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Progress in Brain Research 2007The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the... (Review)
Review
The dentate gyrus is a simple cortical region that is an integral portion of the larger functional brain system called the hippocampal formation. In this review, the fundamental neuroanatomical organization of the dentate gyrus is described, including principal cell types and their connectivity, and a summary of the major extrinsic inputs of the dentate gyrus is provided. Together, this information provides essential information that can serve as an introduction to the dentate gyrus--a "dentate gyrus for dummies."
Topics: Animals; Dentate Gyrus; Neuroanatomy; Neurons
PubMed: 17765709
DOI: 10.1016/S0079-6123(07)63001-5 -
Cell Stem Cell Apr 2018Adult hippocampal neurogenesis declines in aging rodents and primates. Aging humans are thought to exhibit waning neurogenesis and exercise-induced angiogenesis, with a...
Adult hippocampal neurogenesis declines in aging rodents and primates. Aging humans are thought to exhibit waning neurogenesis and exercise-induced angiogenesis, with a resulting volumetric decrease in the neurogenic hippocampal dentate gyrus (DG) region, although concurrent changes in these parameters are not well studied. Here we assessed whole autopsy hippocampi from healthy human individuals ranging from 14 to 79 years of age. We found similar numbers of intermediate neural progenitors and thousands of immature neurons in the DG, comparable numbers of glia and mature granule neurons, and equivalent DG volume across ages. Nevertheless, older individuals have less angiogenesis and neuroplasticity and a smaller quiescent progenitor pool in anterior-mid DG, with no changes in posterior DG. Thus, healthy older subjects without cognitive impairment, neuropsychiatric disease, or treatment display preserved neurogenesis. It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience.
Topics: Adolescent; Adult; Aged; Aging; Dentate Gyrus; Hippocampus; Humans; Middle Aged; Neurogenesis; Neurons; Young Adult
PubMed: 29625071
DOI: 10.1016/j.stem.2018.03.015 -
Nature Jul 2018Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to...
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of stress-responsive cells that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience whereas excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.
Topics: Affect; Animals; Calcium; Chronic Disease; Dentate Gyrus; Male; Mice; Neurogenesis; Resilience, Psychological; Stress, Psychological
PubMed: 29950730
DOI: 10.1038/s41586-018-0262-4 -
Frontiers in Neural Circuits 2014
Topics: Animals; Dentate Gyrus; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity
PubMed: 25309334
DOI: 10.3389/fncir.2014.00107 -
Nature Mar 2016Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.
Topics: Aging; Alzheimer Disease; Amnesia; Amyloid beta-Protein Precursor; Animals; Dendritic Spines; Dentate Gyrus; Disease Models, Animal; Early Medical Intervention; Humans; Long-Term Potentiation; Male; Memory, Episodic; Memory, Long-Term; Mice; Mice, Transgenic; Optogenetics; Plaque, Amyloid; Presenilin-1; Synapses; Transgenes; tau Proteins
PubMed: 26982728
DOI: 10.1038/nature17172 -
Progress in Brain Research 2016The dentate gyrus plays critical roles both in cognitive processing, and in regulation of the induction and propagation of pathological activity. The cellular and... (Review)
Review
The dentate gyrus plays critical roles both in cognitive processing, and in regulation of the induction and propagation of pathological activity. The cellular and circuit mechanisms underlying these diverse functions overlap extensively. At the cellular level, the intrinsic properties of dentate granule cells combine to endow these neurons with a fundamental reluctance to activate, one of their hallmark traits. At the circuit level, the dentate gyrus constitutes one of the more heavily inhibited regions of the brain, with strong, fast feedforward and feedback GABAergic inhibition dominating responses to afferent activation. In pathologic states such as epilepsy, a number of alterations within the dentate gyrus combine to compromise the regulatory properties of this circuit, culminating in a collapse of its normal function. This epilepsy-associated transformation in the fundamental properties of this critical regulatory hippocampal circuit may contribute both to seizure propensity, and cognitive and emotional comorbidities characteristic of this disease state.
Topics: Animals; Dentate Gyrus; Epilepsy; GABAergic Neurons; Humans; Membrane Potentials
PubMed: 27323942
DOI: 10.1016/bs.pbr.2016.04.005 -
Progress in Neuro-psychopharmacology &... Aug 2009This article reviews evidence from studies employing colchicine-induced granule cell loss in the adult rat brain, and irradiation-induced hypoplasia of the neonatal... (Review)
Review
This article reviews evidence from studies employing colchicine-induced granule cell loss in the adult rat brain, and irradiation-induced hypoplasia of the neonatal dentate gyrus, on the performance of spatial and non-spatial behavioral tasks. The general picture emerging from this analysis reveals that the dentate gyrus granule cells are critically involved in spatial behavior, particularly when this requires the adoption of place strategies. This notion also provides an explanation for the behavioral effects of dentate gyrus granule cell loss seen in apparently non-spatial tasks.
