.

    Science.gov (United States)

    Huijgen, J; Samson, S

    2015-03-01

    The medial temporal lobe is a key region in the formation and consolidation of conscious or declarative memories. In this review, we will first consider the role of the hippocampus and its surrounding medial temporal lobe structures in recognition memory from a historical perspective. According to the dual process model of recognition memory, recognition judgments can be based on the recollection of details about previous presented stimuli or on the feeling of familiarity. Studies in humans, primates and rodents suggest that the hippocampus, the parahippocampal cortex and the perirhinal cortex play different roles in recollection and familiarity. Then, we will describe the role of the hippocampus and neocortex in memory consolidation: a process in which novel memories become integrated into long-term memory. After presenting possible mechanisms underlying sleep-dependent declarative memory consolidation, we will discuss the phenomenon of accelerated long-term forgetting. This type of memory deficit is often observed in epileptic patients with a hippocampal lesion, and provides a novel opportunity to investigate post-encoding and memory consolidation processes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. 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.

  3. Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

    Science.gov (United States)

    Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

    2016-10-01

    Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Astaxanthin rescues neuron loss and attenuates oxidative stress induced by amygdala kindling in adult rat hippocampus.

    Science.gov (United States)

    Lu, Yan; Xie, Tao; He, Xue-Xin; Mao, Zhuo-Feng; Jia, Li-Jing; Wang, Wei-Ping; Zhen, Jun-Li; Liu, Liang-Min

    2015-06-15

    Oxidative stress plays an important role in the neuronal damage induced by epilepsy. The present study assessed the possible neuroprotective effects of astaxanthin (ATX) on neuronal damage, in hippocampal CA3 neurons following amygdala kindling. Male Sprague-Dawley rats were chronically kindled in the amygdala and ATX or equal volume of vehicle was given by intraperitoneally. Twenty-four hours after the last stimulation, the rats were sacrificed by decapitation. Histopathological changes and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and reduced glutathione (GSH) were measured, cytosolic cytochrome c (CytC) and caspase-3 activities in the hippocampus were also recorded. We found extensive neuronal damage in the CA3 region in the kindling group, which was preceded by increases of ROS level and MDA concentration and was followed by caspase-3 activation and an increase in cytosolic CytC. Treatment with ATX markedly attenuated the neuronal damage. In addition, ATX significantly decreased ROS and MDA concentrations and increased GSH levels. Moreover, ATX suppressed the translation of CytC release and caspase-3 activation in hippocampus. Together, these results suggest that ATX protects against neuronal loss due to epilepsy in the rat hippocampus by attenuating oxidative damage, lipid peroxidation and inhibiting the mitochondrion-related apoptotic pathway.

  5. Activation of Nrf2-ARE signal pathway in hippocampus of amygdala kindling rats.

    Science.gov (United States)

    Wang, Wei; Wang, Wei-Ping; Zhang, Guo-Liang; Wu, Yan-Fen; Xie, Tao; Kan, Min-Chen; Fang, Hai-Bo; Wang, Hong-Chao

    2013-05-24

    Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies have received considerable attention in epilepsy treatment. It is well known that the transcription factor NF-E2-related factor (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative stress and accumulation of toxic metabolites. However, whether Nrf2-ARE pathway is activated after seizure has not been studied. In the present study, Wistar rats were rapidly kindled in the amygdala. Twenty-four hours after the last seizure, the hippocampus of control, sham and kindled rats were examined for oxidative stress parameters (malondialdehyde and glutathione) by spectrophotometry, the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) were determined using immunohistochemistry, Western blot and real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that the kindled seizures induced oxidative stress, the expression of Nrf2, HO-1 and NQO1 at protein or gene levels significantly increased in hippocampus after seizure. According to these results, it could be postulated that Nrf2-ARE signal pathway was activated in the hippocampus after seizure.

  6. Spatial Olfactory Learning Contributes to Place Field Formation in the Hippocampus

    Science.gov (United States)

    Zhang, Sijie; Manahan-Vaughan, Denise

    2015-01-01

    Spatial encoding in the hippocampus is multifactorial, and it is well established that metric information about space is conferred by place cells that fire when an animal finds itself in a specific environmental location. Visuospatial contexts comprise a key element in the formation of place fields. Nevertheless, hippocampus does not only use visual cues to generate spatial representations. In the absence of visual input, both humans and other vertebrates studied in this context, are capable of generating very effective spatial representations. However, little is known about the relationship between nonvisual sensory modalities and the establishment of place fields. Substantial evidence exists that olfactory information can be used to learn spatial contexts. Here, we report that learning about a distinct odor constellation in an environment, where visual and auditory cues are suppressed, results in stable place fields that rotate when the odor constellations are rotated and remap when the odor constellations are shuffled. These data support that the hippocampus can use nonvisuospatial resources, and specifically can use spatial olfactory information, to generate spatial representations. Despite the less precise nature of olfactory stimuli compared with visual stimuli, these can substitute for visual inputs to enable the acquisition of metric information about space. PMID:24008582

  7. Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus.

    Science.gov (United States)

    Hundahl, Christian Ansgar; Fahrenkrug, Jan; Hannibal, Jens

    2014-09-01

    Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority of tissues and has been proposed to function in nitric oxide (NO) metabolism in the vasculature and to have cytoprotective properties. However, the overall functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin- and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool in determining the function of Cygb in the brain.

  8. Differential roles of the dorsal and ventral hippocampus in predator odor contextual fear conditioning.

    Science.gov (United States)

    Wang, Melissa E; Fraize, Nicolas P; Yin, Linda; Yuan, Robin K; Petsagourakis, Despina; Wann, Ellen G; Muzzio, Isabel A

    2013-06-01

    The study of fear memory is important for understanding various anxiety disorders in which patients experience persistent recollections of traumatic events. These memories often involve associations of contextual cues with aversive events; consequently, Pavlovian classical conditioning is commonly used to study contextual fear learning. The use of predator odor as a fearful stimulus in contextual fear conditioning has become increasingly important as an animal model of anxiety disorders. Innate fear responses to predator odors are well characterized and reliable; however, attempts to use these odors as unconditioned stimuli in fear conditioning paradigms have proven inconsistent. Here we characterize a contextual fear conditioning paradigm using coyote urine as the unconditioned stimulus. We found that contextual conditioning induced by exposure to coyote urine produces long-term freezing, a stereotypic response to fear observed in mice. This paradigm is context-specific and parallels shock-induced contextual conditioning in that it is responsive to extinction training and manipulations of predator odor intensity. Region-specific lesions of the dorsal and ventral hippocampus indicate that both areas are independently required for the long-term expression of learned fear. These results in conjunction with c-fos immunostaining data suggest that while both the dorsal and ventral hippocampus are required for forming a contextual representation, the ventral region also modulates defensive behaviors associated with predators. This study provides information about the individual contributions of the dorsal and ventral hippocampus to ethologically relevant fear learning.

  9. A Stereological Study of Synapse Number in the Epileptic Human Hippocampus

    Science.gov (United States)

    Alonso-Nanclares, Lidia; Kastanauskaite, Asta; Rodriguez, Jose-Rodrigo; Gonzalez-Soriano, Juncal; DeFelipe, Javier

    2011-01-01

    Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity. PMID:21390290

  10. Dual coding with STDP in a spiking recurrent neural network model of the hippocampus.

    Directory of Open Access Journals (Sweden)

    Daniel Bush

    Full Text Available The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain.

  11. Multimodal MRI of the hippocampus in Parkinson's disease with visual hallucinations.

    Science.gov (United States)

    Yao, Nailin; Cheung, Charlton; Pang, Shirley; Shek-kwan Chang, Richard; Lau, Kui Kai; Suckling, John; Yu, Kevin; Ka-Fung Mak, Henry; Chua, Siew Eng; Ho, Shu-Leong; McAlonan, Grainne M

    2016-01-01

    Visual hallucinations carry poor prognosis in Parkinson's disease. Here we tested the hypothesis that the hippocampus and visuospatial memory impairment play a central role in the pathology of PD with visual hallucinations. Multimodal magnetic resonance imaging of the brain was carried out in 12 people with PD and visual hallucinations; 15 PD individuals without hallucinations; and 14 healthy controls. Age, gender, cognitive ability, and education level were matched across the three groups. PD patients were taking dopaminergic medication. Hippocampal volume, shape, mean diffusivity (MD), and functional connectivity within the whole brain were examined. Visuospatial memory was compared between groups, and correlations with hippocampal MD, functional connectivity, and the severity of hallucinations were explored. There were no macrostructural differences across groups, but individuals with hallucinations had higher diffusivity in posterior hippocampus than the other two groups. Visuospatial memory was poorer in both PD groups compared to controls, and was correlated with hallucinations. Finally, hippocampal functional connectivity in the visual cortices was lower in those with hallucinations than other groups, and this correlated with visuospatial memory impairment. In contrast, functional connectivity between the hippocampus and default mode network regions and frontal regions was greater in the PD hallucinators compared to other groups. We suggest that hippocampal pathology, which disrupts visuospatial memory, makes a key contribution to visual hallucinations in PD. These findings may pave the way for future studies of imaging biomarkers to measure treatment response in those with PD who are most at risk of poor outcomes.

