Anatomy and Function of the Primate Entorhinal Cortex

2020 ◽  
Vol 6 (1) ◽  
pp. 411-432 ◽  
Author(s):  
Aaron D. Garcia ◽  
Elizabeth A. Buffalo
Keyword(s):  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Hippocampal Formation ◽  
Physical Space ◽  
Visual Space ◽  
Critical Element ◽  
Memory Processing ◽  
Major Player ◽  
Hippocampus Proper ◽  
And Function

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.

scholarly journals Saccade direction encoding in the primate entorhinal cortex during visual exploration

2015 ◽  
Vol 112 (51) ◽  
pp. 15743-15748 ◽  
Author(s):  
Nathaniel J. Killian ◽  
Steve M. Potter ◽  
Elizabeth A. Buffalo
Keyword(s):  
Entorhinal Cortex ◽  
Physical Space ◽  
Visual Space ◽  
Neural Circuitry ◽  
Visual Exploration ◽  
Head Direction ◽  
Free Viewing ◽  
Signaling Mechanisms ◽  
Complex Scenes ◽  
Saccade Direction

We recently demonstrated that position in visual space is represented by grid cells in the primate entorhinal cortex (EC), suggesting that visual exploration of complex scenes in primates may employ signaling mechanisms similar to those used during exploration of physical space via movement in rodents. Here, we describe a group of saccade direction (SD) cells that encode eye movement information in the monkey EC during free-viewing of complex images. Significant saccade direction encoding was found in 20% of the cells recorded in the posterior EC. SD cells were generally broadly tuned and two largely separate populations of SD cells encoded future and previous saccade direction. Some properties of these cells resemble those of head-direction cells in rodent EC, suggesting that the same neural circuitry may be capable of performing homologous spatial computations under different exploratory contexts.

scholarly journals Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease

Biology Open ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. bio056796
Author(s):  
Olayemi Joseph Olajide ◽  
Marcus E. Suvanto ◽  
Clifton Andrew Chapman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Molecular Mechanisms ◽  
Hippocampal Formation ◽  
Selective Vulnerability ◽  
Primary Role ◽  
Cellular Mechanisms ◽  
Molecular Neurodegeneration

ABSTRACTThe entorhinal cortex (EC) is a vital component of the medial temporal lobe, and its contributions to cognitive processes and memory formation are supported through its extensive interconnections with the hippocampal formation. During the pathogenesis of Alzheimer's disease (AD), many of the earliest degenerative changes are seen within the EC. Neurodegeneration in the EC and hippocampus during AD has been clearly linked to impairments in memory and cognitive function, and a growing body of evidence indicates that molecular and functional neurodegeneration within the EC may play a primary role in cognitive decline in the early phases of AD. Defining the mechanisms underlying molecular neurodegeneration in the EC is crucial to determining its contributions to the pathogenesis of AD. Surprisingly few studies have focused on understanding the mechanisms of molecular neurodegeneration and selective vulnerability within the EC. However, there have been advancements indicating that early dysregulation of cellular and molecular signaling pathways in the EC involve neurodegenerative cascades including oxidative stress, neuroinflammation, glia activation, stress kinases activation, and neuronal loss. Dysfunction within the EC can impact the function of the hippocampus, which relies on entorhinal inputs, and further degeneration within the hippocampus can compound this effect, leading to severe cognitive disruption. This review assesses the molecular and cellular mechanisms underlying early degeneration in the EC during AD. These mechanisms may underlie the selective vulnerability of neuronal subpopulations in this brain region to the disease development and contribute both directly and indirectly to cognitive loss.This paper has an associated Future Leader to Watch interview with the first author of the article.

scholarly journals Mouse entorhinal cortex encodes a diverse repertoire of self-motion signals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Caitlin S. Mallory ◽  
Kiah Hardcastle ◽  
Malcolm G. Campbell ◽  
Alexander Attinger ◽  
Isabel I. C. Low ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Medial Temporal Lobe ◽  
Visual Cues ◽  
Neural Circuits ◽  
Sensory Cues ◽  
Medial Entorhinal Cortex ◽  
Representation Of Space ◽  
Self Motion ◽  
Information Streams ◽  
Representations Of Space

