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The Journal of Comparative Neurology Feb 2016The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in... (Review)
Review
The dentate gyrus (DG), a part of the hippocampal formation, has important functions in learning, memory, and adult neurogenesis. Compared with homologous areas in sauropsids (birds and reptiles), the mammalian DG is larger and exhibits qualitatively different phenotypes: 1) folded (C- or V-shaped) granule neuron layer, concave toward the hilus and delimited by a hippocampal fissure; 2) nonperiventricular adult neurogenesis; and 3) prolonged ontogeny, involving extensive abventricular (basal) migration and proliferation of neural stem and progenitor cells (NSPCs). Although gaps remain, available data indicate that these DG traits are present in all orders of mammals, including monotremes and marsupials. The exception is Cetacea (whales, dolphins, and porpoises), in which DG size, convolution, and adult neurogenesis have undergone evolutionary regression. Parsimony suggests that increased growth and convolution of the DG arose in stem mammals concurrently with nonperiventricular adult hippocampal neurogenesis and basal migration of NSPCs during development. These traits could all result from an evolutionary change that enhanced radial migration of NSPCs out of the periventricular zones, possibly by epithelial-mesenchymal transition, to colonize and maintain nonperiventricular proliferative niches. In turn, increased NSPC migration and clonal expansion might be a consequence of growth in the cortical hem (medial patterning center), which produces morphogens such as Wnt3a, generates Cajal-Retzius neurons, and is regulated by Lhx2. Finally, correlations between DG convolution and neocortical gyrification (or capacity for gyrification) suggest that enhanced abventricular migration and proliferation of NSPCs played a transformative role in growth and folding of neocortex as well as archicortex.
Topics: Animals; Biological Evolution; Dentate Gyrus; Mammals; Neural Pathways; Neurogenesis; Neurons
PubMed: 26179319
DOI: 10.1002/cne.23851 -
Current Biology : CB Mar 2022The hippocampus is involved in the formation of memories that require associations among stimuli to construct representations of space and the items and events within...
The hippocampus is involved in the formation of memories that require associations among stimuli to construct representations of space and the items and events within that space. Neurons in the dentate gyrus (DG), an initial input region of the hippocampus, have robust spatial tuning, but it is unclear how nonspatial information may be integrated with spatial activity in this region. We recorded from the DG of 21 adult mice as they foraged for food in an environment that contained discrete objects. We found DG cells with multiple firing fields at a fixed distance and direction from objects (landmark vector cells) and cells that exhibited localized changes in spatial firing when objects in the environment were manipulated. By classifying recorded DG cells into putative dentate granule cells and mossy cells, we examined how the addition or displacement of objects affected the spatial firing of these DG cell types. Object-related activity was detected in a significant proportion of mossy cells. Although few granule cells with responses to object manipulations were recorded, likely because of the sparse nature of granule cell firing, there was generally no significant difference in the proportion of granule cells and mossy cells with object responses. When mice explored a second environment with the same objects, DG spatial maps completely reorganized, and a different subset of cells responded to object manipulations. Together, these data reveal the capacity of DG cells to detect small changes in the environment while preserving a stable spatial representation of the overall context.
Topics: Animals; Dentate Gyrus; Hippocampus; Mice; Neurons
PubMed: 35108522
DOI: 10.1016/j.cub.2022.01.023 -
The Journal of Neuroscience : the... Feb 2021Mossy cells (MCs) of the dentate gyrus (DG) are a major group of excitatory hilar neurons that are important for regulating activity of dentate granule cells. MCs are...