  12. High-resolution investigation of memory-specific reinstatement in the hippocampus and perirhinal cortex

    Science.gov (United States)

    Tompary, Alexa; Duncan, Katherine; Davachi, Lila

    2016-01-01

    Episodic memory involves remembering the details that characterize a prior experience. Successful memory recovery has been associated with the reinstatement of brain activity patterns in a number of sensory regions across the cortex. However, how the hippocampus and surrounding medial temporal lobe (MTL) cortex contribute to this process is less clear. Models of episodic memory posit that hippocampal pattern reinstatement, also referred to as pattern completion, may mediate cortical reinstatement during retrieval. Empirical evidence of this process, however, remains elusive. Here, we use high-resolution fMRI and encoding-retrieval multi-voxel pattern similarity analyses to demonstrate for the first time that the hippocampus, particularly right hippocampal subfield CA1, shows evidence of reinstating individual episodic memories. Furthermore, reinstatement in perirhinal cortex (PrC) is also evident. Critically, we identify distinct factors that may mediate the cortical reinstatement in PrC. First, we find that encoding activation in PrC is related to later reinstatement in this region, consistent with the theory that encoding strength in the regions that process the memoranda is important for later reinstatement. Conversely, retrieval activation in right CA1 was correlated with reinstatement in PrC, consistent with models of pattern completion. This dissociation is discussed in the context of the flow of information into and out of the hippocampus during encoding and retrieval, respectively. PMID:26972485

  13. Region-specific differences in amyloid precursor protein expression in the mouse hippocampus

    Directory of Open Access Journals (Sweden)

    Domenico Del Turco

    2016-11-01

    Full Text Available The physiological role of amyloid precursor protein (APP has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and - at the behavioral level - hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus and area CA1 of the mouse hippocampus. We speculated that regional differences in APP expression could underlie these discrepancies and studied the expression of APP in both regions using immunostaining, in situ hybridization, and laser microdissection in combination with quantitative reverse transcription PCR and western blotting. In sum, our results show that APP is approximately 1.7-fold higher expressed in pyramidal cells of Ammon´s horn than in granule cells of the dentate gyrus. This regional difference in APP expression may explain why loss-of-function approaches using APP-deficient mice revealed a role for APP in Hebbian plasticity in area CA1, whereas this could not be shown in the dentate gyrus of the same APP mutants.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Iraj Salehi

    2010-06-01

    Full Text Available Objective(sThe aim of this study was to evaluate the effects of regular exercise in preventing diabetes complication in the hippocampus of streptozotocin (STZ-induced diabetic rat.Materials and MethodsA total of 48 male wistar rats were divided into four groups (control, control exercise, diabetic and diabetic exercise. Diabetes was induced by injection of single dose of STZ. Exercise was performed for one hr every day, over a period of 8 weeks. The antioxidant enzymes (SOD, GPX, CAT and GR and oxidant indexes with brain-derived neurotrophic factor (BDNF protein and its mRNA and apoptosis were measured in hippocampus of rats. ResultsA significant decrease in antioxidant enzymes activities and increased malondialdehyde (MDA level were observed in diabetic rats (P= 0.004. In response to exercise, antioxidant enzymes activities increased (P= 0.004. In contrast, MDA level decreased in diabetic rats (P= 0.004. Induction of diabetes caused an increase of BDNF protein and its mRNA expression. In response to exercise, BDNF protein and its mRNA expression reduced in hippocampus of diabetic rats. ConclusionDiabetes induced oxidative stress and increased BDNF gene expression. Exercise ameliorated oxidative stress and decreased BDNF gene expression.

  16. Posthoc phosphorylation of proteins derived from ischemic rat hippocampus, striatum and neocortex.

    Science.gov (United States)

    Kirschenbaum, B; Pulsinelli, W A

    1990-03-12

    Disruption of the brain's protein phosphorylation system by ischemia may cause irreversible metabolic and structural alterations leading eventually to cell death. To examine the effect of ischemia on the phosphorylation state of brain proteins, tissue homogenates derived from the hippocampus, striatum and neocortex of normal rats and rats subjected to severe forebrain ischemia were phosphorylated with [gamma-32P]ATP. The phosphorylated proteins were separated by two-dimensional polyacrylamide gel electrophoresis and changes were assessed by autoradiography. Cerebral ischemia caused marked alterations of the phosphorylation state of many brain proteins; phosphorylation of some proteins was increased while phosphorylation of others was decreased. Despite differences in the sensitivity of the hippocampus, striatum and neocortex to ischemic injury the direction and approximate magnitude of protein phosphorylation changes caused by ischemia were similar in all three regions. Since the pattern of protein phosphorylation in the ischemia-vulnerable hippocampus was identical to that in the ischemia-resistant paramedian neocortex we conclude that abnormalities of protein phosphorylation may be necessary for ischemic injury to neurons but none are sufficient to explain the selective vulnerability of certain brain regions to ischemic damage.

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

    Science.gov (United States)

    Iidaka, Tetsuya

    2016-10-18

    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.

  18. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

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    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  19. 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.

  20. Regulation of synaptic strength by sphingosine 1-phosphate in the hippocampus.

    Science.gov (United States)

    Kanno, T; Nishizaki, T; Proia, R L; Kajimoto, T; Jahangeer, S; Okada, T; Nakamura, S

    2010-12-29

    Although the hippocampus is a brain region involved in short-term memory, the molecular mechanisms underlying memory formation are not completely understood. Here we show that sphingosine 1-phosphate (S1P) plays a pivotal role in the formation of memory. Addition of S1P to rat hippocampal slices increased the rate of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) recorded from the CA3 region of the hippocampus. In addition long-term potentiation (LTP) observed in the CA3 region was potently inhibited by a sphingosine kinase (SphK) inhibitor and this inhibition was fully reversed by S1P. LTP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1-knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test. These results strongly suggest that SphK/S1P receptor signaling plays an important role in excitatory synaptic transmission in the CA3 region of hippocampus and has profound effects on hippocampal function such as spatial learning.

  1. Shifting gears in hippocampus: temporal dissociation between familiarity and novelty signatures in a single event.

    Science.gov (United States)

    Ben-Yakov, Aya; Rubinson, Mica; Dudai, Yadin

    2014-09-24

    The hippocampus is known to be involved in encoding and retrieval of episodes. However, real-life experiences are expected to involve both encoding and retrieval, and it is unclear how the human hippocampus subserves both functions in the course of a single event. We presented participants with brief movie clips multiple times and examined the effect of familiarity on the hippocampal response at event onset versus event offset. Increased familiarity resulted in a decreased offset response, indicating that the offset response is a novelty-related signature. The magnitude of this offset response was correlated, across hippocampal voxels, with an independent measure of successful encoding, based on nonrepeated clips. This suggests that the attenuated offset response to familiar clips reflects reduced encoding. In addition, the posterior hippocampus exhibited an increased onset response to familiar events, switching from an online familiarity signal to an offline novelty signal during a single event. Moreover, participants with stronger memory exhibited increased reactivation of online activity during familiar events, in line with a retrieval signature. Our results reveal a spatiotemporal dissociation between novelty/encoding and familiarity/retrieval signatures, assumed to reflect different computational modes, in response to the same stimulus.

  2. Response of extracellular zinc in the ventral hippocampus against novelty stress.

    Science.gov (United States)

    Takeda, Atsushi; Sakurada, Naomi; Kanno, Shingo; Minami, Akira; Oku, Naoto

    2006-10-01

    An extensive neuronal activity takes place in the hippocampus during exploratory behavior. However, the role of hippocampal zinc in exploratory behavior is poorly understood. To analyze the response of extracellular zinc in the hippocampus against novelty stress, rats were placed for 50 min in a novel environment once a day for 8 days. Extracellular glutamate in the hippocampus was increased during exploratory behavior on day 1, whereas extracellular zinc was decreased. The same phenomenon was observed during exploratory behavior on day 2 and extracellular zinc had returned to the basal level during exploratory behavior on day 8. To examine the significance of the decrease in extracellular zinc in exploratory activity, exploratory behavior was observed during perfusion with 1 mm CaEDTA, a membrane-impermeable zinc chelator. Locomotor activity in the novel environment was decreased by perfusion with CaEDTA. The decrease in extracellular zinc and the increase in extracellular glutamate in exploratory period were abolished by perfusion with CaEDTA. These results suggest that zinc uptake by hippocampal cells is linked to exploratory activity and is required for the activation of the glutamatergic neurotransmitter system. The zinc uptake may be involved in the response to painless psychological stress or in the cognitive processes.