AbstractNeural circuits generate representations of the external world from multiple information streams. The navigation system provides an exceptional lens through which we may gain insights about how such computations are implemented. Neural circuits in the medial temporal lobe construct a map-like representation of space that supports navigation. This computation integrates multiple sensory cues, and, in addition, is thought to require cues related to the individual’s movement through the environment. Here, we identify multiple self-motion signals, related to the position and velocity of the head and eyes, encoded by neurons in a key node of the navigation circuitry of mice, the medial entorhinal cortex (MEC). The representation of these signals is highly integrated with other cues in individual neurons. Such information could be used to compute the allocentric location of landmarks from visual cues and to generate internal representations of space.

scholarly journals Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Brain ◽  
2021 ◽  
Author(s):  
David Berron ◽  
Jacob W Vogel ◽  
Philip S Insel ◽  
Joana B Pereira ◽  
Long Xie ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Entorhinal Cortex ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Memory Impairment ◽  
Memory Performance ◽  
Hippocampal Atrophy ◽  
Tau Pathology ◽  
Β Amyloid ◽  
With Memory

Abstract In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.

Postnatal Development of the Hippocampus in Male Albino Rats: A Histomorphometric Study

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A A Baraka ◽  
K A Hafez ◽  
A I A Othman ◽  
A M M Sadek
Keyword(s):  
Dentate Gyrus ◽  
Postnatal Development ◽  
Learning And Memory ◽  
Hippocampal Formation ◽  
Critical Role ◽  
Mammalian Brain ◽  
Albino Rats ◽  
Ammon's Horn ◽  
Hippocampus Proper ◽  
Ammon’S Horn

Abstract Introduction In recent year deterioration in cognitive, learning, and memory become one of the significant problems in human life. Hippocampus is a pivotal part of the brain’s limbic system which serves a critical role in memory, learning process and regulating the emotions. In most regions of the brain, neurons are generated only at specific periods of early development, and not born in the adulthood. In contrast, hippocampal neurons are generated throughout development and adult life. The hippocampal dentate gyrus was reported to be one of the few regions of the mammalian brain where neurogenesis continue to occur throughout adulthood. The neurogenesis in the dentate gyrus was thought to play an important role in hippocampus-dependent learning and memory. The hippocampal formation is composed of the hippocampus proper, the dentate gyrus and the subiculum. The hippocampus proper is the largest part and is subdivided into fields designated as Cornu Ammonis or Ammon’s horn (CA) from CA1 to CA4. Ammon's horn is continuous with the subiculum, which acts as the main output source of the hippocampal formation. Aim of the Study To study the postnatal development of the hippocampal formation. Materials and Methods Five male albino rats from the following postnatal ages day 1, week 1, week 2, week3 and week 4 were studied by histological, immunohistochemical, and morphometric methods. Results The general architecture of the hippocampus proper with its polymorphic, pyramidal, and molecular layers was present at day1, whereas the details of the adult structure appeared at week 2. In the dentate gyrus, distinct lamination appeared at week 1 and its maturation continued with the production of neurons at the interhilar zone that peaked at week 2. The number and density of pyramidal axons and dendrites increase by age. Astrocytes increased in size and staining affinity for glial filaments, and acquired a stellate shape with age. Furthermore, the number of granule cell layers increased concomitantly with the increase in thickness of the molecular and polymorphic layers of both the hippocampus proper and the dentate gyrus. Conclusion The important sequences of events in the growth and maturation of the hippocampal formation in male albino rat occurred in the first 2 postnatal weeks.

scholarly journals Hippocampal–diencephalic–cingulate networks for memory and emotion: An anatomical guide

2017 ◽  
Vol 1 ◽  
pp. 239821281772344 ◽  
Author(s):  
Emma J. Bubb ◽  
Lisa Kinnavane ◽  
John P. Aggleton
Keyword(s):  
Prefrontal Cortex ◽  
Medial Temporal Lobe ◽  
Current Knowledge ◽  
Hippocampal Formation ◽  
Retrosplenial Cortex ◽  
Thalamic Nuclei ◽  
Mammillary Bodies ◽  
Individual Site ◽  
Multi Stage ◽  
Anterior Thalamic Nuclei