Mossy cells (MCs) of the dentate gyrus (DG) are a major group of excitatory hilar neurons that are important for regulating activity of dentate granule cells. MCs are particularly intriguing because of their extensive longitudinal connections within the DG. It has generally been assumed that MCs in the dorsal and ventral DG have similar patterns of termination in the inner one-third of the dentate molecular layer. Here, we demonstrate that axonal projections of MCs in these two regions are considerably different. MCs in dorsal and ventral regions were labeled selectively with Cre-dependent eYFP or mCherry, using two transgenic mouse lines (including both sexes) that express Cre-recombinase in MCs. At four to six weeks following unilateral labeling of MCs in the ventral DG, a dense band of fibers was present in the inner one-fourth of the molecular layer and extended bilaterally throughout the rostral-caudal extent of the DG, replicating the expected distribution of MC axons. In contrast, following labeling of MCs in the dorsal DG, the projections were more diffusely distributed. At the level of transfection, fibers were present in the inner molecular layer, but they progressively expanded into the middle molecular layer and, most ventrally, formed a distinct band in this region. Optical stimulation of these caudal fibers expressing ChR2 demonstrated robust EPSCs in ipsilateral granule cells and enhanced the effects of perforant path stimulation in the ventral DG. These findings suggest that MCs in the dorsal and ventral DG differ in the distribution of their axonal projections and possibly their function. Mossy cells (MCs), a major cell type in the hilus of the dentate gyrus (DG), are unique in providing extensive longitudinal and commissural projections throughout the DG. Although it has been assumed that all MCs have similar patterns of termination in the inner molecular layer of the DG, we discovered that the axonal projections of dorsal and ventral MCs differ. While ventral MC projections exhibit the classical pattern, with dense innervation in the inner molecular layer, dorsal MCs have a more diffuse distribution and expand into the middle molecular layer where they overlap and interact with innervation from the perforant path. These distinct locations and patterns of axonal projections suggest that dorsal and ventral MCs may have different functional roles.
Topics: Animals; Axons; Dentate Gyrus; Excitatory Postsynaptic Potentials; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mossy Fibers, Hippocampal; Optogenetics
PubMed: 33268544
DOI: 10.1523/JNEUROSCI.2455-20.2020 -
Neurobiology of Learning and Memory Mar 2016The dentate gyrus (DG) and area CA3 of the hippocampus are highly organized lamellar structures which have been implicated in specific cognitive functions such as... (Review)
Review
The dentate gyrus (DG) and area CA3 of the hippocampus are highly organized lamellar structures which have been implicated in specific cognitive functions such as pattern separation and pattern completion. Here we describe how the anatomical organization and physiology of the DG and CA3 are consistent with structures that perform pattern separation and completion. We then raise a new idea related to the complex circuitry of the DG and CA3 where CA3 pyramidal cell 'backprojections' play a potentially important role in the sparse firing of granule cells (GCs), considered important in pattern separation. We also propose that GC axons, the mossy fibers, already known for their highly specialized structure, have a dynamic function that imparts variance--'mossy fiber variance'--which is important to pattern separation and completion. Computational modeling is used to show that when a subset of GCs become 'dominant,' one consequence is loss of variance in the activity of mossy fiber axons and a reduction in pattern separation and completion in the model. Empirical data are then provided using an example of 'dominant' GCs--subsets of GCs that develop abnormally and have increased excitability. Notably, these abnormal GCs have been identified in animal models of disease where DG-dependent behaviors are impaired. Together these data provide insight into pattern separation and completion, and suggest that behavioral impairment could arise from dominance of a subset of GCs in the DG-CA3 network.
Topics: Action Potentials; Animals; Brain Diseases; CA3 Region, Hippocampal; Dentate Gyrus; Humans; Memory; Models, Neurological; Neural Networks, Computer; Neural Pathways; Neurons; Pattern Recognition, Physiological
PubMed: 26391451
DOI: 10.1016/j.nlm.2015.09.005 -
Cell and Tissue Research Sep 2018A quantitative computational theory of the operation of the hippocampus as an episodic memory system is described. The CA3 system operates as a single attractor or... (Review)
Review
A quantitative computational theory of the operation of the hippocampus as an episodic memory system is described. The CA3 system operates as a single attractor or autoassociation network (1) to enable rapid one-trial associations between any spatial location (place in rodents or spatial view in primates) and an object or reward and (2) to provide for completion of the whole memory during recall from any part. The theory is extended to associations between time and object or reward to implement temporal order memory, which is also important in episodic memory. The dentate gyrus performs pattern separation by competitive learning to create sparse representations producing, for example, neurons with place-like fields from entorhinal cortex grid cells. The dentate granule cells generate, by the very small number of mossy fibre connections to CA3, a randomizing pattern separation effect that is important during learning but not recall and that separates out the patterns represented by CA3 firing as being very different from each other. This is optimal for an unstructured episodic memory system in which each memory must be kept distinct from other memories. The direct perforant path input to CA3 is quantitatively appropriate for providing the cue for recall in CA3 but not for learning. The CA1 recodes information from CA3 to set up associatively learned backprojections to the neocortex to allow the subsequent retrieval of information to the neocortex, giving a quantitative account of the large number of hippocampo-neocortical and neocortical-neocortical backprojections. Tests of the theory including hippocampal subregion analyses and hippocampal NMDA receptor knockouts are described and support the theory.