  3. Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine.

    Science.gov (United States)

    Freitas, R M

    2009-10-25

    The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine in rats, we investigated the lipid peroxidation, nitrite content, superoxide dismutase (SOD) and catalase activities in the hippocampus of rats during chronic period. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The superoxide dismutase and catalase activities increased during the chronic phase. In addition, lipid peroxidation and nitrite levels increased in same period in the hippocampus of animals observed during spontaneous recurrent seizures. Previous studies showed that animals presenting seizures and submitted to 24h of status epilepticus showed normal levels of superoxide dismutase and increased in catalase activities as well as an increase in hippocampal lipid peroxidation and nitrite concentrations. These results show a direct evidence of lipid peroxidation and nitrite during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of pilocarpine model of epilepsy.

  4. Serotonin receptor 5-HT5A in rat hippocampus decrease by leptin treatment.

    Science.gov (United States)

    García-Alcocer, Guadalupe; Rodríguez, Angelina; Moreno-Layseca, Paulina; Berumen, Laura C; Escobar, Jesica; Miledi, Ricardo

    2010-12-17

    5-Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse receptors subtypes. In this work we studied the changes on the expression of 5-HT(5A) receptors in rat hippocampus induced by leptin, an adipocyte-derived hormone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT(5A) receptor gene expression a qRT-PCR was used and the distribution of those receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and leptin+serotonin treated. The results showed that even though the 5-HT(5A) gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT(5A) serotonin receptor decreased significantly in the dentate gyrus.

  5. Early expression of GABA(A) receptor delta subunit in the neonatal rat hippocampus.

    Science.gov (United States)

    Didelon, F; Mladinic', M; Cherubini, E; Bradbury, A

    2000-12-01

    The cDNA library screening strategy was used to identify the genes encoding for GABA(A) receptor subunits in the rat hippocampus during development. With this technique, genes encoding eleven GABA(A) receptor subunits were identified. The alpha5 subunit was by far the most highly expressed, followed by the gamma2, alpha2 and alpha4 subunits respectively. The expression of the beta2, alpha1, gamma1, beta1 and beta3 subunits was moderate, although that of the alpha3 and delta subunits was weak. In situ hybridization experiments, using digoxigenin-labeled cRNA probes, confirmed that the delta subunit was expressed in the neonatal as well as in the adult hippocampus, and is likely to form functional receptors in association with other subunits of the GABA(A) receptor. When the more sensitive RT-PCR approach was used, the gamma3 subunit was also detected, suggesting that this subunit is present in the hippocampus during development but at low levels of expression. The insertion of the delta subunit into functional GABA(A) receptors may enhance the efficacy of GABA in the immediate postnatal period when this amino acid is still exerting a depolarizing and excitatory action.

  6. Regulation of Astroglia on Synaptic Plasticity in the CA1 Region of Rat Hippocampus

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (<24 h), the juvenile (28-30days) and the adult groups (90-100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively,for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats,and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P<0.01). The cholesterol content was 2.92±0.03 mg/g, 11.20± 3.41 mg/g and 12.91 ± 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P<0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.

  7. Astrocytic Expression of CTMP Following an Excitotoxic Lesion in the Mouse Hippocampus

    Science.gov (United States)

    Shin, Nara; Yi, Min-Hee; Kim, Sena; Baek, Hyunjung; Triantafillu, Ursula L.

    2017-01-01

    Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment. To further investigate the effectiveness of Akt signaling, the phosphorylation of CTMP was examined. KA treatment induced an increased p-CTMP expression in the astrocytes of hippocampus at 1 day. LPS/IFN-γ-treatment on primary astrocytes promoted the p-CTMP was followed by phosphorylation of Akt and finally upregulation of CTMP and p-CREB. Time-dependent expression of p-CTMP, p-Akt, p-CREB, and CTMP indicate that LPS/IFN-γ-induced phosphorylation of CTMP can activate Akt/CREB signaling, whereas lately emerging enhancement of CTMP can inhibit it. These results suggest that elevation of CTMP in the astrocytes may suppress Akt activity and ultimately negatively affect the outcome of astrocyte activation (astroglisiois). Early time point enhancers of phosphorylation of CTMP and/or late time inhibitors specifically targeting CTMP may be beneficial in astrocyte activation for neuroprotection within treatment in neuroinflammatory conditions.

  8. P53 regulates disruption of neuronal development in the adult hippocampus after irradiation

    Science.gov (United States)

    Li, Y-Q; Cheng, ZW-C; Liu, SK-W; Aubert, I; Wong, C S

    2016-01-01

    Inhibition of hippocampal neurogenesis is implicated in neurocognitive dysfunction after cranial irradiation for brain tumors. How irradiation results in impaired neuronal development remains poorly understood. The Trp53 (p53) gene is known to regulate cellular DNA damage response after irradiation. Whether it has a role in disruption of late neuronal development remains unknown. Here we characterized the effects of p53 on neuronal development in adult mouse hippocampus after irradiation. Different bromodeoxyuridine incorporation paradigms and a transplantation study were used for cell fate mapping. Compared with wild-type mice, we observed profound inhibition of hippocampal neurogenesis after irradiation in mice deficient in p53 despite the absence of acute apoptosis of neuroblasts. The putative neural stem cells were apoptosis resistant after irradiation regardless of p53 genotype. Cell fate mapping using different bromodeoxyuridine incorporation paradigms revealed enhanced activation of neural stem cells and their consequential exhaustion in the absence of p53 after irradiation. Both p53-knockout and wild-type mice demonstrated similar extent of microglial activation in the hippocampus after irradiation. Impairment of neuronal differentiation of neural progenitors transplanted in irradiated hippocampus was not altered by p53 genotype of the recipient mice. We conclude that by inhibiting neural progenitor activation, p53 serves to mitigate disruption of neuronal development after irradiation independent of apoptosis and perturbation of the neural stem cell niche. These findings suggest for the first time that p53 may have a key role in late effects in brain after irradiation.

  9. Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior?

    Science.gov (United States)

    Greidanus, T B; De Wied, D

    1976-01-01

    Vasopressin and ACTH 4-10 induce a dose dependent long-term, respectively short-term inhibition of extinction of a pole jumping avoidance response in animals with sham lesions in the antero-dorsal hippocampus. Small lesions, causing a restricted damage in this area of the brain, partly inhibit the behavioral effect of vasopressin. Extensive lesions in the antero-dorsal hippocampus completely prevent the inhibitory effects of vasopressin and of ACTH 4-10 on extinction of the avoidance response. The extensive lesions in the dorsal hippocampus complex do not interfere with the rate of extinction, but acquisition of the response is retarded. These observations do not allow the conclusion that the hippocampal complex is the locus of action of neuropeptides in relation to avoidance behavior; it is more likely that this brain region is but one site of behavioral action of these hormones, and that the limbic system needs to be intact to permit the neuropeptides to exert their behavioral effects.

  10. Goal-oriented searching mediated by ventral hippocampus early in trial-and-error learning.

    Science.gov (United States)

    Ruediger, Sarah; Spirig, Dominique; Donato, Flavio; Caroni, Pico

    2012-11-01

    Most behavioral learning in biology is trial and error, but how these learning processes are influenced by individual brain systems is poorly understood. Here we show that ventral-to-dorsal hippocampal subdivisions have specific and sequential functions in trial-and-error maze navigation, with ventral hippocampus (vH) mediating early task-specific goal-oriented searching. Although performance and strategy deployment progressed continuously at the population level, individual mice showed discrete learning phases, each characterized by particular search habits. Transitions in learning phases reflected feedforward inhibitory connectivity (FFI) growth occurring sequentially in ventral, then intermediate, then dorsal hippocampal subdivisions. FFI growth at vH occurred abruptly upon behavioral learning of goal-task relationships. vH lesions or the absence of vH FFI growth delayed early learning and disrupted performance consistency. Intermediate hippocampus lesions impaired intermediate place learning, whereas dorsal hippocampus lesions specifically disrupted late spatial learning. Trial-and-error navigational learning processes in naive mice thus involve a stereotype sequence of increasingly precise subtasks learned through distinct hippocampal subdivisions. Because of its unique connectivity, vH may relate specific goals to internal states in learning under healthy and pathological conditions.

