A MODULAR ORGANIZATION OF THE MOUSE MOTOR CORTEX REVEALED BY ITS SUBCORTICAL PROJECTOME

The motor cortex (MO) coordinates movement through its complex connectivity. However, despite evidence for functionally and anatomically distinct areas, the organizing principles of MO lack consensus. Here we show that the subcortical projections of mouse MO define 16 different modules. These projection-defined modules are characterized by unique combinations of cortico-cortical connectivity and excitatory cell-type composition, delineating two spatial MO axes. Along one axis, primary MO couples reciprocally to the somatosensory cortex and supplementary MO to frontal areas. Along the orthogonal axis, modules are stratified by reciprocal connectivity with the specific somatotopic somatosensory areas, together with well-defined cortex-wide connectivity patterns. The target-specific topography of subcortical projections is also organized along these axes. Subcortical nuclei including the thalamus, striatum and brainstem follow distinct convergence-divergence rules, differentially integrating sensorimotor cortical inputs. Together, this work reveals a logic by which the anatomical architecture of the mouse MO integrates into brainwide neuronal circuits for movement.