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International Journal of Molecular... Oct 2021Depression is characterized by impairments in adult neurogenesis. Reduced hippocampal function, which is suggestive of neurogenesis impairments, is associated with... (Review)
Review
Depression is characterized by impairments in adult neurogenesis. Reduced hippocampal function, which is suggestive of neurogenesis impairments, is associated with depression-related phenotypes. As adult neurogenesis operates in an activity-dependent manner, disruption of hippocampal neurogenesis in depression may be a consequence of neural circuitry impairments. In particular, the entorhinal cortex is known to have a regulatory effect on the neural circuitry related to hippocampal function and adult neurogenesis. However, a comprehensive understanding of how disruption of the neural circuitry can lead to neurogenesis impairments in depression remains unclear with respect to the regulatory role of the entorhinal cortex. This review highlights recent findings suggesting neural circuitry-regulated neurogenesis, with a focus on the potential role of the entorhinal cortex in hippocampal neurogenesis in depression-related cognitive and emotional phenotypes. Taken together, these findings may provide a better understanding of the entorhinal cortex-regulated hippocampal neurogenesis model of depression.
Topics: Adult; Animals; Cognition; Depressive Disorder, Major; Emotions; Entorhinal Cortex; Hippocampus; Humans; Neurogenesis
PubMed: 34769155
DOI: 10.3390/ijms222111725 -
Nature Aug 2005The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in...
The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.
Topics: Action Potentials; Animals; Cues; Electrodes; Entorhinal Cortex; Environment; Male; Models, Neurological; Neurons; Orientation; Rats; Rats, Long-Evans; Space Perception
PubMed: 15965463
DOI: 10.1038/nature03721 -
Neuroscience Research Jul 2014The entorhinal cortex is thought to support rapid encoding of new associations by serving as an interface between the hippocampus and neocortical regions. Although the... (Review)
Review
The entorhinal cortex is thought to support rapid encoding of new associations by serving as an interface between the hippocampus and neocortical regions. Although the entorhinal-hippocampal interaction is undoubtedly essential for initial memory acquisition, the entorhinal cortex contributes to memory retrieval even after the hippocampus is no longer necessary. This suggests that during memory consolidation additional synaptic reinforcement may take place within the cortical network, which may change the connectivity of entorhinal cortex with cortical regions other than the hippocampus. Here, I outline behavioral and physiological findings which collectively suggest that memory consolidation involves the gradual strengthening of connection between the entorhinal cortex and the medial prefrontal/anterior cingulate cortex (mPFC/ACC), a region that may permanently store the learned association. This newly formed connection allows for close interaction between the entorhinal cortex and the mPFC/ACC, through which the mPFC/ACC gains access to neocortical regions that store the content of memory. Thus, the entorhinal cortex may serve as a gatekeeper of cortical memory network by selectively interacting either with the hippocampus or mPFC/ACC depending on the age of memory. This model provides a new framework for a modification of cortical memory network during systems consolidation, thereby adding a fresh dimension to future studies on its biological mechanism.
Topics: Entorhinal Cortex; Hippocampus; Humans; Memory; Models, Neurological; Neural Pathways
PubMed: 24642278
DOI: 10.1016/j.neures.2014.02.012 -
Neurobiology of Aging Apr 2022The entorhinal cortex is the site of some of the earliest pathological changes in Alzheimer's disease, including neuronal, synaptic and volumetric loss. Specifically,...
The entorhinal cortex is the site of some of the earliest pathological changes in Alzheimer's disease, including neuronal, synaptic and volumetric loss. Specifically, the lateral entorhinal cortex shows significant accumulation of tau neurofibrillary tangles in the amnestic mild cognitive impairment (aMCI) phase of Alzheimer's disease. Although decreased entorhinal cortex activation has been observed in patients with aMCI in the context of impaired memory function, it remains unclear if functional changes in the entorhinal cortex can be localized to the lateral or medial entorhinal cortex. To assess subregion specific changes in the lateral and medial entorhinal cortex, patients with aMCI and healthy aged-matched control participants underwent high-resolution structural and functional magnetic resonance imaging. Patients with aMCI showed significantly reduced volume, and decreased activation localized to the lateral entorhinal cortex but not the medial entorhinal cortex. These results show that structural and functional changes associated with impaired memory function differentially engage the lateral entorhinal cortex in patients with aMCI, consistent with the locus of early disease related pathology.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Entorhinal Cortex; Humans; Magnetic Resonance Imaging; Memory Disorders
PubMed: 35182842
DOI: 10.1016/j.neurobiolaging.2021.12.008 -
Reviews in the Neurosciences Dec 2022There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a... (Review)
Review
There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a time scale of tens of ms. If such assemblies form an odor representation, then a fundamental question is how each assembly then induces neuronal activity in downstream structures. We have addressed this question in a detailed model of superficial layers of lateral entorhinal cortex, a recipient of input from olfactory cortex and olfactory bulb. Our results predict that the response of the fan cell subpopulation can be approximated by a relatively simple Boolean process, somewhat along the lines of the McCulloch/Pitts scheme; this is the case because of the sparsity of recurrent excitation amongst fan cells. However, because of recurrent excitatory connections between layer 2 and layer 3 pyramidal cells, synaptic and probably also gap junctional, the response of pyramidal cell subnetworks cannot be so approximated. Because of the highly structured anatomy of entorhinal output projections, our model suggests that downstream targets of entorhinal cortex (dentate gyrus, hippocampal CA3, CA1, piriform cortex, olfactory bulb) receive differentially processed information.