  11. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression.

    Science.gov (United States)

    Chen, Hao-Hao; Zhang, Ning; Li, Wei-Yun; Fang, Ma-Rong; Zhang, Hui; Fang, Yuan-Shu; Ding, Ming-Xing; Fu, Xiao-Yan

    2015-09-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  12. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Directory of Open Access Journals (Sweden)

    Hao-hao Chen

    2015-01-01

    Full Text Available Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF. In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  13. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hao-hao Chen; Ning Zhang; Wei-yun Li; Ma-rong Fang; Hui Zhang; Yuan-shu Fang; Ming-xing Ding; Xiao-yan Fu

    2015-01-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. ABDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo-campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open ifeld test in these rats as well. These ifndings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  14. Hippocampus activity differentiates good from poor learners of a novel lexicon.

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    Breitenstein, Caterina; Jansen, Andreas; Deppe, Michael; Foerster, Ann-Freya; Sommer, Jens; Wolbers, Thomas; Knecht, Stefan

    2005-04-15

    Language proficiency is a key to academic and workplace success for native and non-native speakers. It is largely unknown, however, why some people pick up languages more easily than others. We used event-related functional magnetic resonance imaging (e-fMRI) to elucidate which brain regions are modulated during the acquisition of a novel lexicon and which of these learning-related activity changes correlated with general semantic language knowledge. Fourteen healthy young subjects learned a novel vocabulary of 45 concrete nouns via an associative learning principle over the course of five blocks during e-fMRI. As a control condition, subjects took part in a structurally identical "No-Learning" condition lacking any learning principle. Overall, increasing vocabulary proficiency was associated with (intercorrelated) modulations of activity within the left hippocampus and the left fusiform gyrus, regions involved in the binding and integration of multimodal stimuli, and with an increasing activation of the left inferior parietal cortex, the presumed neural store of phonological associations. None of these activity changes were observed during the control condition. Furthermore, subjects who showed less suppression of hippocampal activity over learning blocks scored higher on semantic knowledge in their native language and learned the novel vocabulary more efficiently. Our findings indicate that (a) the successful acquisition of a new lexicon depends on correlated amplitude changes between the left hippocampus and neocortical regions and (b) learning-related hippocampus activity is a stable marker of individual differences in the ability to acquire and master vocabularies.

  15. Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus

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    Gislaine Z. Réus

    2010-01-01

    Full Text Available A growing body of evidence has suggested that reactive oxygen species (ROS may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg and imipramine (10, 20 and 30 mg/kg or saline in lipid and protein oxidation levels and superoxide dismutase (SOD and catalase (CAT activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

  16. Effect of Protein Malnutrition on Efferent Projections of Amygdala to the Hippocampus

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    Gholamreza Hassanzadeh

    2010-11-01

    Full Text Available ABSTRACTIntroduction: Previous investigations have shown that protein malnutrition can alters the structure and function of some areas of hippocampal formation. We investigated the effect of protein malnutrition on amygdaloid projections to the CA1 hippocampal area. In this study we investigated level and pattern of distribution of efferent projections from amygdala to hippocampus in the rat by Horseradish Peroxidas (HRP neural tract tracing in 2 groups; Control group fed with regular diet (% 18 proteinsand case group fed with low protein diet (%8. We used SPSS 11.0 (T test & mann-withney Software for data analysis.Methods: Following injection of HRP to CA1 region of hippocampus in the control group Rats, Labelled neurons showed more density in the Basolateral, Cortical and Medial nuclear Groups. Having done the analysis and examining the relations between the case data and those of the control groups, we found that number of labelled neurons in the Basolateral, Cortical & medial nuclei were decreased in the case group(p<0.05. Our findings showed that different nuclei of amygdala (Basolateral, Cortical and Medial send projections to CA1 region of hippocampus; Among, them basolateral nuclei group send the most projections . Discussion: This results may be caused by decrease of activity of neural cells after protein malnutrition, that can results in impairment in growth and development of nervous system. Also it is possible that axoplasmic transfer rate maybe decreased in this condition.

  17. The Timing for Neuronal Maturation in the Adult Hippocampus Is Modulated by Local Network Activity

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    Piatti, Verónica C.; Davies-Sala, M. Georgina; Espósito, M. Soledad; Mongiat, Lucas A.; Trinchero, Mariela F.; Schinder, Alejandro F.

    2013-01-01

    The adult hippocampus continuously generates new cohorts of immature neurons with increased excitability and plasticity. The window for the expression of those unique properties in each cohort is determined by the time required to acquire a mature neuronal phenotype. Here, we show that local network activity regulates the rate of maturation of adult-born neurons along the septotemporal axis of the hippocampus. Confocal microscopy and patch-clamp recordings were combined to assess marker expression, morphological development, and functional properties in retrovirally labeled neurons over time. The septal dentate gyrus displayed higher levels of basal network activity and faster rates of newborn neuron maturation than the temporal region. Voluntary exercise enhanced network activity only in the temporal region and, in turn, accelerated neuronal development. Finally, neurons developing within a highly active environment exhibited a delayed maturation when their intrinsic electrical activity was reduced by the cell-autonomous overexpression of Kir2.1, an inward-rectifying potassium channel. Our findings reveal a novel type of activity-dependent plasticity acting on the timing of neuronal maturation and functional integration of newly generated neurons along the longitudinal axis of the adult hippocampus. PMID:21613484

  18. Differential proliferation rhythm of neural progenitor and oligodendrocyte precursor cells in the young adult hippocampus.

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    Yoko Matsumoto

    Full Text Available Oligodendrocyte precursor cells (OPCs are a unique type of glial cells that function as oligodendrocyte progenitors while constantly proliferating in the normal condition from rodents to humans. However, the functional roles they play in the adult brain are largely unknown. In this study, we focus on the manner of OPC proliferation in the hippocampus of the young adult mice. Here we report that there are oscillatory dynamics in OPC proliferation that differ from neurogenesis in the subgranular zone (SGZ; the former showed S-phase and M-phase peaks in the resting and active periods, respectively, while the latter only exhibited M-phase peak in the active period. There is coincidence between different modes of proliferation and expression of cyclin proteins that are crucial for cell cycle; cyclin D1 is expressed in OPCs, while cyclin D2 is observed in neural stem cells. Similar to neurogenesis, the proliferation of hippocampal OPCs was enhanced by voluntary exercise that leads to an increase in neuronal activity in the hippocampus. These data suggest an intriguing control of OPC proliferation in the hippocampus.

  19. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

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    Farzaneh Bagheri-abassi

    2015-07-01

    Full Text Available Objective(s:Silver nanoparticles (Ag-NPs are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods:12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group. Animals in the experimental group received Ag-NPs (30 mg/kg orally (gavage for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs and apoptotic neurons were counted by morphometric method. Results: Results showed that the num­bers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P

  20. Parvalbumin-positive GABAergic interneurons are increased in the dorsal hippocampus of the dystrophic mdx mouse.

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    Del Tongo, Claudia; Carretta, Donatella; Fulgenzi, Gianluca; Catini, Claudio; Minciacchi, Diego

    2009-12-01

    Duchenne muscular dystrophy (DMD) is characterized by variable alterations of the dystrophin gene and by muscle weakness and cognitive impairment. We postulated an association between cognitive impairment and architectural changes of the hippocampal GABAergic system. We investigated a major subpopulation of GABAergic neurons, the parvalbumin-immunopositive (PV-I) cells, in the dorsal hippocampus of the mdx mouse, an acknowledged model of DMD. PV-I neurons were quantified and their distribution was compared in CA1, CA2, CA3, and dentate gyrus in wild-type and mdx mice. The cell morphology and topography of PV-I neurons were maintained. Conversely, the number of PV-I neurons was significantly increased in the mdx mouse. The percent increase of PV-I neurons was from 45% for CA2, up to 125% for the dentate gyrus. In addition, the increased parvalbumin content in the mdx hippocampus was confirmed by Western blot. A change in the hippocampus processing abilities is the expected functional counterpart of the modification displayed by PV-I GABAergic neurons. Altered hippocampal functionality can be responsible for part of the cognitive impairment in DMD.

  1. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

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    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations.

  2. Ablation of BRaf impairs neuronal differentiation in the postnatal hippocampus and cerebellum.

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    Verena Pfeiffer

    Full Text Available This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12 but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.

