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Nature Communications Dec 2019Fast-spiking parvalbumin-expressing interneurons (PVIs) and granule cells (GCs) of the dentate gyrus receive layer-specific dendritic inhibition. Its impact on PVI and...
Fast-spiking parvalbumin-expressing interneurons (PVIs) and granule cells (GCs) of the dentate gyrus receive layer-specific dendritic inhibition. Its impact on PVI and GC excitability is, however, unknown. By applying whole-cell recordings, GABA uncaging and single-cell-modeling, we show that proximal dendritic inhibition in PVIs is less efficient in lowering perforant path-mediated subthreshold depolarization than distal inhibition but both are highly efficient in silencing PVIs. These inhibitory effects can be explained by proximal shunting and distal strong hyperpolarizing inhibition. In contrast, GC proximal but not distal inhibition is the primary regulator of their excitability and recruitment. In GCs inhibition is hyperpolarizing along the entire somato-dendritic axis with similar strength. Thus, dendritic inhibition differentially controls input-output transformations in PVIs and GCs. Dendritic inhibition in PVIs is suited to balance PVI discharges in dependence on global network activity thereby providing strong and tuned perisomatic inhibition that contributes to the sparse representation of information in GC assemblies.
Topics: Action Potentials; Animals; Dendrites; Dentate Gyrus; Excitatory Postsynaptic Potentials; Female; Interneurons; Male; Nerve Net; Neural Inhibition; Neurons; Parvalbumins; Patch-Clamp Techniques; Rats, Wistar
PubMed: 31804491
DOI: 10.1038/s41467-019-13533-3 -
Surgical and Radiologic Anatomy : SRA Feb 2020Recent scientific papers indicate the clinical significance of the dentate gyrus. However, a detailed knowledge of the anatomical variations of this structure in normal...
Recent scientific papers indicate the clinical significance of the dentate gyrus. However, a detailed knowledge of the anatomical variations of this structure in normal adult brain is still lacking. An understanding of the variable morphology of the dentate gyrus may be important for diagnostic neuroimaging. Thus, the purpose of this macroscopic cadaveric study was to describe the anatomical variations of the dentate gyrus. Forty formalin-fixed human cerebral hemispheres, obtained from bodies of donors without the history of neuropathological diseases, were included in the study. The dentate gyrus was classified as well-developed, when it protruded completely from under the fimbria of the hippocampus. The gyrus was classified as underdeveloped, when it was covered by the fimbria of the hippocampus (but clearly visible at the coronal section of the hippocampal formation), while the hypoplastic gyrus was not visible macroscopically under the fimbria of the hippocampus. The well-developed type was observed in 27 cases (67.5%). The thickness of well-developed type of the dentate gyrus, measured between the fimbriodentate sulcus and hippocampal sulcus, varied from 2.74 to 5.21 mm (mean = 3.67 mm, median = 5.54 mm, SD 0.65 mm). In the next nine cases (22.5%), the dentate gyrus was underdeveloped. The thickness of underdeveloped type of the dentate gyrus varied from 1.75 to 2.37 mm (mean = 2.02 mm, median = 2.16 mm, SD 0.33 mm). In the remaining four cases (10%), the dentate gyrus was hypoplastic and could not be distinguished macroscopically. In all injected hemispheres, arterial supply of the dentate gyrus was provided by the branches of the posterior cerebral artery. Awareness of normal variations of the dentate gyrus may allow for better correlation of anatomical knowledge with radiological data and for use this knowledge to describe abnormal conditions.
Topics: Adult; Anatomic Variation; Cadaver; Dentate Gyrus; Humans
PubMed: 31372742
DOI: 10.1007/s00276-019-02298-5 -
Molecular Brain Nov 2022The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have...
The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have a long-lasting effect on cognitive function. Using an enriched environment (EE) paradigm, we have recently demonstrated that enhancing social, physical, and sensory activity during the pre-weaning time in mice led to an increase of inhibitory and excitatory synapses in the dentate gyrus (DG) of the hippocampus. The structural plasticity induced by experience may affect information processing in the circuit. The DG performs pattern separation, a computation that enables the encoding of very similar and overlapping inputs into dissimilar outputs. In the presented study, we have tested the hypothesis that an EE in juvenile mice will affect DG's functions that are relevant for pattern separation: the decorrelation of the inputs from the entorhinal cortex (EC) and the recruitment of the principal excitatory granule cell (GC) during behavior. First, using a novel slice electrophysiology protocol, we found that the transformation of the incoming signal from the EC afferents by individual GC is moderately affected by EE. We further show that EE does not affect behaviorally induced recruitment of principal excitatory GC. Lastly, using the novel object recognition task, a hippocampus-dependent memory test, we show that the ontogeny of this discrimination task was similar among the EE mice and the controls. Taken together, our work demonstrates that pre-weaning enrichment moderately affects DG function.
