Motor Cortex Modulates Ipsilateral Limb Movement Through a Direct Cortico-Cerebellar Circuit

Motor cortex is traditionally associated with control of contralateral limb movements via corticospinal and cortico-ponto-cerebellar pathways. However, the contribution of ipsilateral motor cortical outputs on motor control remains unclear. Here, we identify and characterize a distinct population of cortico-cerebellar (C-C) neurons in the motor cortex that form monosynaptic projections to the ipsilateral cerebellar nuclei. The C-C neurons receive preferential local motor cortical inputs and exhibit projection patterns distinct from cortico-pontine projecting neurons. Using in vivo imaging and optogenetic perturbations, we show that these neurons are active during locomotion and transitions of volitional movements. Disruption of the C-C projection severely affects the locomotion and balancing. Interestingly, the C-C pathway is selectively involved in the initiation and coordination of ipsilateral forelimb movements, without affecting contralateral movement kinematics. These findings shed light on a non-canonical cortico-cerebellar pathway that supports ipsilateral motor control, complementing the traditional control mechanisms of the cerebral cortex over the contralateral motor domains.