pinecone/core-2020-05-10-deduplication huggingface dataset:
Lateral entorhinal cortex is critical for novel object-context recognition

Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c-fos expression during an object-context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c-fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object-context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object-context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus. © 2013 Wiley Periodicals, Inc.Publisher PDFPeer reviewe
Sex-dependent regulation of hippocampal neurogenesis under basal and chronic stress conditions in rats.

Sex differences in basal as well as in stress-induced hippocampal neurogenesis processes have been reported in the literature. However, studies directly comparing sex differences on multiple neurogenesis processes under such conditions are lacking to date. Therefore, the aim of the present study was to directly compare cell proliferation and survival, neuronal and astroglial differentiation as well as stem cells quiescence in male and female Wistar rats under both basal and chronic stress conditions (12 days of 2 h restraint stress (RS)). In addition, corticosterone (CORT) levels and spatial working memory were assessed. Under baseline conditions, only the number of immature neurons within the hippocampal dentate gyrus was higher in males compared with females. In contrast, chronic stress resulted in a number of sex-specific alterations. Thus, stress exposure reduced cell proliferation in males with a concurrent increase in stem cell quiescence, while it did not alter either parameter in females but decreased cell survival. Analysis of astroglial and neuronal differentiation patterns revealed that chronic stress specifically diminished the number of mature neurons in females, with no effect in males. Despite the observed sex differences in adult hippocampal neurogenesis, spatial working memory was not altered by stress exposure in either sex. While basal CORT levels were higher, chronic stress exposure did not affect this parameter in either sex across the initial stress period. This study presents the first direct and detailed evaluation of sex-dependent and chronic stress-induced changes in adult hippocampal neurogenesis not only showing changes in cell proliferation and survival, but moreover immature neuron production, differentiation patterns, stem cell quiescence and therefore contributes to a better understanding of sex differences in neurogenesis processes
Different Input and Output Properties Characterize Parvalbumin-Positive Basket and Axo-Axonic Cells in the Hippocampal CA3 Subﬁeld

In the hippocampus, parvalbumin-expressing basket (BC) and axo-axonic cells (AAC) show different discharge patterns during distinct network states, but the cellular mechanisms underlying these differences are not well understood. Using whole-cell patch-clamp techniques, we investigated the single-cell properties and excitatory synaptic features of anatomically identified BCs and AACs in the CA3 region of mouse hippocampal slices. The results showed that BCs had lower threshold for action potential (AP) generation and lower input resistance, narrower AP and afterhyperpolarization than AACs. In addition, BCs fired with higher frequencies and with more modest accommodation compared to AACs. The kinetic properties of excitatory postsynaptic currents (EPSC), the rectification of AMPA receptor-mediated currents, the fraction of the NMDA receptor-mediated component in EPSCs, and the EPSC magnitude necessary to evoke an AP were similar in both cell types. However, smaller excitatory postsynaptic potential and lower intensity fiber stimulation in stratum oriens was necessary to drive firing in BCs. Moreover, the rate of spontaneous EPSCs in BCs was higher than in AACs. Neurolucida analysis revealed that the dendrites of BCs in strata radiatum and oriens were longer and more extensively ramified. Since the density of the excitatory synapses was estimated to be comparable in both cell types, we conclude that the more elaborated dendritic arbor of BCs ensures that they receive a larger number of proximal excitatory inputs. Thus, CA3 pyramidal cells more profoundly innervate BCs than AACs, which could explain, at least in part, their distinct spiking behavior under different hippocampal network activities
Representations of recent and remote autobiographical memories in hippocampal subfields

The hippocampus has long been implicated in supporting autobiographical memories, but little is known about how they are instantiated in hippocampal subfields. Using high-resolution functional magnetic resonance imaging (fMRI) combined with multivoxel pattern analysis we found that it was possible to detect representations of specific autobiographical memories in individual hippocampal subfields. Moreover, while subfields in the anterior hippocampus contained information about both recent (2 weeks old) and remote (10 years old) autobiographical memories, posterior CA3 and DG only contained information about the remote memories. Thus, the hippocampal subfields are differentially involved in the representation of recent and remote autobiographical memories during vivid recall
Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory

This work was supported by BBSRC [Grant number BB/I019367/1]The lateral entorhinal cortex (LEC) provides one of the two major input pathways to the hippocampus and has been suggested to process the nonspatial contextual details of episodic memory. Combined with spatial information from the medial entorhinal cortex it is hypothesised that this contextual information is used to form an integrated spatially selective, context-specific response in the hippocampus that underlies episodic memory. Recently, we reported that the LEC is required for recognition of objects that have been experienced in a specific context (Wilson et al. (2013) Hippocampus 23:352-366). Here, we sought to extend this work to assess the role of the LEC in recognition of all associative combinations of objects, places and contexts within an episode. Unlike controls, rats with excitotoxic lesions of the LEC showed no evidence of recognizing familiar combinations of object in place, place in context, or object in place and context. However, LEC lesioned rats showed normal recognition of objects and places independently from each other (nonassociative recognition). Together with our previous findings, these data suggest that the LEC is critical for associative recognition memory and may bind together information relating to objects, places, and contexts needed for episodic memory formation.Publisher PDFPeer reviewe
A model for the differentiation between grid and conjunctive units in medial entorhinal cortex

