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Scientific Reports Oct 2023The hippocampal formation is one of the best studied brain regions for spatial and mnemonic representations. These representations have been reported to differ in their...
The hippocampal formation is one of the best studied brain regions for spatial and mnemonic representations. These representations have been reported to differ in their properties for individual hippocampal subregions. One approach that allows the detection of neuronal representations is immediate early gene imaging, which relies on the visualization of genomic responses of activated neuronal populations, so called engrams. This method permits the within-animal comparison of neuronal representations across different subregions. In this work, we have used compartmental analysis of temporal activity by fluorescence in-situ hybridisation (catFISH) of the immediate early gene zif268/erg1 to compare neuronal representations between subdivisions of the dentate gyrus and CA3 upon exploration of different contexts. Our findings give an account of subregion-specific ensemble sizes. We confirm previous results regarding disambiguation abilities in dentate gyrus and CA3 but in addition report novel findings: Although ensemble sizes in the lower blade of the dentate gyrus are significantly smaller than in the upper blade both blades are responsive to environmental change. Beyond this, we show significant differences in the representation of familiar and novel environments along the longitudinal axis of dorsal CA3 and most interestingly between CA3 regions of both hemispheres.
Topics: Animals; Dentate Gyrus; Hippocampus; Neurons; Memory; Brain
PubMed: 37891194
DOI: 10.1038/s41598-023-45304-y -
Biological Psychiatry Sep 2020Parvalbumin (PV)-expressing interneurons are important for cognitive and emotional behaviors. These neurons express high levels of p11, a protein associated with...
BACKGROUND
Parvalbumin (PV)-expressing interneurons are important for cognitive and emotional behaviors. These neurons express high levels of p11, a protein associated with depression and action of antidepressants.
METHODS
We characterized the behavioral response to subthreshold stress in mice with conditional deletion of p11 in PV cells. Using chemogenetics, viral-mediated gene delivery, and a specific ion channel agonist, we studied the role of dentate gyrus PV cells in regulating anxiety-like behavior and resilience to stress. We used electrophysiology, imaging, and biochemical studies in mice and cells to elucidate the function and mechanism of p11 in dentate gyrus PV cells.
RESULTS
p11 regulates the subcellular localization and cellular level of the potassium channel Kv3.1 in cells. Deletion of p11 from PV cells resulted in reduced hippocampal level of Kv3.1, attenuated capacity of high-frequency firing in dentate gyrus PV cells, and altered short-term plasticity at synapses on granule cells, as well as anxiety-like behavior and a pattern separation deficit. Chemogenetic inhibition or deletion of p11 in these cells induced vulnerability to depressive behavior, whereas upregulation of Kv3.1 in dentate gyrus PV cells or acute activation of Kv3.1 using a specific agonist induced resilience to depression.
CONCLUSIONS
The activity of dentate gyrus PV cells plays a major role in the behavioral response to novelty and stress. Activation of the Kv3.1 channel in dentate gyrus PV cells may represent a target for the development of cell-type specific, fast-acting antidepressants.
Topics: Animals; Dentate Gyrus; Depression; Interneurons; Mice; Neurons; Parvalbumins
PubMed: 32331822
DOI: 10.1016/j.biopsych.2020.02.1179 -
Hippocampus Apr 2022Information processing in cortical circuits, including the hippocampus, relies on the dynamic control of neuronal activity by GABAergic interneurons (INs). INs form a...
Information processing in cortical circuits, including the hippocampus, relies on the dynamic control of neuronal activity by GABAergic interneurons (INs). INs form a heterogenous population with defined types displaying distinct morphological, molecular, and physiological characteristics. In the major input region of the hippocampus, the dentate gyrus (DG), a number of IN types have been described which provide synaptic inhibition to distinct compartments of excitatory principal cells (PrCs) and other INs. In this study, we perform an unbiased classification of GABAergic INs in the DG by combining in vitro whole-cell patch-clamp recordings, intracellular labeling, morphological analysis, and unsupervised cluster analysis to better define IN type diversity in this region. This analysis reveals that DG INs divide into at least 13 distinct morpho-physiological types which reflect the complexity of the local IN network and serve as a basis for further network analyses.
Topics: Animals; Dentate Gyrus; Hippocampus; Interneurons; Neurons; Patch-Clamp Techniques; Rats
PubMed: 35171512
DOI: 10.1002/hipo.23408 -
Hippocampus Nov 2021The dentate gyrus not only gates the flow of information into the hippocampus, it also integrates and processes this information. Mossy cells (MCs) are a major type of...