  3. Functional inactivation of the rat hippocampus disrupts avoidance of a moving object.

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    Telensky, Petr; Svoboda, Jan; Blahna, Karel; Bureš, Jan; Kubik, Stepan; Stuchlik, Ales

    2011-03-29

    The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 μL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8). No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.

  4. Cloning and Identification of Novel MicroRNAs from Rat Hippocampus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    MicroRNAs (miRNAs) are small regulatory molecules post-transcriptionally suppressing mRNA activity. Many miRNAs in various organisms have been cloned but many unknown miRNAs remain to be identified. Here we describe the cloning of six new miRNAs from rat hippocampus. Among them, four were not found in the rat miRBase, but were identical to their human and/or mouse homolog, therefore they were designated as rno-miR-92b, rno-miR-146b, rno-let-7g, and rno-miR-551b. The other two were derived from the other arms of the known miRNA precursors of rno-miR-330 and rno-miR-384, and were not found in miRBase of all organisms. They were designated as rno-miR-330* and rno-miR-384*. The expression of these miRNAs was confirmed by RNA-tailing and primer-extension real-time reverse transcriptionpolymerase chain reaction. These six miRNAs were expressed at significantly higher levels in the hippocampus than in other tissues, including cerebral cortex, heart, liver, lung and kidney. miR-384* was 10 times more abundant than miR-384 in rat hippocampus, but little difference was found between miR-330* and miR-330 expression in the same tissue.

  5. Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens.

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    Dong, Zhifang; Han, Huili; Wang, Meina; Xu, Lin; Hao, Wei; Cao, Jun

    2006-01-01

    Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus and nucleus accumbens (NAc). The underlying mechanisms are not fully understood. Here, we examined whether glucocorticoid receptors (GRs) of hippocampus and NAc influenced the formation of morphine CPP in Sprague Dawley rats. We found that systemic or intrahippocampal infused DMSO vehicle (DMSO 20% in saline) 30 min before daily morphine (10 mg/kg, s.c.) conditioning did not affect the formation of morphine CPP. In contrast, systemic administration (5 mg/kg, s.c.) or intrahippocampal infusion (0, 0.1, 1.0, 10, 20 microg per side) of the GR antagonist RU38486 blocked or impaired the formation of CPP in a dose-dependent manner, respectively. Furthermore, intra-NAc infused RU38486 (10 microg per side) but not DMSO vehicle also prevented the formation of CPP. These results demonstrate that both the GRs of hippocampus and NAc are necessary for the formation of morphine CPP, suggesting a neural network function of the GRs in forming the opiate-associated memory.

  6. Morphine and yohimbine regulate midkine gene expression in the rat hippocampus.

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    Ezquerra, Laura; Pérez-García, Carmen; Garrido, Elisa; Díez-Fernández, Carmen; Deuel, Thomas F; Alguacil, Luis F; Herradón, Gonzalo

    2007-02-28

    Pleiotrophin and midkine are two recently discovered growth factors that promote survival and differentiation of catecholaminergic neurons. Chronic opioid stimulation has been reported to induce marked alterations of the locus coeruleus-hippocampus noradrenergic pathway, an effect that is prevented when opioids are coadministered with the alpha2-adrenoceptor antagonist yohimbine. The present work tries to examine a possible link between yohimbine reversal of morphine effects and pleiotrophin/midkine activation in the rat hippocampus by studying the levels of expression of pleiotrophin and midkine in response to acute and chronic administration of morphine, yohimbine and combinations of both drugs. Pleiotrophin gene expression was not altered by any treatment; however midkine mRNA levels were increased after chronic treatment with morphine. Chronic administration of yohimbine alone also increased midkine expression levels, whereas yohimbine and morphine administered together exhibited summatory effects on the upregulation of midkine expression levels. The data suggest that midkine could play a role in the prevention of opioid-induced neuroadaptations in hippocampus by yohimbine.

  7. The effect of morphine sensitization on extracellular concentrations of GABA in dorsal hippocampus of male rats.

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    Farahmandfar, Maryam; Zarrindast, Mohammad-Reza; Kadivar, Mehdi; Karimian, Seyed Morteza; Naghdi, Nasser

    2011-11-01

    Repeated, intermittent exposure to drugs of abuse, such as morphine results in response enhancements to subsequent drug treatments, a phenomenon referred to as behavioral sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neurochemical mechanisms of sensitization is providing insights into addiction. Although it has been shown that GABAergic systems in the CA1 region of dorsal hippocampus are involved in morphine sensitization, the alteration of extracellular level of GABA in this area in morphine sensitization has not been investigated. In the present study, using the in vivo microdialysis technique, we investigated the effect of morphine sensitization on extracellular GABA concentration in CA1 region of dorsal hippocampus of freely moving rats. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular GABA concentration in CA1 was decreased following acute administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular GABA concentration in this area. The enhancement of GABA in morphine sensitized rats was inhibited by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the GABAergic neuronal transmission in dorsal hippocampus induced by morphine sensitization and it is implied that opioid receptors may play an important role in this effect.

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

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    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.

  9. Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Cai; Libai Yang; Jueqian Zhou; Dan Zhu; Qiang Guo; Ziyi Chen; Shuda Chen; Liemin Zhou

    2013-01-01

    The Na+-K+-Cl– cotransporter 1 and K+-Cl– cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of Cl– homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na+-K+-Cl– cotransporter 1 and K+-Cl– cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na+-K+-Cl– cotransporter 1 expression and decreased K+-Cl– cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na+-K+-Cl– cotransporter 1 than for the K+-Cl– cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na+-K+-Cl– cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

  10. Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders.

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    Kaymak, Semra Ulusoy; Demir, Başaran; Sentürk, Senem; Tatar, Ilkan; Aldur, M Mustafa; Uluğ, Berna

    2010-04-01

    The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

  11. Effects of carbon disulfide on the expression and activity of nitric oxide synthase in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Carbon disulfide (CS2) is a commonly used organic solvent. Many epidemiological investigations and animal experiments have indicated that learning and memory ability can be affected to different degrees after long-term exposure to CS2, but the mechanisms are still unclear. The aim of this study was to explore the possible mechanisms of CS2-related impairment of the learning and memory ability of rats, by investigating the effects of CS2 on nitric oxide synthase (NOS) activity and NOS mRNA expression in rat hippocampus. Methods Rat models of toxicity were generated by inhalation of various doses of CS2. After two months of inhaling intoxication, the activities of constitutive NOS (cNOS) and induced NOS (iNOS) in the hippocampus were measured. The levels of neuronal NOS (nNOS) mRNA and iNOS mRNA were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results cNOS activity was significantly decreased compared with controls, while iNOS activity was changed only slightly. CS2 treatment significantly decreased nNOS mRNA levels, iNOS mRNA levels were significantly increased only at higher doses of CS2. Conclusion The effect of CS2 on learning and memory ability in rats is related to the activity of NOS and the expression of nNOS in the hippocampus.

  12. Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.

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    Wang, Lai; Wu, Lin; Wang, Xiaoqing; Deng, Jiexin; Ma, Zhanyou; Fan, Wenjuan; He, Weiya; Deng, Jinbo

    2015-11-01

    In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (palcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (palcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (palcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.

  13. The similarity of astrocytes number in dentate gyrus and CA3 subfield of rats hippocampus.

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    Jahanshahi, Mehrdad; Sadeghi, Y; Hosseini, A; Naghdi, N

    2007-01-01

    The dentate gyrus is a part of hippocampal formation that it contains granule cells, which project to the pyramidal cells and interneurons of the CA3 subfield of the hippocampus. Astrocytes play a more active role in neuronal activity, including regulating ion flux currents, energy production, neurotransmitter release and synaptogenesis. Astrocytes are the only cells in the brain that contain the energy molecule glycogen. The close relationship between dentate gyrus and CA3 area can cause the similarity of the number of astrocytes in these areas. In this study 5 male albino wistar rats were used. Rats were housed in large plastic cage in animal house and were maintained under standard conditions, after histological processing, The 7 microm slides of the brains were stained with PTAH staining for showing the astrocytes. This staining is specialized for astrocytes. We showed that the number of astrocytes in different (ant., mid., post) parts of dentate gyrus and CA3 of hippocampus is the same. For example, the anterior parts of two area have the most number of astrocytes and the middle parts of two area have the least number of astrocytes. We concluded that dentate gyrus and CA3 area of hippocampus have the same group of astrocytes.