The multiple layers of medial entorhinal cortex (mEC) contain cells that differ in selectivity, connectivity, and cellular properties. Grid cells in layer II and in the deeper layers express triangular grid patterns in the environment. The firing rate of the conjunctive cells found in layer III and below, on the other hand, show grid-by-head direction tuning. In this study, we model the differentiation between grid and conjunctive cells in a network with self-organized connections. Arranged into distinct layers, the model grid units and conjunctive units develop, with a similar time course, grid fields resulting from firing rate adaptation and competitive learning. Grid alignment in both layers is delayed with respect to the formation of triangular grids. A common grid orientation among conjunctive units is produced, in the model, by head-direction modulated collateral interactions, while the grids of grid units inherit the same orientation through connections from conjunctive units. Grid units as well as conjunctive units share a similar spacing but show a random distribution of spatial phases. Grid units however carry more spatial information than conjunctive units, thus providing better inputs for the hippocampus to form spatial memorie
Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer's disease

Genetic screening in Alzheimer's disease (AD) has identified only a handful of genes that are mutated in the disorder. Thus, for a very large proportion of patients, the biology of their disease is poorly understood. Epigenetic alterations may provide an explanation in these cases. Using DNA methylation profiles of human hippocampus from controls and patients, we have identified the presence of promoter hypermethylation of the dual-specificity phosphatase 22 (DUSP22) gene in AD. DUSP22 is a likely candidate gene for involvement in the pathogenesis of the disorder since, as we demonstrate here, it inhibits PKA activity and thereby determines TAU phosphorylation status and CREB signaling
Brain-derived neurotrophic factor interacts with adult-born immature cells in the dentate gyrus during consolidation of overlapping memories

Successful memory involves not only remembering information over time but also keeping memories distinct and less confusable. The computational process for making representations of similar input patterns more distinct from each other has been referred to as “pattern separation.” Although adult-born immature neurons have been implicated in this memory feature, the precise role of these neurons and associated molecules in the processing of overlapping memories is unknown. Recently, we found that brain-derived neurotrophic factor (BDNF) in the dentate gyrus is required for the encoding/consolidation of overlapping memories. In this study, we provide evidence that consolidation of these “pattern-separated” memories requires the action of BDNF on immature neurons specifically.Fil: Bekinschtein, Pedro Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. University of Cambridge; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kent, Brianne A.. University of Cambridge; Reino UnidoFil: Oomen, Charlotte. University of Cambridge; Reino UnidoFil: Gregory D. Clemenson. Salk Institute For Biological Studies; Estados UnidosFil: Fred H. Gage. Salk Institute For Biological Studies; Estados UnidosFil: Lisa M. Saksida. University of Cambridge; Reino UnidoFil: Timothy J. Bussey. University of Cambridge; Reino Unid
Brain-Derived Neurotrophic Factor Interacts with Adult-Born Immature Cells in the Dentate Gyrus During Consolidation of Overlapping Memories

Successful memory involves not only remembering information over time but also keeping memories distinct and less confusable. The computational process for making representations of similar input patterns more distinct from each other has been referred to as “pattern separation.” Although adult-born immature neurons have been implicated in this memory feature, the precise role of these neurons and associated molecules in the processing of overlapping memories is unknown. Recently, we found that brain-derived neurotrophic factor (BDNF) in the dentate gyrus is required for the encoding/consolidation of overlapping memories. In this study, we provide evidence that consolidation of these “pattern-separated” memories requires the action of BDNF on immature neurons specifically. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.The Biotechnology and Biological Sciences Research Council . Grant Number: BB/G019002/1
The Innovative Medicine Initiative Joint Undertaking . Grant Number: 115008
The European Union's Seventh Framework Programme . Grant Number: FP7/2007-2013
The James S. McDonnell Foundation, Mather's Foundation, NIMH, Ellison Foundation, NINDS, NIMH, NIA, JPB FoundationThis is the final published version, which can also be viewed online at: http://onlinelibrary.wiley.com/doi/10.1002/hipo.22304/ful
Anatomically heterogeneous populations of CB cannabinoid receptor-expressing interneurons in the CA3 region of the hippocampus show homogeneous input-output characteristics