Topics: Animals; Dentate Gyrus; Humans; Maze Learning; Psychomotor Performance; Space Perception; Spatial Behavior
PubMed: 19375476
DOI: 10.1016/j.pnpbp.2009.03.036 -
Behavioural Brain Research Nov 2019Anatomical observations, theoretical work and lesion experiments have led to the idea that an important function of the dentate gyrus of the mammalian hippocampus is... (Review)
Review
Anatomical observations, theoretical work and lesion experiments have led to the idea that an important function of the dentate gyrus of the mammalian hippocampus is pattern separation, a neural computation that ensures new memories are encoded without interference from previously stored memories that share similar features. The dentate gyrus also exhibits a unique form of neural plasticity that results from the continuous integration of newly born excitatory granule cells, termed adult hippocampal neurogenesis. However, the manner in which adult neurogenesis contributes to dentate gyrus network activity and computations is incompletely understood. Here, we first describe the prevailing models for the role of adult neurogenesis in dentate gyrus network function and then re-evaluate these models in the light of recent findings regarding the in vivo activity of the dentate gyrus and synaptic interactions of adult born granule cells with local circuit components, as well as, inputs, and outputs of the dentate gyrus. We propose that adult neurogenesis provides flexibility for the dentate gyrus to rapidly generate a context specific, distributed representation of important sensory stimuli such as spatial cues, which ultimately gives rise to behavioral discrimination.
Topics: Adult; Animals; Cues; Dentate Gyrus; Hippocampus; Humans; Memory; Nerve Net; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 31377252
DOI: 10.1016/j.bbr.2019.112112 -
Progress in Brain Research 2007In the late 1980s, the finding that the dentate gyrus contains more granule cells in the male than in the female of certain mouse strains provided the first indication... (Review)
Review
In the late 1980s, the finding that the dentate gyrus contains more granule cells in the male than in the female of certain mouse strains provided the first indication that the dentate gyrus is a significant target for the effects of sex steroids during development. Gonadal hormones also play a crucial role in shaping the function and morphology of the adult brain. Besides reproduction-related processes, sex steroids participate in higher brain operations such as cognition and mood, in which the hippocampus is a critical mediator. Being part of the hippocampal formation, the dentate gyrus is naturally involved in these mechanisms and as such, this structure is also a critical target for the activational effects of sex steroids. These activational effects are the results of three major types of steroid-mediated actions. Sex steroids modulate the function of dentate neurons under normal conditions. In addition, recent research suggests that hormone-induced cellular plasticity may play a larger role than previously thought, particularly in the dentate gyrus. Specifically, the regulation of dentate gyrus neurogenesis and synaptic remodeling by sex steroids received increasing attention lately. Finally, the dentate gyrus is influenced by gonadal hormones in the context of cellular injury, and the work in this area demonstrates that gonadal hormones have neuroprotective potential. The expression of estrogen, progestin, and androgen receptors in the dentate gyrus suggests that sex steroids, which could be of gonadal origin and/or synthesized locally in the dentate gyrus, may act directly on dentate cells. In addition, gonadal hormones could also influence the dentate gyrus indirectly, by subcortical hormone-sensitive structures such as the cholinergic septohippocampal system. Importantly, these three sex steroid-related themes, functional effects in the normal dentate gyrus, mechanisms involving neurogenesis and synaptic remodeling, as well as neuroprotection, have substantial implications for understanding normal cognitive function, with clinical importance for epilepsy, Alzheimer's disease and mental disorders.
Topics: Animals; Dentate Gyrus; Gonadal Steroid Hormones; Humans; Sex Characteristics
PubMed: 17765731
DOI: 10.1016/S0079-6123(07)63023-4 -
Cold Spring Harbor Perspectives in... Apr 2016The restriction of adult neurogenesis to only a handful of regions of the brain is suggestive of some shared requirement for this dramatic form of structural plasticity.... (Review)
Review
The restriction of adult neurogenesis to only a handful of regions of the brain is suggestive of some shared requirement for this dramatic form of structural plasticity. However, a common driver across neurogenic regions has not yet been identified. Computational studies have been invaluable in providing insight into the functional role of new neurons; however, researchers have typically focused on specific scales ranging from abstract neural networks to specific neural systems, most commonly the dentate gyrus area of the hippocampus. These studies have yielded a number of diverse potential functions for new neurons, ranging from an impact on pattern separation to the incorporation of time into episodic memories to enabling the forgetting of old information. This review will summarize these past computational efforts and discuss whether these proposed theoretical functions can be unified into a common rationale for why neurogenesis is required in these unique neural circuits.
Topics: Computer Simulation; Dentate Gyrus; Nerve Net; Neural Networks, Computer; Neurogenesis
PubMed: 26933191
DOI: 10.1101/cshperspect.a018960