Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex

The mammalian motor system is organized around distinct sub-cortical subsystems, suggesting that intracortical circuits immediately upstream of spinal cord and basal ganglia might be functionally differentiated, too. Here, we show that the main excitatory pathway within mouse motor cortex, layer 2/3→5, is fractionated into distinct pathways targeting corticospinal and corticostriatal neurons, key cell classes involved in motor control. However, connections were selective for neurons in certain sub-layers: corticospinal neurons in upper layer 5B, and corticostriatal neurons in lower 5A. A simple structural combinatorial principle accounts for this highly specific functional circuit architecture: potential connectivity is established by neuronal sub-layer positioning, and actual connectivity within this framework is determined by long-range axonal projection targets. Thus, intracortical circuits of these pyramidal neurons are specified not only by their long-range axonal targets, or their layer or sub-layer positions, but by both, in specific combinations.