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).ĮC comprises different subdivisions, charaterized by connectivity with functionally different sets of cortical and subcortical areas in the brain. The hippocampal fields CA1 and subiculum are the main source of projections that return to layer V of EC, with a less dense projection to layers II and III. 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). Multimodal, as well as highly processed unimodal sensory inputs converge at the level of neurons in the superficial layers of the EC.
Today, EC is conceived as the nodal point between the hippocampal formation on the one hand and a variety of cortical areas on the other hand. Cajal was struck by this massive connection and he therefore suggested that the functional significance of the hippocampus had to be related to that of EC or the sphenoidal cortex/angular ganglion, as he called it at that time.
Interest in the EC arose around the turn of the 20th century when Ramón y Cajal, described a peculiar part of the posterior temporal cortex that was strongly connected to the hippocampus by way of the temporo-ammonic tract ( Ramón Y Cajal, 1902 Witter et al., in press). The denomination “entorhinal cortex (EC)” (Brodman’s area 28) is based on the fact that it is (partially) enclosed by the rhinal (olfactory) sulcus. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation. 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. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. These areas are likely more involved in processing of object information, attention and motivation. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. 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. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. 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. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. 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. The entorhinal cortex (EC) is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. 2Division of Systems Neuroscience, Tohoku University Graduate School of Life Science, Sendai, Japan.1Functional Neuroanatomy, KavlI Institute for Systems Neuroscience, Center for Computational Neuroscience, Egil and Pauline Braathen and Fred Kavli Center for Cortical Microcircuits, NTNU Norwegian University of Science and Technology, Trondheim, Norway.