Topics: Humans; Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells
PubMed: 35447022
DOI: 10.1515/revneuro-2022-0011 -
Annual Review of Vision Science Sep 2020The entorhinal cortex (EC) is a critical element of the hippocampal formation located within the medial temporal lobe (MTL) in primates. The EC has historically received... (Review)
Review
The entorhinal cortex (EC) is a critical element of the hippocampal formation located within the medial temporal lobe (MTL) in primates. The EC has historically received attention for being the primary mediator of cortical information going into and coming from the hippocampus proper. In this review, we highlight the significance of the EC as a major player in memory processing, along with other associated structures in the primate MTL. The complex, convergent topographies of cortical and subcortical input to the EC, combined with short-range intrinsic connectivity and the selective targeting of EC efferents to the hippocampus, provide evidence for subregional specialization and integration of information beyond what would be expected if this structure were a simple conduit of information for the hippocampus. Lesion studies of the EC provide evidence implicating this region as critical for memory and the flexible use of complex relational associations between experienced events. The physiology of this structure's constituent principal cells mirrors the complexity of its anatomy. EC neurons respond preferentially to aspects of memory-dependent paradigms including object, place, and time. EC neurons also show striking spatial representations as primates explore visual space, similar to those identified in rodents navigating physical space. In this review, we highlight the great strides that have been made toward furthering our understanding of the primate EC, and we identify paths forward for future experiments to provide additional insight into the role of this structure in learning and memory.
Topics: Animals; Entorhinal Cortex; Hippocampus; Memory; Neurons; Primates
PubMed: 32580662
DOI: 10.1146/annurev-vision-030320-041115 -
Frontiers of Neurology and Neuroscience 2014The hippocampus is one of several brain regions that together comprise the hippocampal formation. The hippocampal formation is a prominent C-shaped structure bulging in... (Review)
Review
The hippocampus is one of several brain regions that together comprise the hippocampal formation. The hippocampal formation is a prominent C-shaped structure bulging in the floor of the temporal horn of the lateral ventricle. The hippocampus proper consists of three major subfields (CA1-CA3). The other regions that together comprise the hippocampal formation consist of the dentate gyrus, the subicular complex, and the entorhinal cortex. Based on its extrinsic connectivity, the hippocampal formation receives a vast amount of highly processed multimodal sensory information that is funneled into the hippocampal formation mainly by the entorhinal cortex. The entorhinal cortex is connected to associational neocortical areas in a reciprocal manner. Extensive hippocampal integration of sensory information is established by a largely unidirectional chain of intrinsic hippocampal projections. Our current knowledge on hippocampal connectivity and function is largely based on studies of rodents and monkeys. It still remains to be determined to which extent such neuroanatomical data of experimental animals is applicable to the human hippocampal formation.
Topics: Animals; Entorhinal Cortex; Hippocampus; Humans; Magnetic Resonance Imaging; Neural Pathways
PubMed: 24777126
DOI: 10.1159/000360925 -
Physiological Reviews Apr 2022The hippocampal formation is critically involved in learning and memory and contains a large proportion of neurons encoding aspects of the organism's spatial... (Review)
Review
The hippocampal formation is critically involved in learning and memory and contains a large proportion of neurons encoding aspects of the organism's spatial surroundings. In the medial entorhinal cortex (MEC), this includes grid cells with their distinctive hexagonal firing fields as well as a host of other functionally defined cell types including head direction cells, speed cells, border cells, and object-vector cells. Such spatial coding emerges from the processing of external inputs by local microcircuits. However, it remains unclear exactly how local microcircuits and their dynamics within the MEC contribute to spatial discharge patterns. In this review we focus on recent investigations of intrinsic MEC connectivity, which have started to describe and quantify both excitatory and inhibitory wiring in the superficial layers of the MEC. Although the picture is far from complete, it appears that these layers contain robust recurrent connectivity that could sustain the attractor dynamics posited to underlie grid pattern formation. These findings pave the way to a deeper understanding of the mechanisms underlying spatial navigation and memory.
Topics: Action Potentials; Animals; Entorhinal Cortex; Hippocampus; Humans; Learning; Neurons; Pyramidal Cells
PubMed: 34254836
DOI: 10.1152/physrev.00042.2020 -
Neuron Oct 2022Extensive interhemispheric projections connect many homotopic brain regions, including the hippocampal formation, but little is known as to how information transfer...
Extensive interhemispheric projections connect many homotopic brain regions, including the hippocampal formation, but little is known as to how information transfer affects the functions supported by the target area. Here, we studied whether the commissural projections connecting the medial entorhinal cortices contribute to spatial coding, object coding, and memory. We demonstrate that input from the contralateral medial entorhinal cortex targets all major cell types in the superficial medial entorhinal cortex, modulating their firing rate. Notably, a fraction of responsive cells displayed object tuning and exhibited a reduction in their firing rate upon the inhibition of commissural input. In line with this finding are behavioral results that revealed the contribution of commissural input to episodic-like memory retrieval.
Topics: Entorhinal Cortex; Memory, Episodic; Hippocampus
PubMed: 36084654
DOI: 10.1016/j.neuron.2022.08.013 -
Proceedings of the National Academy of... Feb 2022The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head-direction (HD), border, and object-vector (OV) cells. How...
The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head-direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford. Here, we examined the topographic arrangement of spatially modulated neurons in the superficial layers of MEC and adjacent parasubiculum using miniaturized, portable two-photon microscopes, which allow mice to roam freely in open fields. Grid cells exhibited low levels of co-occurrence with OV cells and clustered anatomically, while border, HD, and OV cells tended to intermingle. These data suggest that grid cell networks might be largely distinct from those of border, HD, and OV cells and that grid cells exhibit strong coupling among themselves but weaker links to other cell types.
Topics: Animals; Brain Mapping; Entorhinal Cortex; Male; Mice; Microscopy; Miniaturization; Motor Activity; Neurons
PubMed: 35135885
DOI: 10.1073/pnas.2121655119