Cornu Ammonis Regions-Antecedents of Cortical Layers?

Abstract

Studying neocortex and hippocampus in parallel, we are struck by the similarities. All three to four layered allocortices and the six layered mammalian neocortex arise in the pallium. All receive and integrate multiple cortical and subcortical inputs, provide multiple outputs and include an array of neuronal classes. During development, each cell positions itself to sample appropriate local and distant inputs and to innervate appropriate targets. Simpler cortices had already solved the need to transform multiple coincident inputs into serviceable outputs before neocortex appeared in mammals. Why then do phylogenetically more recent cortices need multiple pyramidal cell layers? A simple answer is that more neurones can compute more complex functions. The dentate gyrus and hippocampal CA regions-which might be seen as hippocampal antecedents of neocortical layers-lie side by side, albeit around a tight bend. Were the millions of cells of rat neocortex arranged in like fashion, the surface area of the CA pyramidal cell layers would be some 40 times larger. Even if evolution had managed to fold this immense sheet into the space available, the distances between neurones that needed to be synaptically connected would be huge and to maintain the speed of information transfer, massive, myelinated fiber tracts would be needed. How much more practical to stack the "cells that fire and wire together" into narrow columns, while retaining the mechanisms underlying the extraordinary precision with which circuits form. This demonstrably efficient arrangement presents us with challenges, however, not the least being to categorize the baffling array of neuronal subtypes in each of five "pyramidal layers." If we imagine the puzzle posed by this bewildering jumble of apical dendrites, basal dendrites and axons, from many different pyramidal and interneuronal classes, that is encountered by a late-arriving interneurone insinuating itself into a functional circuit, we can perhaps begin to understand why definitive classification, covering every aspect of each neurone's structure and function, is such a challenge. Here, we summarize and compare the development of these two cortices, the properties of their neurones, the circuits they form and the ordered, unidirectional flow of information from one hippocampal region, or one neocortical layer, to another.

Keywords: development; hippocampus; interneurones; neocortex; neocortical columns; neuronal circuitry; pyramidal cells.

Figure 1

Reconstructions of CA2 interneurones filled during intracellular recordings in adult rat hippocampus (from Mercer et al., 2007, 2012). The largest population of interneurones recorded and filled in CA2 were basket cells. Like those in CA1, CA2 basket cells had dendrites that extended through stratum oriens, sometimes entering the alveus, and through stratum radiatum and into stratum lacunosum moleculare. Their axons arbourized extensively in stratum pyramidale and in some, also in very proximal stratum oriens and/or radiatum (wide axonal arbor basket cells). Two distinct subtypes of CA2 basket cells were identified. The first (CA2 narrow dendritic arbor basket cells) resembled those of CA1 with a narrow, aspiny dendritic arbor and axon confined to CA2. In contrast, both the axons and dendrites of the CA2 wide dendritic arbor basket cells, extended into all three CA-subfields and the horizontally oriented, distal dendritic branches were sparsely spiny. Similarly, two subtypes of CA2 bistratified cells were reported, CA2 narrow and wide dendritic arbor bistratified cells. The dendrites of both subtypes extended through stratum oriens and radiatum without entering stratum lacunosum moleculare, those of wide dendritic arbor cells extending further horizontally than is typical of CA1 bistratified cells and becoming sparsely spiny. Bistratified cell axons ramified in both CA2 and proximal CA1, but stopped abruptly at the CA2/CA3 border. The somata of CA2 SP-SR interneurones were found in stratum pyramidale and their dendrites extended to stratum oriens, branched extensively in stratum radiatum, rarely penetrated SLM, but often extended horizontally to CA1 and CA3. Their axons emerged from the soma and arbourized almost exclusively in stratum radiatum of CA2. The axons and dendrites of CA2 stratum radiatum, Reelin-immunopositive interneurones ramified predominantly in CA2 stratum radiatum, with a few axonal branches extending into neighboring regions.