A subpopulation of GABAergic cells in cortical structures expresses CB1 cannabinoid receptors (CB1 ) on their axon terminals. To understand the function  of these interneurons in information processing, it is necessary to uncover how they are embedded into neuronal circuits. Therefore, the proportion of GABAergic  terminals expressing CB1 and the morphological and electrophysiological properties of CB1 -immunoreactive interneurons should be revealed. We investigated the ratio and the origin of CB1 -expressing inhibitory boutons in the CA3 region of the hippocampus. Using immunocytochemical techniques, we estimated that approximately 40% of GABAergic axon terminals in different layers  of CA3 also expressed CB1 . To identify the inhibitory cell types expressing CB1  in this region, we recorded and intracellularly labeled interneurons in hippocampal slices. CB1 -expressing interneurons showed distinct axonal arborization, and were classified as basket cells, mossy-fiber-associated cells,  dendritic-layer-innervating cells or perforant-path-associated cells. In each morphological category, a substantial variability in axonal projection was observed. In contrast to the diverse morphology, the active and passive membrane  properties were found to be rather similar. Using paired recordings, we found that pyramidal cells displayed large and fast unitary postsynaptic currents in response to activating basket and mossy-fiber-associated cells, while they showed slower and smaller synaptic events in pairs originating from interneurons that innervate the dendritic layer, which may be due to dendritic filtering. In addition, CB1 activation significantly reduced the amplitude of the postsynaptic  currents in each cell pair tested. Our data suggest that CB1 -expressing interneurons with different axonal projections have comparable physiological characteristics, contributing to a similar proportion of GABAergic inputs along the somato-dendritic axis of CA3 pyramidal cells. (c) 2014 Wiley Periodicals, Inc
The hippocampal CA3 region can generate two distinct types of sharp wave-ripple complexes, in vitro.

Hippocampal sharp wave-ripples (SPW-Rs) occur during slow wave sleep and behavioral immobility and are thought to play an important role in memory formation. We investigated the cellular and network properties of SPW-Rs with simultaneous laminar multielectrode and intracellular recordings in a rat hippocampal slice model, using physiological bathing medium. Spontaneous SPW-Rs were generated in the dentate gyrus (DG), CA3 and CA1 regions. These events were  characterized by a local field potential gradient (LFPg) transient, increased fast oscillatory activity and increased multiple unit activity (MUA). Two types of SPW-Rs were distinguished in the CA3 region based on their different LFPg and  current source density (CSD) pattern. Type 1 (T1) displayed negative LFPg transient in the pyramidal cell layer, and the associated CSD sink was confined to the proximal dendrites. Type 2 (T2) SPW-Rs were characterized by positive LFPg transient in the cell layer, and showed CSD sinks involving both the apical and basal dendrites. In both types, consistent with the somatic CSD source, only a small subset of CA3 pyramidal cells fired, most pyramidal cells were hyperpolarized, while most interneurons increased firing rate before the LFPg peak. Different neuronal populations, with different proportions of pyramidal cells and distinct subsets of interneurons were activated during T1 and T2 SPW-Rs. Activation of specific inhibitory cell subsets - with the possible leading role of perisomatic interneurons - seems to be crucial to synchronize distinct ensembles of CA3 pyramidal cells finally resulting in the expression of  different SPW-R activities. This suggests that the hippocampus can generate dynamic changes in its activity stemming from the same excitatory and inhibitory  circuits, and so, might provide the cellular and network basis for an input-specific and activity-dependent information transmission. (c) 2014 Wiley Periodicals, Inc
Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous Amyloid β peptide.

This is the accepted version of the article, which has been published in final form at DOI: 10.1002/hipo.22403Accumulation of Aβ peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ-overexpressing transgenic mice indicates that elevated brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study we examined what changes in IE are produced in hippocampal CA1 pyramidal cells following 2-5 hours treatment with an oligomeric preparation of synthetic human Aβ1-42 peptide. Whole cell current clamp recordings were compared between Aβ-(500nM) and vehicle-(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub-threshold intrinsic properties including membrane potential, input resistance and hyperpolarization activated "sag". Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra-threshold stimuli. However, Aβ 500nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500nM depressed the after-hyperpolarization (AHP) that followed both a 1 single AP or 50Hz trains of between 5 and 25 APs. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models the IE changes are towards hyper-excitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. This article is protected by copyright. All rights reserved.MR
Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP-expressing retrovirus. Animals were exposed to a reference memory protocol for 10-14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM.Fil: Trinchero, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Koehl, Muriel. Inserm; FranciaFil: Bechakra, Malik. Inserm; Francia. Universite de Bordeaux; FranciaFil: Delage, Pauline. Inserm; Francia. Universite de Bordeaux; FranciaFil: Charrier, Vanessa. Inserm; Francia. Universite de Bordeaux; FranciaFil: Grosjean, Noelle. Inserm; Francia. Universite de Bordeaux; FranciaFil: Lavedeze, Elodie. Inserm; Francia. Universite de Bordeaux; FranciaFil: Schinder, Alejandro Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Abrous, D. Nora. Inserm; Francia. Universite de Bordeaux; Franci
Differentiation of forebrain and hippocampal dopamine 1-class receptors, D1R and D5R, in spatial learning and memory

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R-specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory