Neuronal chemo‐architecture of the entorhinal cortex: A comparative review

Kobro‐Flatmoen, Asgeir

doi:10.1111/ejn.14511

Cited by 33 publications

(53 citation statements)

References 183 publications

(579 reference statements)

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“…The main counterparts in Layer II of MEC are the calbindin‐positive pyramidal neurons. In LEC, a comparable subdivision has been reported with fan and multipolar neurons forming a substantial part of the reelin‐positive principal cells and pyramidal neurons corresponding largely to calbindin‐positive neurons (for review see Kobro‐Flatmoen & Witter, ; Witter et al, ). In MEC, these two main principal cell types can also be distinguished based on their electrophysiological profiles.…”

Section: Introductionmentioning

confidence: 58%

“…For this review we will use LEC and MEC as indications for two areas, irrespective of species, for which most functional data are available, including in humans (Maass, Berron, Libby, Ranganath, & Duzel, ; Montchal et al, ; Navarro Schroder, Haak, Zaragoza Jimenez, Beckmann, & Doeller, ). Moreover, in a recent comparative review on the distribution of chemically defined neurons and neuropil, we have argued that these are best described as a gradient related to the distance from the rhinal/collateral sulcus and not related to any of the traditional cytorarchitectural subdivisions (Kobro‐Flatmoen & Witter, ).…”

Section: Introductionmentioning

confidence: 99%

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Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

et al. 2019

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In this review, we aim to reappraise the organization of intrinsic and extrinsic networks of the entorhinal cortex with a focus on the concept of parallel cortical connectivity streams. The concept of two entorhinal areas, the lateral and medial entorhinal cortex, belonging to two parallel input–output streams mediating the encoding and storage of respectively what and where information hinges on the claim that a major component of their cortical connections is with the perirhinal cortex and postrhinal or parahippocampal cortex in, respectively, rodents or primates. In this scenario, the lateral entorhinal cortex and the perirhinal cortex are connectionally associated and likewise the postrhinal/parahippocampal cortex and the medial entorhinal cortex are partners. In contrast, here we argue that the connectivity matrix emphasizes the potential of substantial integration of cortical information through interactions between the two entorhinal subdivisions and between the perirhinal and postrhinal/parahippocampal cortices, but most importantly through a new observation that the postrhinal/parahippocampal cortex projects to both lateral and medial entorhinal cortex. We suggest that entorhinal inputs provide the hippocampus with high‐order complex representations of the external environment, its stability, as well as apparent changes either as an inherent feature of a biological environment or as the result of navigating the environment. This thus indicates that the current connectional model of the parahippocampal region as part of the medial temporal lobe memory system needs to be revised.

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Section: Introductionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

et al. 2019

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“…The transentorhinal region and the EC, hubs for integrating information from hippocampal, cortical and subcortical regions 35 , are the first cortical fields to accumulate tau-positive neurofibrillary inclusions followed by neuronal loss in AD 3 . The transentorinal region is first affected in Braak stage 1, followed by the EC in Braak stage 2.…”

Section: Discussionmentioning

confidence: 99%

“…The transentorinal region is first affected in Braak stage 1, followed by the EC in Braak stage 2. The EC is a relatively phylogenetically conserved brain structure in mammals 35,57 . The rodent EC can be subdivided into medial and lateral portions based on cytoarchitectonics and projections.…”

Section: Discussionmentioning

confidence: 99%

“…2a-d). These subpopulations exhibited distinct expression of EC layer-specific genes identified in the mouse medial EC 34 , which phylogenetically resembles the human caudal EC 35,36 . Notably, subpopulation EC:Exc.s2 showed a striking ~50% decrease in its relative abundance in Braak stage 2 compared to Braak stage 0, with no further decrease in Braak stage 6 ( Fig.…”

Section: Selective Vulnerability Of Excitatory Neuron Subpopulationsmentioning

confidence: 92%

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Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease

Leng

Eser

et al. 2020

Preprint

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Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus -brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively -from individuals spanning the neuropathological progression of AD. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. MAIN TEXTSelective vulnerability is a fundamental feature of neurodegenerative diseases, in which different neuronal populations show a gradient of susceptibility to degeneration 1, 2 . Selective vulnerability at the network level has been extensively explored in Alzheimer's disease (AD) 3-5 , currently the leading cause of dementia and lacking in effective therapies. However, little is known about the mechanisms underlying selective vulnerability at the cellular level in AD, which could provide insight into disease mechanisms and lead to therapeutic strategies.The entorhinal cortex (EC), an allocortex, is one of the first cortical brain regions to exhibit neuronal loss in AD 6 . Neurons in the external EC layers, especially in layer II (also known as alpha clusters of the lamina principalis externa, abbreviated "Pre-alpha") 7 , accumulate taupositive neurofibrillary changes and die early on in the course of AD 8-13 . However, these selectively vulnerable neurons have yet to be characterized extensively at the molecular level. Furthermore, it is unknown whether there are differences in vulnerability among subpopulations of these neurons. Although rodent models of AD have offered some insights [14][15][16] , the human brain has unique features with regard to cellular physiology, composition and aging [17][18][19] , limiting the extrapoloation of findings from animal models to address selective vulnerability.Previous studies have combined laser capture microdissection with microarray analysis of gene expression 20, 21 to characterize EC neurons in AD, but focused on disease-related changes in gene expression, rather than selective vulnerability. More recently, single-nucleus RNA-sequencing (snRNA-seq) has enabled large-scale characterization of transcriptomic profiles of individual cells from post-mortem human brain tissue 22, 23 . However, snRNA-seq studies of AD p...

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2020

Hippocampus

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Neuronal chemo‐architecture of the entorhinal cortex: A comparative review

Cited by 33 publications

References 183 publications

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease

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