The dentate gyrus not only gates the flow of information into the hippocampus, it also integrates and processes this information. Mossy cells (MCs) are a major type of excitatory neuron strategically located in the hilus of the dentate gyrus where they can contribute to this processing through networks of synapses with inhibitory neurons and dentate granule cells. Some prior work has suggested that MCs can form excitatory synapses with other MCs, but the role of these synapses in the network activity of the dentate gyrus has received little attention. Here, we investigated synaptic inputs to MCs in mouse hippocampal slices using a genetically encoded hybrid voltage sensor (hVOS) targeted to MCs by Cre-lox technology. This enabled optical recording of voltage changes from multiple MCs simultaneously. Stimulating granule cells and CA3 pyramidal cells activated well-established inputs to MCs and elicited synaptic responses as expected. However, the weak blockade of MC responses to granule cell layer stimulation by DCG-IV raised the possibility of another source of excitation. To evaluate synapses between MCs as this source, single MCs were stimulated focally. Stimulation of one MC above its action potential threshold evoked depolarizing responses in neighboring MCs that depended on glutamate receptors. Short latency responses of MCs to other MCs did not depend on release from granule cell axons. However, granule cells did contribute to the longer latency responses of MCs to stimulation of other MCs. Thus, MCs transmit their activity to other MCs both through direct synaptic coupling and through polysynaptic coupling with dentate granule cells. MC-MC synapses can redistribute information entering the dentate gyrus and thus shape and modulate the electrical activity underlying hippocampal functions such as navigation and memory, as well as excessive excitation during seizures.
Topics: Animals; Dentate Gyrus; Hippocampus; Mice; Mossy Fibers, Hippocampal; Rats; Rats, Sprague-Dawley; Synapses
PubMed: 34478219
DOI: 10.1002/hipo.23386 -
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 -
Neurobiology of Learning and Memory Feb 2017Priming phenomenon, in which an earlier exposure to a stimulus or condition alters synaptic plasticity in response to a subsequent stimulus or condition, known as a... (Review)
Review
Priming phenomenon, in which an earlier exposure to a stimulus or condition alters synaptic plasticity in response to a subsequent stimulus or condition, known as a challenge, is an example of metaplasticity. In this review, we make the case that the locus coeruleus noradrenergic system-medial perforant path-dentate gyrus pathway is a neural ensemble amenable to studying priming-challenge effects on synaptic plasticity. Accumulating evidence points to a tyrosine hydroxylase-dependent priming effect achieved by pharmacological (nicotine and antipsychotics) or physiological (septal theta driving) manipulations of the locus coeruleus noradrenergic system that can facilitate noradrenaline-induced synaptic plasticity in the dentate gyrus of the hippocampus. The evidence suggests the hypothesis that behavioural experiences inducing tyrosine hydroxylase expression in the locus coeruleus may be sufficient to prime this form of metaplasticity. We propose exploring this phenomenon of priming and challenge physiologically, to determine whether behavioural experiences are sufficient to prime the locus coeruleus, enabling subsequent pharmacological or behavioural challenge conditions that increase locus coeruleus firing to release sufficient noradrenaline to induce long-lasting potentiation in the dentate gyrus. Such an approach may contribute to unravelling mechanisms underlying this form of metaplasticity and its importance in stress-related mnemonic processes.
Topics: Adrenergic Neurons; Animals; Dentate Gyrus; Locus Coeruleus; Neuronal Plasticity; Perforant Pathway; Tyrosine 3-Monooxygenase
PubMed: 27400867
DOI: 10.1016/j.nlm.2016.07.003 -
The Journal of Neuroscience : the... Apr 2022Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial...
Hilar mossy cells regulate network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial mossy cell loss accompanies hippocampal circuit changes in epilepsy. We examined the contribution of surviving mossy cells to network activity in the reorganized dentate gyrus after pilocarpine-induced status epilepticus (SE). To examine functional circuit changes, we optogenetically stimulated mossy cells in acute hippocampal slices from male mice. In control mice, activation of mossy cells produced monosynaptic excitatory and di-synaptic GABAergic currents in DGCs. In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition/excitation ratio. Surprisingly, mossy cell-driven excitation of parvalbumin-positive (PV+) basket cells, primary mediators of feed-forward inhibition, was maintained. Our results suggest that mossy cell outputs reorganize following seizures, increasing their net inhibitory effect in the hippocampus. Hilar mossy cell loss in epilepsy is associated with hippocampal hyperexcitability, potentially as a result of disrupted dentate microcircuit function. We used transgenic mice, translational mouse modeling, viral vectors, and optogenetics to selectively examine functional changes to mossy cell outputs following status epilepticus (SE). Interestingly, the outputs of surviving mossy cells exhibited adaptive plasticity onto target parvalbumin-positive (PV+) interneurons, resulting in a relative increase in their inhibitory control of dentate granule cells (DGCs). Our findings suggest that residual mossy cell outputs can reorganize in a homeostatic manner, which may provide clues for therapeutic targeting of this microcircuit.
Topics: Adaptation, Physiological; Animals; Dentate Gyrus; Male; Mice; Mossy Fibers, Hippocampal; Parvalbumins; Pilocarpine; Status Epilepticus
PubMed: 35181595
DOI: 10.1523/JNEUROSCI.1008-21.2022 -
ELife Jan 2021During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by...
During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.
Topics: Animals; Astrocytes; Dentate Gyrus; Female; Gene Deletion; Mice; Neurogenesis; Neuroglia
PubMed: 33393905
DOI: 10.7554/eLife.63904