  14. EFFECT OF EXERCISE ON LEARNING, MEMORY AND LEVELS OF EPINEPHRINE IN RATS' HIPPOCAMPUS

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    Hojjatallah Alaei

    2003-09-01

    Full Text Available The aim of the present study was to investigate effect of exercise on learning and memory, long-term potentiation and levels of epinephrine in the rat hippocampus. Treadmill trained (one hour at 17 m·min-1 for 10 days and corresponding control rats went through spatial learning process on a Morris water maze for 8 days. The time to reach the platform (latency, the length of swim path, and the swim speed were used for the evaluation of spatial learning. Our results showed that physical activity produced a significant enhancement in spatial learning, with a decreased path length (p<0.05 and latency (p<0.05 to the platform in Morris water maze, without affecting the swim speed. Furthermore, the levels of the epinephrine were significantly increased (p<0.05 in hippocampus of the exercised rats. In conclusion our findings suggest that the enhanced learning by exercise may be mediated through the activation of adrenoceptors in the hippocampus and epinephrine may play an important role in potentiation of learning

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

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    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.

  16. 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.

  17. Structural organization of long-range GABAergic projection system of the hippocampus

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    Shozo Jinno

    2009-07-01

    Full Text Available GABA is a key mediator of neural activity in the mammalian central nervous system, and a diverse set of GABAergic neurons utilize GABA as transmitter. It has been widely accepted that GABAergic neurons typically serve as interneurons while glutamatergic principal cells send excitatory signals to remote areas. In general, glutamatergic projection neurons monosynaptically innervate both principal cells and local GABAergic interneurons in each target area, and these GABAergic cells play a vital role in modulation of the activity of principal cells. The formation and recall of sensory, motor and cognitive representations require coordinated fast communication among multiple areas of the cerebral cortex, which are thought to be mostly mediated by glutamatergic neurons. However, there is an increasing body of evidence showing that specific subpopulations of cortical GABAergic neurons send long-range axonal projections to subcortical and other cortical areas. In particular, a variety of GABAergic neurons in the hippocampus project to neighboring and remote areas. Using anatomical, molecular and electrophysiological approaches, several types of GABAergic projection neurons have been shown to exist in the hippocampus. The target areas of these cells are the subiculum and other retrohippocampal areas, the medial septum and the contralateral dentate gyrus. The long-range GABAergic projection system of the hippocampus may serve to coordinate precisely the multiple activity patterns of widespread cortical cell assemblies in different brain states and among multiple functionally related areas.

  18. Structural impairments of hippocampus in coal mine gas explosion-related posttraumatic stress disorder.

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    Zhang, Quan; Zhuo, Chuanjun; Lang, Xu; Li, Huabing; Qin, Wen; Yu, Chunshui

    2014-01-01

    Investigations on hippocampal and amygdalar volume have revealed inconsistent results in patients with posttraumatic stress disorder (PTSD). Little is known about the structural covariance alterations between the hippocampus and amygdala in PTSD. In this study, we evaluated the alteration in the hippocampal and amygdalar volume and their structural covariance in the coal mine gas explosion related PTSD. High resolution T1-weighted magnetic resonance imaging (MRI) was performed on coal mine gas explosion related PTSD male patients (n = 14) and non-traumatized coalminers without PTSD (n = 25). The voxel-based morphometry (VBM) method was used to test the inter-group differences in hippocampal and amygdalar volume as well as the inter-group differences in structural covariance between the ipsilateral hippocampus and amygdala. PTSD patients exhibited decreased gray matter volume (GMV) in the bilateral hippocampi compared to controls (pexplosion related PTSD had decreased hippocampal volume and structural covariance with the ipsilateral amygdala, suggesting that the structural impairment of the hippocampus may implicate in the pathophysiology of PTSD.

  19. The hippocampus and inferential reasoning: building memories to navigate future decisions.

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    Zeithamova, Dagmar; Schlichting, Margaret L; Preston, Alison R

    2012-01-01

    A critical aspect of inferential reasoning is the ability to form relationships between items or events that were not experienced together. This review considers different perspectives on the role of the hippocampus in successful inferential reasoning during both memory encoding and retrieval. Intuitively, inference can be thought of as a logical process by which elements of individual existing memories are retrieved and recombined to answer novel questions. Such flexible retrieval is sub-served by the hippocampus and is thought to require specialized hippocampal encoding mechanisms that discretely code events such that event elements are individually accessible from memory. In addition to retrieval-based inference, recent research has also focused on hippocampal processes that support the combination of information acquired across multiple experiences during encoding. This mechanism suggests that by recalling past events during new experiences, connections can be created between newly formed and existing memories. Such hippocampally mediated memory integration would thus underlie the formation of networks of related memories that extend beyond direct experience to anticipate future judgments about the relationships between items and events. We also discuss integrative encoding in the context of emerging evidence linking the hippocampus to the formation of schemas as well as prospective theories of hippocampal function that suggest memories are actively constructed to anticipate future decisions and actions.

  20. The hippocampus and inferential reasoning: Building memories to navigate future decisions

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    Dagmar eZeithamova

    2012-03-01

    Full Text Available A critical aspect of inferential reasoning is the ability to form a relationship between items or events that were not experienced together. This review will consider different perspectives on the role of the hippocampus in successful inferential reasoning. Traditional research on inferential reasoning has focused on retrieval-based processes that mediate performance. To make inferences about indirect relationships between discrete events, elements of individual memories must be individually retrieved and recombined. Specialized encoding mechanisms are needed to enable this flexible retrieval. The hippocampus has been shown to discretely code events in such a way that event elements are individually accessible from memory. For this reason, recent research has also focused on hippocampal encoding processes that support inferential reasoning, including an integrative mechanism that combines information across multiple experiences. By recalling past events during the encoding of new experiences, connections can be created between newly formed and existing memories. Such derived memories extend beyond direct experience to anticipate future judgments about the relationship between items and events. Successful inference, according to this view, would result from the expression of relational knowledge acquired through hippocampally-mediated integrative encoding. We discuss this latter perspective in the context of emerging evidence linking the hippocampus to the formation of schemas as well as prospective theories of hippocampal function that suggest memories are actively constructed to anticipate future decisions and actions.

  1. Antioxidant effects of nerolidol in mice hippocampus after open field test.

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    Nogueira Neto, José Damasceno; de Almeida, Antonia Amanda Cardoso; da Silva Oliveira, Johanssy; Dos Santos, Pauline Sousa; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2013-09-01

    The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

  2. Differential patterns of myosin Va expression during the ontogenesis of the rat hippocampus

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    L.S. Brinn

    2010-09-01

    Full Text Available Myosin Va is an actin-based, processive molecular motor protein highly enriched in the nervous tissue of vertebrates. It has been associated with processes of cellular motility, which include organelle transport and neurite outgrowth. The in vivo expression of myosin Va protein in the developing nervous system of mammals has not yet been reported. We describe here the immunolocalization of myosin Va in the developing rat hippocampus. Coronal sections of the embryonic and postnatal rat hippocampus were probed with an affinity-purified, polyclonal anti-myosin Va antibody. Myosin Va was localized in the cytoplasm of granule cells in the dentate gyrus and of pyramidal cells in Ammon's horn formation. Myosin Va expression changed during development, being higher in differentiating rather than already differentiated granule and pyramidal cells. Some of these cells presented a typical migratory profile, while others resembled neurons that were in the process of differentiation. Myosin Va was also transiently expressed in fibers present in the fimbria. Myosin Va was not detected in germinative matrices of the hippocampus proper or of the dentate gyrus. In conclusion, myosin Va expression in both granule and pyramidal cells showed both position and time dependency during hippocampal development, indicating that this motor protein is under developmental regulation.

  3. Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory.

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    Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui; Li, Tan; Abel, Glen M; Palmiter, Richard D; Storm, Daniel R; Xia, Zhengui

    2014-02-05

    Recent studies have shown that inhibition of adult neurogenesis impairs the formation of hippocampus-dependent memory. However, it is not known whether increasing adult neurogenesis affects the persistence of hippocampus-dependent long-term memory. Furthermore, signaling mechanisms that regulate adult neurogenesis are not fully defined. We recently reported that the conditional and targeted knock-out of ERK5 MAP kinase in adult neurogenic regions of the mouse brain attenuates adult neurogenesis in the hippocampus and disrupts several forms of hippocampus-dependent memory. Here, we developed a gain-of-function knock-in mouse model to specifically activate endogenous ERK5 in the neurogenic regions of the adult brain. We report that the selective and targeted activation of ERK5 increases adult neurogenesis in the dentate gyrus by enhancing cell survival, neuronal differentiation, and dendritic complexity. Conditional ERK5 activation also improves the performance of challenging forms of spatial learning and memory and extends hippocampus-dependent long-term memory. We conclude that enhancing signal transduction of a single signaling pathway within adult neural stem/progenitor cells is sufficient to increase adult neurogenesis and improve the persistence of hippocampus-dependent memory. Furthermore, activation of ERK5 may provide a novel therapeutic target to improve long-term memory.