Topics: Animals; Mice; Dentate Gyrus; Hippocampus; Entorhinal Cortex; Neurons; Synapses
PubMed: 36411441
DOI: 10.1186/s13041-022-00980-1 -
ELife Feb 2022Memories encoded in the dentate gyrus (DG) ‒ CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1...
Memories encoded in the dentate gyrus (DG) ‒ CA3 circuit of the hippocampus are routed from CA1 to anterior cingulate cortex (ACC) for consolidation. Although CA1 parvalbumin inhibitory neurons (PV INs) orchestrate hippocampal-cortical communication, we know less about CA3 PV INs or DG ‒ CA3 principal neuron ‒ IN circuit mechanisms that contribute to evolution of hippocampal-cortical ensembles during memory consolidation. Using viral genetics to selectively mimic and boost an endogenous learning-dependent circuit mechanism, DG cell recruitment of CA3 PV INs and feed-forward inhibition (FFI) in CA3, in combination with longitudinal calcium imaging, we demonstrate that FFI facilitates formation and maintenance of context-associated neuronal ensembles in CA1. Increasing FFI in DG ‒ CA3 promoted context specificity of neuronal ensembles in ACC over time and enhanced long-term contextual fear memory. LFP recordings in mice with increased FFI in DG ‒ CA3 identified enhanced CA1 sharp-wave ripple ‒ ACC spindle coupling as a potential network mechanism facilitating memory consolidation. Our findings illuminate how FFI in DG ‒ CA3 dictates evolution of ensemble properties in CA1 and ACC during memory consolidation and suggest a teacher-like function for hippocampal CA1 in stabilization and re-organization of cortical representations.
Topics: Animals; Dentate Gyrus; Hippocampus; Memory Consolidation; Memory, Long-Term; Mice; Parvalbumins
PubMed: 35191834
DOI: 10.7554/eLife.70586 -
Journal of Neurophysiology Feb 2004Parallel recordings of hippocampal principal cells and interneurons were obtained as rats foraged in familiar and adjacent, novel environments. Firing rates of each cell... (Comparative Study)
Comparative Study
Parallel recordings of hippocampal principal cells and interneurons were obtained as rats foraged in familiar and adjacent, novel environments. Firing rates of each cell type were assessed as a function of spatial location. Many CA1 interneurons exhibited large decreases in activity in the novel compared with the familiar environment. Dentate gyrus interneurons, however, were much more likely to exhibit large increases in firing in the novel environment. Neither effect was correlated with basic interneuron discharge properties such as degree of theta modulation, baseline firing rate or degree of spatially modulated discharge. Both CA1 and dentate gyrus interneuron rate changes extended into regions of the familiar environment bordering the novel environment. Principal cells in CA1 and dentate gyrus exhibited similar patterns of place specific activity each being indicative of incorporation of novel spatial information into the spatial representation of the familiar environment. The data indicate that inhibitory networks in the CA1 and dentate gyrus areas are modulated in a divergent fashion during the acquisition of novel spatial information and that interneuron activities can be used to detect those regions of an environment subject to redistribution of principal cell spatial activity patterns.
Topics: Action Potentials; Animals; Dentate Gyrus; Environment; Exploratory Behavior; Interneurons; Rats; Rats, Inbred F344
PubMed: 14523073
DOI: 10.1152/jn.00614.2003 -
PLoS Computational Biology Feb 2024Pattern separation is a valuable computational function performed by neuronal circuits, such as the dentate gyrus, where dissimilarity between inputs is increased,...
Pattern separation is a valuable computational function performed by neuronal circuits, such as the dentate gyrus, where dissimilarity between inputs is increased, reducing noise and increasing the storage capacity of downstream networks. Pattern separation is studied from both in vivo experimental and computational perspectives and, a number of different measures (such as orthogonalisation, decorrelation, or spike train distance) have been applied to quantify the process of pattern separation. However, these are known to give conclusions that can differ qualitatively depending on the choice of measure and the parameters used to calculate it. We here demonstrate that arbitrarily increasing sparsity, a noticeable feature of dentate granule cell firing and one that is believed to be key to pattern separation, typically leads to improved classical measures for pattern separation even, inappropriately, up to the point where almost all information about the inputs is lost. Standard measures therefore both cannot differentiate between pattern separation and pattern destruction, and give results that may depend on arbitrary parameter choices. We propose that techniques from information theory, in particular mutual information, transfer entropy, and redundancy, should be applied to penalise the potential for lost information (often due to increased sparsity) that is neglected by existing measures. We compare five commonly-used measures of pattern separation with three novel techniques based on information theory, showing that the latter can be applied in a principled way and provide a robust and reliable measure for comparing the pattern separation performance of different neurons and networks. We demonstrate our new measures on detailed compartmental models of individual dentate granule cells and a dentate microcircuit, and show how structural changes associated with epilepsy affect pattern separation performance. We also demonstrate how our measures of pattern separation can predict pattern completion accuracy. Overall, our measures solve a widely acknowledged problem in assessing the pattern separation of neural circuits such as the dentate gyrus, as well as the cerebellum and mushroom body. Finally we provide a publicly available toolbox allowing for easy analysis of pattern separation in spike train ensembles.