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus.

scholarly journals Hippocampal Contributions to Episodic Encoding: Insights From Relational and Item-Based Learning

2002 ◽  
Vol 88 (2) ◽  
pp. 982-990 ◽  
Author(s):  
Lila Davachi ◽  
Anthony D. Wagner
Keyword(s):  
Working Memory ◽  
Medial Temporal Lobe ◽  
Memory Formation ◽  
Relational Processing ◽  
Behavioral Measures ◽  
Fmri Study ◽  
Episodic Encoding ◽  
Hippocampus Proper ◽  
Temporal Structures ◽  
Cortical Regions

The integrity of the hippocampus and surrounding medial-temporal cortices is critical for episodic memory, with the hippocampus being posited to support relational or configural associative learning. The present event-related functional magnetic resonance imaging (fMRI) study investigated the role of specific medial-temporal lobe structures in learning during relational and item-based processing, as well as the extent to which these structures are engaged during item-based maintenance of stimuli in working memory. fMRI indexed involvement of the hippocampus and underlying cortical regions during performance of two verbal encoding conditions, one that required item-based maintenance of word triplets in working memory and the other that entailed the formation of inter-item associations across the words in each triplet. Sixteen subjects were scanned using a rapid event-related fMRI design while they encountered the item-based and relational processing trials. To examine the correlation between fMRI signal in medial-temporal structures during learning and the subject's subsequent ability to remember the stimuli (a measure of effective memory formation), subjects were administered a yes-no recognition memory test following completion of the encoding scans. Results revealed that the hippocampus proper was engaged during both relational and item-based processing, with relational processing resulting in a greater hippocampal response. By contrast, entorhinal and parahippocampal gyri were differentially engaged during item-based processing, providing strong evidence for a functional neuroanatomic distinction between hippocampal and parahippocampal structures. Analysis of the neural correlates of subsequent memory revealed that activation in the bilateral hippocampus was reliably correlated with behavioral measures of effective memory formation only for those stimuli that were encoded in a relational manner. Taken together, these data provide evidence that the hippocampus, while engaged during item-based working memory maintenance, differentially subserves the relational binding of items into an integrated memory trace so that the experience can be later remembered.

scholarly journals Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit

2022 ◽  
Author(s):  
Olesia M Bilash ◽  
Spyridon Chavlis ◽  
Panayiota Poirazi ◽  
Jayeeta Basu
Keyword(s):  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Environmental Cues ◽  
Memory Processing ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spikes ◽  
Hippocampal Area ◽  
Insight Into

The lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.

scholarly journals Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Information Transfer ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Dentate Granule Cells ◽  
Hippocampus Proper ◽  
Receptor Plasticity ◽  
Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

scholarly journals Characterization of the hemodynamic response of the hippocampal and parahippocampal regions using FMRI

2021 ◽  
Author(s):  
Priyanka Mehta
Keyword(s):  
Spatial Memory ◽  
Medial Temporal Lobe ◽  
Dominant Role ◽  
Memory Task ◽  
Hemodynamic Response ◽  
Hemodynamic Responses ◽  
Memory Processing ◽  
Time To Peak ◽  
Hemodynamic Characteristics ◽  
The Right

Previous neuroimaging studies have suggested a dominant role of the right medial temporal lobe (MTL) structures- the hippocampal and parahippocampal regions in spatial memory processing. However, the underlying physiological hemodynamic response functions (HRF) of the MTL substructures remain undefined. Given the neuroanatomical differences between these substructures, it is posited that their hemodynamic characteristics are distinct. In this study, the hemodynamic responses of the MTL substructures are investigated using an optimization algorithm that penalizes the curvature (i.e. second derivative) of HRF. The time-to-peak characteristic of the hemodynamic responses revealed that the right CA3 and DG subfields of the hippocampus are significantly more active than the right CA1 subfield during a specific spatial memory task. Further, the hemodynamic responses of the entorhinal, perirhinal and parahippocampal cortices are presented. Together, these findings may help advance our understanding of neurodegenerative diseases like epilepsy and Alzheimer’s disease that are strongly associated to hippocampal dysfunction.

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