Distinct local and brain-wide networks are activated by layer-specific optogenetic stimulations of motor cortex
Abstract Primary motor cortex consists of a stack of interconnected but distinct layers, and plays a prominent role in motor control through large-scale networks. However, differential effects of M1 layer-specific functional pathways remain elusive, especially at the macroscopic and mesoscopic scales. Here, we combined layer-specific Cre-driver mouse lines, optogenetics, and fMRI with electrophysiological recordings to identify distinct M1 layer-specific networks. Neuronal activities initiated in L2/3 were mainly confined within M1, while stimulation of L4, L5, and L6 evoked distinct responses in M1 and motor-related subcortical regions, including the striatum and motor thalamus. Although motor cortex has long been considered agranular (without L4), our results structurally, functionally, and neurovascularly confirm the presence of L4. We also find that layer-specific fMRI responses closely couple with laminar electrophysiological recordings. Overall, our results elucidate distinct brain-wide neural archetypes of M1 layer-specific cortical circuits that provide important insights in uncovering the motor system architecture.