Abstract
The frontal cortex plays an important role in the initiation and execution of movements via widespread projections to various cortical and subcortical areas. Layer 2/3 (L2/3) pyramidal cells in the frontal cortex send axons mainly to other ipsilateral/contralateral cortical areas. Subpopulations of layer 5 (L5) pyramidal cells that selectively project to the pontine nuclei or to the contralateral cortex [commissural (COM) cells] also target diverse and sometimes overlapping ipsilateral cortical areas. However, little is known about target area-dependent participation in ipsilateral corticocortical (iCC) connections by subclasses of L2/3 and L5 projection neurons. To better understand the functional hierarchy between cortical areas, we compared iCC connectivity between the secondary motor cortex (M2) and adjacent areas, such as the orbitofrontal and primary motor cortices, and distant non-frontal areas, such as the perirhinal and posterior parietal cortices. We particularly assessed the laminar distribution of iCC cells and fibers, and identified the subtypes of pyramidal cells participating in those projections. For connections between M2 and frontal areas, L2/3 and L5 cells in both areas contributed to reciprocal projections, which can be viewed as “bottom-up” or “top-down” on the basis of their differential targeting of cortical lamina. In connections between M2 and non-frontal areas, neurons participating in bottom-up and top-down projections were segregated into the different layers: bottom-up projections arose primarily from L2/3 cells, while top-down projections were dominated by L5 COM cells. These findings suggest that selective participation in iCC connections by pyramidal cell subtypes lead to directional connectivity between M2 and other cortical areas. Based on these findings, we propose a provisional unified framework of interareal hierarchy within the frontal cortex, and discuss the interaction of local circuits with long-range interareal connections.
Highlights
Unlike cortical neurons in primary sensory areas, neurons in the frontal cortex can sustain persistent activity to encode specific information without external inputs, which may be supported by excitatory reverberation of (i) local recurrent connections among pyramidal cells; (ii) thalamocortical loops strongly influenced by the basal ganglia and cerebellum; and (iii) reciprocal interareal loops (Wang, 2001; Arnsten et al, 2012)
MULTIPLE PYRAMIDAL CELL SUBTYPES IN THE RAT FRONTAL CORTEX The rat frontal cortical layers can be further divided into several sublayers by the size and density of neuronal somata, calbindin expression, thalamic fiber density, and Ctip2 expression (Figure 1A; Ueta et al, 2013)
layer 5 (L5) pyramidal cells consist primarily of Ctip2-positive CPn cells and Ctip2-negative COM cells (Arlotta et al, 2005; Ueta et al, 2013). The proportion of these two major subtypes in the M2 area changed according to depth within L5: both subtypes were abundant in L5a and upper L5b, but in lower L5b, Ctip2-positive cells predominated, suggesting that CPn cells are more prevalent in the lower half of L5b (Figure 2A)
Summary
Unlike cortical neurons in primary sensory areas, neurons in the frontal cortex can sustain persistent activity to encode specific information without external inputs, which may be supported by excitatory reverberation of (i) local recurrent connections among pyramidal cells; (ii) thalamocortical loops strongly influenced by the basal ganglia and cerebellum; and (iii) reciprocal interareal loops (Wang, 2001; Arnsten et al, 2012). To understand the functional operation of the frontal cortex, it is crucial to reveal the formation rules for its corticocortical connections, as well as the relationships between pyramidal cells sending information to the thalamus, basal ganglia, and cerebellum, and those projecting to various cortical areas (Veinante and Deschênes, 2003). By analogy with the directionality of interareal connection demonstrated between visual cortices, this organization provides an anatomical basis for the “top-down” influence from M2 to M1 and the “bottom-up” influence from M1 to M2 (Coogan and Burkhalter, 1993; Dong et al, 2004)
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