What does the anatomical organization of the entorhinal cortex tell us?

Abstract

The entorhinal cortex is commonly perceived as a major input and output structure of the hippocampal formation, entertaining the role of the nodal point of cortico-hippocampal circuits. Superficial layers receive convergent cortical information, which is relayed to structures in the hippocampus, and hippocampal output reaches deep layers of entorhinal cortex, that project back to the cortex. The finding of the grid cells in all layers and reports on interactions between deep and superficial layers indicate that this rather simplistic perception may be at fault. Therefore, an integrative approach on the entorhinal cortex, that takes into account recent additions to our knowledge database on entorhinal connectivity, is timely. We argue that layers in entorhinal cortex show different functional characteristics most likely not on the basis of strikingly different inputs or outputs, but much more likely on the basis of differences in intrinsic organization, combined with very specific sets of inputs. Here, we aim to summarize recent anatomical data supporting the notion that the traditional description of the entorhinal cortex as a layered input-output structure for the hippocampal formation does not give the deserved credit to what this structure might be contributing to the overall functions of cortico-hippocampal networks.

Figure 1

Schematic representation of the overall organization of the entorhinal cortex and its connectivity. (a) Position of the entorhinal cortex and surrounding cortices and hippocampus in the rat left hemisphere. Indicated are the dorsoventral extent of the hippocampus, positions of LEC and MEC, and the approximate position of a representative horizontal section, illustrated in (b). (b) Horizontal section illustrating entorhinal-hippocampal connectivity (see text for more details). (c) and (d) Representation of the topographical arrangement of entorhinal-hippocampal reciprocal connections. A dorsolateral band of entorhinal cortex (magenta) is preferentially connected to the dorsal hippocampus. Increasingly, more ventral and medial bands of entorhinal cortex (purple to blue) are connected to increasingly more ventral levels of the hippocampus. Yellow line in (c) indicates the border between LEC and MEC. (e) Enlarged entorhinal cortex, taken from (c), indicating the main connectivity of different portions of entorhinal cortex. Brain areas preferentially connected to LEC are printed in green, those connected to MEC are in magenta. The color of the arrows indicates preferential connectivity to the dorsolateral-toventromedial bands of entorhinal cortex (magenta or blue, resp.) or that no preferential gradient is present (green).

Figure 2

Summary diagram of the morphology of main cell types in LEC and MEC. (a) Cells in superficial layers I-III. (b) Cells in deep layers IV-VI. See text for more details.

Figure 3

Schematic representation of laminar distribution and synaptic interactions between inputs and principle cells of the entorhinal cortex. Different inputs are represented by color-coded arrows; position of the arrows indicates the main laminar distribution. Circles indicate putative synaptic contacts between inputs and principle cells. Main output connectivity of principle cells is indicated as well. The figure emphasizes the integrative capacity of layer V cells.