Reciprocal interareal connections to corticospinal neurons in mouse Ml and S2

Primary motor (Ml) and secondary somatosensory (S2) cortices, although anatomically and functionally distinct, share an intriguing cellular component: corticospinal neurons (CSP) in layer 5B. Here, we investigated the long-range circuits of CSPs in mouse forelimb-Ml and S2. We found that interareal projections (S2→7 Ml and Ml→S2) monosynaptically excited pyramidal neurons across multiple layers, including CSPs. Area-specific differences were observed in the relative strengths of inputs to subsets of CSPs and other cell types, but the general patterns were similar. Furthermore, subcellular mapping of the dendritic distributions of these corticocortical excitatory synapses onto CSPs in both areas also showed similar patterns. Because layer 5B is particularly thick in Ml, but not S2, we studied Ml-CSPs at different cortical depths, quantifying their dendritic morphology and mapping inputs from additional cortical (M2, contralateral Ml, and local layer 2/3) and thalamic (VL nucleus) sources. These results indicated that CSPs exhibit area-specific modifications on an otherwise conserved synaptic organization, and that different afferents innervate Ml-CSP dendritic domains in a source-specific manner. In the cervical spinal cord, CSP axons from S2 and Ml partly converged on middle layers, but S2-CSP axons extended further dorsally, and Ml-CSP axons ventrally. Thus, our findings identify many shared features in the circuits of Ml and S2 and show that these areas communicate via mutual projections that give each area monosynaptic access to the other area's CSPs. These interareally yoked CSP circuits may enable Ml and S2 to operate in a coordinated yet differentiated manner in the service ofsensorimotor integration.