Topics: Animals; Dentate Gyrus; Hippocampus; Humans; Memory, Episodic; Mental Recall; Models, Neurological; Neocortex; Neurons; Primates; Spatial Navigation
PubMed: 29218403
DOI: 10.1007/s00441-017-2744-3 -
Nature Reviews. Neuroscience Sep 2016Mossy cells comprise a large fraction of the cells in the hippocampal dentate gyrus, suggesting that their function in this region is important. They are vulnerable to... (Review)
Review
Mossy cells comprise a large fraction of the cells in the hippocampal dentate gyrus, suggesting that their function in this region is important. They are vulnerable to ischaemia, traumatic brain injury and seizures, and their loss could contribute to dentate gyrus dysfunction in such conditions. Mossy cell function has been unclear because these cells innervate both glutamatergic and GABAergic neurons within the dentate gyrus, contributing to a complex circuitry. It has also been difficult to directly and selectively manipulate mossy cells to study their function. In light of the new data generated using methods to preferentially eliminate or activate mossy cells in mice, it is timely to ask whether mossy cells have become any less enigmatic than they were in the past.
Topics: Animals; Axons; Bryophyta; Dentate Gyrus; Epilepsy; Hippocampus; Humans; Neurons
PubMed: 27466143
DOI: 10.1038/nrn.2016.87 -
Neuroscience Letters Aug 2021The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular... (Review)
Review
The subgranular zone of the dentate gyrus provides a local microenvironment (niche) for neural stem cells. In the adult brain, it has been established that the vascular compartment of such niches has a significant role in regulating adult hippocampal neurogenesis. More recently, evidence showed that neurovascular coupling, the relationship between blood flow and neuronal activity, also regulates hippocampal neurogenesis. Here, we review the most recent articles on addressing the intricate relationship between neurovasculature and adult hippocampal neurogenesis and a novel pathway where functional hyperemia enhances hippocampal neurogenesis. In the end, we have further reviewed recent research showing that impaired neurovascular coupling may cause declined neurogenesis and contribute to brain damage in neurodegenerative diseases.
Topics: Adult; Alzheimer Disease; Animals; Dentate Gyrus; Disease Models, Animal; Humans; Interneurons; Neovascularization, Physiologic; Neural Stem Cells; Neurogenesis; Nitric Oxide Synthase Type I; Parvalbumins; Vascular Endothelial Growth Factor A
PubMed: 34147540
DOI: 10.1016/j.neulet.2021.136071 -
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 -
Nature Communications Aug 2020New neurons are generated in adult mammals. Adult hippocampal neurogenesis is considered to play an important role in cognition and mental health. The number and... (Review)
Review
New neurons are generated in adult mammals. Adult hippocampal neurogenesis is considered to play an important role in cognition and mental health. The number and properties of newly born neurons are regulatable by a broad range of physiological and pathological conditions. To begin to understand the underlying cellular mechanisms and functional relevance of adult neurogenesis, many studies rely on quantification of adult-born neurons. However, lack of standardized methods to quantify new neurons is impeding research reproducibility across laboratories. Here, we review the importance of stereology, and propose why and how it should be applied to the study of adult neurogenesis.
Topics: Adult; Adult Stem Cells; Animals; Brain; Dentate Gyrus; Humans; Models, Neurological; Neural Stem Cells; Neurogenesis; Neuronal Plasticity
PubMed: 32848155
DOI: 10.1038/s41467-020-18046-y -
Cell Reports Apr 2023Hippocampal place cells exhibit spatially modulated firing, or place fields, which can remap to encode changes in the environment or other variables. Unique among...
Hippocampal place cells exhibit spatially modulated firing, or place fields, which can remap to encode changes in the environment or other variables. Unique among hippocampal subregions, the dentate gyrus (DG) has two excitatory populations of place cells, granule cells and mossy cells, which are among the least and most active spatially modulated cells in the hippocampus, respectively. Previous studies of remapping in the DG have drawn different conclusions about whether granule cells exhibit global remapping and contribute to the encoding of context specificity. By recording granule cells and mossy cells as mice foraged in different environments, we found that by most measures, both granule cells and mossy cells remapped robustly but through different mechanisms that are consistent with firing properties of each cell type. Our results resolve the ambiguity surrounding remapping in the DG and suggest that most spatially modulated granule cells contribute to orthogonal representations of distinct spatial contexts.
Topics: Mice; Animals; Mossy Fibers, Hippocampal; Dentate Gyrus; Hippocampus; Place Cells
PubMed: 37043350
DOI: 10.1016/j.celrep.2023.112334