  4. Formaldehyde impairs learning and memory involving the disturbance of hydrogen sulfide generation in the hippocampus of rats.

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    Tang, Xiao-Qing; Zhuang, Yuan-Yuan; Zhang, Ping; Fang, Heng-Rong; Zhou, Cheng-Fang; Gu, Hong-Feng; Zhang, Hui; Wang, Chun-Yan

    2013-01-01

    Formaldehyde (FA), a well-known indoor and outdoor pollutant, has been implicated as the responsible agent in the development of neurocognitive disorders. Hydrogen sulfide (H(2)S), the third gasotransimitter, is an endogenous neuromodulator, which facilitates the induction of hippocampal long-term potentiation, involving the functions of learning and memory. In the present study, we analyzed the effects of intracerebroventricular injection of FA on the formation of learning and memory and the generation of endogenous H(2)S in the hippocampus of rats. We found that the intracerebroventricular injection of FA in rats impairs the function of learning and memory in the Morris water maze and novel object recognition test and increases the formation of apoptosis and lipid peroxidation in the hippocampus. We also showed that FA exposure inhibits the expression of cystathionine β-synthase, the major enzyme responsible for endogenous H(2)S generation in hippocampus and decreases the production of endogenous H(2)S in hippocampus in rats. These results suggested that FA-disturbed generation of endogenous H(2)S in hippocampus leads to the oxidative stress-mediated neuron damage, ultimately impairing the function of learning and memory. Our findings imply that the disturbance of endogenous H(2)S generation in hippocampus is a potential contributing mechanism underling FA-caused learning and memory impairment.

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

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    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.

  6. ISCHEMIC PRECONDITIONING RELIEVES ISCHEMIA/REPERFUSION INJURY OF HIPPOCAMPUS NEURONS IN RAT BY INHIBITING p53 AND BAX EXPRESSIONSA

    Institute of Scientific and Technical Information of China (English)

    Hui-min Liu; Jing-xin Li; Lian-bi Chen

    2007-01-01

    Objective To examine whether ischemic preconditioning (IPC) can protect neuron against delayed death in CA1 subfield of hippocampus following reperfusion of a lethal ischemia in rats, and explore the role of p53 and bax in this process.Methods We examined the effect of IPC on delayed neuron death, neuron apoptosis, expressions of p53 and bax gene in the CA1 area of hippocampus in the rats using HE staining, flow cytometry, RT-PCR, and immunohistochemis-try technique.Results IPC enhanced the quantity of survival cells in the CA1 region of hippocampus (216 ±9 cells/0. 72 mm2 vs. 30 ±5 cells/0. 72 mm2, P<0. 01), decreased the percentages of apoptotic neurons of hippocampus caused by is-chemia/reperfusion (2. 06% ±0.21% vs. 4.27% ±0. 08% , P<0. 01), and weakened the expressions of p53 and bax gene of hippocampus compared with ischemia/reperrusion without IPC.Conclusion IPC can protect the neurons in the CA1 region of hippocampus against apoptosis caused by ischemia/reperfusion, and this process may be related to the reduced expressions of p53 and bax.

  7. Region-specific upregulation of parvalbumin-, but not calretinin-positive cells in the ventral hippocampus during adolescence.

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    Caballero, Adriana; Diah, Kimberly C; Tseng, Kuei Y

    2013-12-01

    Animal studies have highlighted the role of the ventral hippocampus-prefrontal cortex pathway in the acquisition of mature cortical function through refinement of GABAergic circuits during adolescence. Inhibitory GABAergic responses are mediated by highly specialized interneurons, which have distinct functional properties and are characterized by the expression of calcium binding proteins. Among these, we recently found that parvalbumin (PV)- and calretinin (CR)-positive interneurons in the prefrontal cortex follow opposite developmental trajectories during the periadolescent transition period. In the present study, we asked whether interneurons expressing PV and CR in the ventral hippocampus follow similar periadolescent trajectories as seen in the prefrontal cortex. By measuring the relative abundance of these interneurons in three age groups (postnatal days (PD) 25-40, 45-55, and 60-85), we found that regions within the dorso-ventral axis of the ventral hippocampus undergo distinct developmental trajectories in PV expression during the periadolescent transition. Specifically, the ventral subiculum displayed a dramatic increase in PV-positive interneurons from PD25-40 to PD45-55 with an increasing rostro-caudal gradient, whereas negligible changes were found in the dorsal and middle regions. In contrast, the number of CR-positive interneurons in the ventral hippocampus remained unchanged across the three age groups studied. Together, these results describe for the first time that GABAergic circuits in the ventral hippocampus undergo protracted development during adolescence, in particular the PV-positive cell population circumscribed to the ventral region of the ventral hippocampus.

  8. Studies of the macroscopic and microscopic morphology (hippocampus of brain in Vencobb broiler

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    Shailesh Kumar Gupta

    2016-05-01

    Full Text Available Aim: The aim of this study was to study the anatomy of different parts of brain and histology of hippocampus of Vencobb broiler chicken. Materials and Methods: A 12 adult experimental birds were sacrificed by cervical dislocation. After separation of the brain, gross anatomy features were studied. Brain tissue was fixed in 10% buffered neutral formalin for 2-3 days, and then routine dehydration process in ascending grades of ethyl alcohol was done. After xylene cleaning, paraffin impregnation was prepared. Paraffin blocks were cut, and slides were stained by Harris hematoxylin and eosin. Photography was carried out both under lower (×10 and higher (×40 magnifications. Results: The brain structure (dorsal view of Vencobb bird resembled the outline of a playing card symbol of a “spade.” The brain subdivisions are cerebrum, cerebellum, and medulla oblongata. Cerebrum was devoid of usual convolutions (elevations, gyri, depressions (grooves, and sulci. The cerebral hemispheres were tightly apposed along a median sulcus called interhemispheric fissure and cerebrum and cerebellum were separated by a small transverse fissure. The olfactory bulb was small structures, and the pineal body was clearly visible. The optic lobes were partially hidden under cerebral hemispheres, but laterally, it was large, prominent rounded or spherical bodies of the midbrain. The hippocampal area appeared as dorso-medial protrusion. Different types of neurons were distinguished in the hippocampus were pyramidal neurons, pyramidal-like neurons, and multipolar neurons, etc. There was rich vascularization in the form of blood capillaries throughout the hippocampus. Conclusion: Cerebrum was pear shaped and largest part of the brain. Cerebrum hemisphere was smooth devoid of convolutions, gyri, and depressions, but in the surface of cerebellum, there was the presence of a number of transverse depression (grooves and sulci subdividing into many folds. Olfactory bulb was poorly

  9. Parallel processing of information about location in the amygdala, entorhinal cortex and hippocampus.

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    Gaskin, Stephane; White, Norman M

    2013-11-01

    The conditioned cue preference paradigm was used to study how rats use extra-maze cues to discriminate between 2 adjacent arms on an 8-arm radial maze, a situation in which most of the same cues can be seen from both arms but only one arm contains food. Since the food-restricted rats eat while passively confined on the food-paired arm no responses are reinforced, so the discrimination is due to Pavlovian stimulus-reward (or outcome) learning. Consistent with other evidence that rats must move around in an environment to acquire a spatial map, we found that learning the adjacent arms CCP (ACCP) required a minimum amount of active exploration of the maze with no reinforcers present prior to passive pairing of the extra-maze cues with the food reinforcer, an instance of latent learning. Temporary inactivation of the hippocampus during the pre-exposure sessions had no effect on ACCP learning, confirming other evidence that the hippocampus is not involved in latent learning. A series of experiments indentified a circuit involving fimbria-fornix and dorsal entorhinal cortex as the neural basis of latent learning in this situation. In contrast, temporary inactivation of the entorhinal cortex or hippocampus during passive training or during testing blocked ACCP learning and expression, respectively, suggesting that these two structures co-operate in using spatial information to learn the location of food on the maze during passive pairing and to express this combined information during testing. In parallel with these processes we found that the amygdala processes information leading to an equal tendency to enter both adjacent arms (even though only one was paired with food) suggesting that the stimulus information available to this structure is not sufficiently precise to discriminate between the ambiguous cues visible from the adjacent arms. Expression of the ACCP in normal rats depends on hippocampus-based learning to avoid the unpaired arm which competes with the

  10. Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin.