Topics: Dentate Gyrus; Information Theory; Neurons; Brain; Models, Neurological
PubMed: 38377108
DOI: 10.1371/journal.pcbi.1010706 -
ASN Neuro 2015Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at...
Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.
Topics: Anesthetics, Inhalation; Animals; Animals, Newborn; Bromodeoxyuridine; Cell Count; Cell Proliferation; Cell Survival; Dentate Gyrus; Discrimination Learning; Fear; Immunohistochemistry; Male; Maze Learning; Methyl Ethers; Neurogenesis; Neurons; Patch-Clamp Techniques; Random Allocation; Rats, Sprague-Dawley; Sevoflurane; Tissue Culture Techniques
PubMed: 25873307
DOI: 10.1177/1759091415575845 -
Neurobiology of Learning and Memory May 2008We have previously described the transcriptional changes that occur in the hippocampal CA1 field of aged rats following a Morris Water Maze (MWM) training paradigm. In...
We have previously described the transcriptional changes that occur in the hippocampal CA1 field of aged rats following a Morris Water Maze (MWM) training paradigm. In this report we proceed with the analysis of the dentate region from the same animals. Animals were first identified as age learning-impaired or age-superior learners when compared to young rats based on their performance in the MWM. Messenger RNA was isolated from the dentate gyrus of each animal to interrogate Affymetrix RAE 230A rat genome microarrays. Microarray profiling identified 1129 genes that were differentially expressed between aged and young rats as a result of aging, and independent of their behavioral training (p<0.005). We applied Ingenuity Pathway Analysis (IPA) algorithms to identify the significant biological processes underlying age-related changes in the dentate gyrus. The most significant functions, as calculated by IPA, included cell movement, cell growth and proliferation, nervous system development and function, cellular assembly and organization, cell morphology and cell death. These significant processes are consistent with age-related changes in neurogenesis, and the neurogenic markers were generally found to be downregulated in senescent animals. In addition, statistical analysis of the different experimental groups of aged animals recognized 85 genes (p<0.005) that were different in the dentate gyrus of aged rats that had learned the MWM when compared to learning impaired and a number of controls for stress, exercise and non-spatial learning. The list of learning-related genes expressed in the dentate adds to the set of genes we previously described in the CA1 region. This long list of genes constitutes a starting tool to elucidating the molecular pathways involved in learning and memory formation.
Topics: Aging; Animals; Cell Death; Cell Division; Cell Movement; Dentate Gyrus; Gene Expression Profiling; Genomics; Male; Maze Learning; Memory; Neurons; Oligonucleotide Array Sequence Analysis; Rats; Rats, Inbred F344
PubMed: 18234529
DOI: 10.1016/j.nlm.2007.11.006 -
Epilepsia Jun 2008Status epilepticus (SE) not only results in an increased number of newly generated neurons in the dentate gyrus but also leads to structural alterations of many of these... (Review)
Review
Status epilepticus (SE) not only results in an increased number of newly generated neurons in the dentate gyrus but also leads to structural alterations of many of these newborn granule cells. One of the structural changes involving newly generated dentate granule cells is the formation of hilar basal dendrites that persist on mature granule cells and integrate into synaptic circuitry. SE also causes other newborn granule cells to migrate ectopically into the hilus, and these cells also integrate into synaptic circuitry. This article will describe these structural alterations of granule cells found in the dentate gyrus after SE and will also discuss the time course of these events and possible underlying causes.
Topics: Adult Stem Cells; Animals; Dentate Gyrus; Humans; Neurons; Status Epilepticus
PubMed: 18522596
DOI: 10.1111/j.1528-1167.2008.01633.x -
Learning & Memory (Cold Spring Harbor,... Nov 2013In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the... (Review)
Review
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 after the perinatal period suggests that unique aspects of the structure and function of DG and olfactory bulb circuits allow them to benefit from the adult generation of neurons. In this review, we consider the distinctive features of the DG that may account for it being able to profit from this singular form of neural plasticity. Approaches to the problem of neurogenesis are grouped as "bottom-up," where the phenotype of adult-born granule cells is contrasted to that of mature developmentally born granule cells, and "top-down," where the impact of altering the amount of neurogenesis on behavior is examined. We end by considering the primary implications of these two approaches and future directions.
Topics: Animals; Dentate Gyrus; Neurogenesis; Neurons
PubMed: 24255101
DOI: 10.1101/lm.026542.112