Towards a "canonical" agranular cortical microcircuit

Abstract

Based on regularities in the intrinsic microcircuitry of cortical areas, variants of a "canonical" cortical microcircuit have been proposed and widely adopted, particularly in computational neuroscience and neuroinformatics. However, this circuit is founded on striate cortex, which manifests perhaps the most extreme instance of cortical organization, in terms of a very high density of cells in highly differentiated cortical layers. Most other cortical regions have a less well differentiated architecture, stretching in gradients from the very dense eulaminate primary cortical areas to the other extreme of dysgranular and agranular areas of low density and poor laminar differentiation. It is unlikely for the patterns of inter- and intra-laminar connections to be uniform in spite of strong variations of their structural substrate. This assumption is corroborated by reports of divergence in intrinsic circuitry across the cortex. Consequently, it remains an important goal to define local microcircuits for a variety of cortical types, in particular, agranular cortical regions. As a counterpoint to the striate microcircuit, which may be anchored in an exceptional cytoarchitecture, we here outline a tentative microcircuit for agranular cortex. The circuit is based on a synthesis of the available literature on the local microcircuitry in agranular cortical areas of the rodent brain, investigated by anatomical and electrophysiological approaches. A central observation of these investigations is a weakening of interlaminar inhibition as cortical cytoarchitecture becomes less distinctive. Thus, our study of agranular microcircuitry revealed deviations from the well-known "canonical" microcircuit established for striate cortex, suggesting variations in the intrinsic circuitry across the cortex that may be functionally relevant.

Keywords: cytoarchitecture; interlaminar connectivity; intrinsic circuitry; striate cortex; structural variation.

Figure 1

(A) Cytoarchitectonic differentiation varies across the cortex. This lateral view of the human brain shows broad variations in granule cell presence as described by von Economo (2009). (B) Laminar origin and termination patterns of extrinsic cortico-cortical connections vary according to the relative architectonic differentiation of the connected areas. Projection origins (terminations) shift from infragranular to supragranular layers, as the source (target) area becomes more strongly differentiated. This rule results in unilaminar profiles for projections between areas that are unequal in their differentiation, and multilaminar profiles for areas with more similar differentiation. (A) adapted from von Economo (2009), (B) adapted from Barbas and Rempel-Clower (1997).

Figure 2

Interlaminar inhibition varies across mouse cortex. As cytoarchitectonic differentiation becomes weaker, the abundance of interlaminar inhibitory-to-excitatory connectivity decreases. By contrast, intralaminar connectivity, including intralaminar inhibition, appears relatively unchanged (Intra-laminar connections, which are all-to-all, are not shown). Column colors follow the color coding of cytoarchitectonic differentiation in Figure 1: yellow-weakly differentiated cortex to dark green-strongly differentiated cortex. Adapted by permission from Macmillan Publishers Ltd: Kätzel et al. (2011).

Figure 3

(A) Intrinsic circuitry in granular cat striate cortex. Adapted from Potjans and Diesmann (2014) who largely based their diagram on Binzegger et al. (2004). (B) Tentative scheme of intrinsic circuitry in agranular rodent frontal cortex. Intralaminar connectivity in agranular cortex is similar to that in granular cortex, but interlaminar connectivity differs. Column colors follow the color coding of cytoarchitectonic differentiation in Figure 1: yellow-weakly differentiated cortex to dark green-strongly differentiated cortex.