Abstract

The entorhinal cortex (EC) is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. Different division schemes including two or many more subdivisions have been proposed, but here we will argue that subdividing EC into two components, the lateral EC (LEC) and medial EC (MEC) might suffice to describe the functional architecture of EC. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. First, we will briefly summarize the cytoarchitectonic differences and differences in hippocampal projection patterns on which the subdivision between LEC and MEC traditionally is based and provide a short comparative perspective. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. Cortical connectivity of MEC is features interactions with areas such as the presubiculum, parasubiculum, retrosplenial cortex (RSC) and postrhinal cortex, all areas that are considered to belong to the “spatial processing domain” of the cortex. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. These areas are likely more involved in processing of object information, attention and motivation. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. Together, these observations suggest that the different phenotypes of both EC subdivisions likely depend on the combination of intrinsic organization and specific sets of inputs. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation.

Highlights

  • The denomination ‘‘entorhinal cortex (EC)’’ (Brodman’s area 28) is based on the fact that it is enclosed by the rhinal sulcus

  • The local network of pyramidal cells (PCs) has been explored using similar methods, and like the stellate cells (SCs) network, very sparse monosynaptic connectivity was detected between PCs. These results suggest that the general principle of disynaptic connectivity as described for the SC network applies to the layer II PCs

  • The comparison of main trends in extrinsic and intrinsic connectivity patterns of medial EC (MEC) and lateral EC (LEC) suggests that the different phenotypes of both EC subdivisions likely depend on the combinatorial effects of small differences in intrinsic organization and substantial differences in extrinsic inputs. This conclusion and the following details are mainly based on studies in rodents, the more sparse data in non-human and human primates seem to support a comparable organization

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Summary

Introduction

The denomination ‘‘entorhinal cortex (EC)’’ (Brodman’s area 28) is based on the fact that it is (partially) enclosed by the rhinal (olfactory) sulcus. Multimodal, as well as highly processed unimodal sensory inputs converge at the level of neurons in the superficial layers of the EC. This input is conveyed by the neurons in layers II and III of EC to all subdivisions of the hippocampal formation (Insausti et al, 2004; van Strien et al, 2009; Cappaert et al, 2014; Strange et al, 2014). Layer V neurons in turn are the main origin of EC projections to widespread cortical and subcortical domains in the forebrain (Rosene and Van Hoesen, 1977; Kosel et al, 1982; Cappaert et al, 2014)

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