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    Himeda, Toshiki; Hayakawa, Natsumi; Tounai, Hiroko; Sakuma, Mio; Kato, Hiroyuki; Araki, Tsutomu

    2005-11-01

    We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV- and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV- and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can

  11. METALS IN THE METABOLISM OF HIPPOCAMPUS AND ROLE OF ZINC IN THE PATHOGENESIS OF EPILEPTIC SEIZURES

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    O. M. Kuchkovsky

    2016-05-01

    Full Text Available Physiological mechanisms of convulsions status during epilepsy or episindrom significantly different from the mechanisms, which were describe for other disorders associated with glutamatergic system, such as schizophrenia (a decrease of glutamate in neurons and increased dopaminergic load, drug addiction and alcoholism (the formation of endogenous opioids and dopamine, strengthening the role of GABA-ergic system. With glutamatergic transmission are сconnect not only convulsive state, but also the realization of higher integrative functions. Therefore, the development of epilepsy, particularly  which caused glutamate, implemented by activating Zn-ergic hippocampal neurons, associate with complex changes in human mental functions. Based on a scientific literature about  of the role of chelating zinc in the mechanisms of glutamatergic transmission, we can  suggest it participation in the mechanisms of formation of epilepsy  convulsions. In experience on animals, was show that in the animal organism of stressing correlative changes observe zinc content and secretory material in the hippocampus, Paneth cells  and B cells of pancreas. The nature of the changes depend on the stressor. When this change of zinc content in the hippocampus and hypothalamus (as the main regulator of stress reaction were multidirectional that this can be explained by the release of metal together with secretory material in the hypothalamus into the bloodstream. Research epileptic activity  of hippocampus by administering to the animal chelate 8 BSQ allowed to establish the dependence between convulsant action  and first  stress condition of the animal. Evocation of stress by 8-BSQ and physical activity, immobilization and alcohol abuse found that the convulsive effect of this reagent during intravitreal research increased in the case of prior exposure by specified kinds of stressors. In this pre-convulsive effect on exertion increased by 266% and the zinc content

  12. Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

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    Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

    2015-02-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical

  13. The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus.

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    Ichihashi, Yukiko; Saito, Naonori; Arakawa, Yoko; Kurata, Chika; Iinuma, Mitsuo; Tamura, Yasuo; Iwaku, Fumihiko; Kubo, Kin-Ya

    2008-02-01

    In the present study, we examined whether the effects induced by the bite-raised condition on glucocorticoid receptor (GR) expression differ between the dorsal and ventral hippocampus in SAMP8 mice. In the bite-raised condition, the number of GR-immunoreactive cells was significantly decreased in both the dorsal and ventral CA1 and dentate gyrus (DG) subfields of the hippocampus compared to control mice, as revealed by immunohistochemical analysis. The decrease in the number of GR-immunoreactive cells tended to be greater in the dorsal hippocampus than in the ventral hippocampus. Only in the DG subfield was there a significant difference in the number of GR-immunoreactive cells between the dorsal and ventral hippocampus. These findings suggest that in aged SAMP8 mice, the bite-raised condition decreases the number of GR-immunoreactive cells in both the dorsal and ventral hippocampus.

  14. Differential role of the dorsal hippocampus, ventro-intermediate hippocampus, and medial prefrontal cortex in updating the value of a spatial goal.

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    De Saint Blanquat, Paul; Hok, Vincent; Save, Etienne; Poucet, Bruno; Chaillan, Franck A

    2013-05-01

    Encoding of a goal with a specific value while performing a place navigation task involves the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC), and depends on the coordination between mPFC and the ventro-intermediate hippocampus (vHPC).The present work investigates the contribution of mPFC, dHPC, and vHPC when the rat has to update the value of a goal. Rats were trained to navigate to an uncued goal in order to release a food pellet in a continuous place navigation task. When they had reached criterion performance level in the task, they were subjected to a single "flash session" in which they were exposed to an aversive strobe light during goal visits instead of receiving a food reward. Just before the flash session, the GABA(A) agonist muscimol was injected to temporarily inactivate mPFC, dHPC, or vHPC. The ability to recall the changed value of the goal was tested on the next day. We first demonstrate the aversive effect of the strobe light by showing that rats learn to avoid the goal much more rapidly in the flash session than during a simple extinction session in which goal visits are not rewarded. Furthermore, while dHPC inactivation had no effect on learning and recalling the new goal value, vHPC muscimol injections considerably delayed goal value updating during the flash session, which resulted in a slight deficit during recall. In contrast, mPFC muscimol injections induced faster goal value updating but the rats were markedly impaired on recalling the new goal value on the next day. These results suggest that, contrary to mPFC and dHPC, vHPC is required for updating the value of a goal. In contrast, mPFC is necessary for long-term retention of this updating.

  15. 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.

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

    Science.gov (United States)

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

    2014-11-19

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

  17. Kepadatan Sel Hipokampus Insulin Imunoreaktif pada Formasi Hipokampus Mencit yang Diinduksi Berulang dengan Streptozotosin (THE DENSITY OF HIPPOCAMPUS INSULIN IMMUNOREACTIVE CELLS IN HIPPOCAMPUS FORMATION OF REPEAT STREPTOZOSIN INDUCED MICE

    Directory of Open Access Journals (Sweden)

    Erwin .

    2013-09-01

    Full Text Available The presence of insulin in the hippocampus may indicate its involvement in brain cognitive function,such as learning and memory phenomena. The purpose of this study was to find out the density ofhippocampus insulin immunoreactive cells in hippocampus formation in Balb-C mice which treated withstreptozosin repeated as the animal model of diabetes mellitus. Thirty male mice Balb-C strain, aged 12-14 weeks, weight 30-40 g, divided into 2 treatment groups, each group consisted of 15 individuals. GroupI (KI was treated with sodium citrate buffer, while group II (K2 was treated with streptozotosin at  dose0,5 ml of 40 mg/kg bw in 50 mM sodium citrate buffer pH 4.5 in intra-peritoneal of for five consecutive days.Every two animals from each group euthanasia and necropsied on day 7, 14, 21 and 28 respectively afterthe administration of treatment. Subsequently, the brain tissues were collected and fixatived in NBF10%. Brain sampel were the processed immunohistochemically using anti-insulin mouse antibody. Thedensity of hippocampus insulin immunoreactive cells in hippocampus formation in group 1 were highercompared to group 2. This comparasion as well as the time of observation and interaction between groupand time showed significant differences (p<0.05. it can be concluded that low-dose induction of repeatedstreptozotosin may  cause a decrease in density of hippocampus insulin imunoreaktif cell.

  18. Neuropathologic features in the hippocampus and cerebellum of three older men with fragile X syndrome

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    Greco Claudia M

    2011-02-01

    Full Text Available Abstract Background Fragile X syndrome (FXS is the most common inherited form of intellectual disability, and is the most common single-gene disorder known to be associated with autism. Despite recent advances in functional neuroimaging and our understanding of the molecular pathogenesis, only limited neuropathologic information on FXS is available. Methods Neuropathologic examinations were performed on post-mortem brain tissue from three older men (aged 57, 64 and 78 years who had received a clinical or genetic diagnosis of FXS. In each case, physical and cognitive features were typical of FXS, and one man was also diagnosed with autism. Guided by reports of clinical and neuroimaging abnormalities of the limbic system and cerebellum of individuals with FXS, the current analysis focused on neuropathologic features present in the hippocampus and the cerebellar vermis. Results Histologic and immunologic staining revealed abnormalities in both the hippocampus and cerebellar vermis. Focal thickening of hippocampal CA1 and irregularities in the appearance of the dentate gyrus were identified. All lobules of the cerebellar vermis and the lateral cortex of the posterior lobe of the cerebellum had decreased numbers of Purkinje cells, which were occasionally misplaced, and often lacked proper orientation. There were mild, albeit excessive, undulations of the internal granular cell layer, with patchy foliar white matter axonal and astrocytic abnormalities. Quantitative analysis documented panfoliar atrophy of both the anterior and posterior lobes of the vermis, with preferential atrophy of the posterior lobule (VI to VII compared with age-matched normal controls. Conclusions Significant morphologic changes in the hippocampus and cerebellum in three adult men with FXS were identified. This pattern of pathologic features supports the idea that primary defects in neuronal migration, neurogenesis and aging may underlie the neuropathology reported in FXS.

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

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    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.

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

    Science.gov (United States)

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Ichihara, Gaku

    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 8h/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.