• action control
• midbrain
• motor control
• neuronal circuits

The mesencephalic locomotor region (MLR) has been discovered through electrical stimulation experiments for its ability to generate coordinated locomotion and other full-body movements. Different studies have identified excitatory neurons as the key player in generating these effects, nonetheless the real function of these neurons is still unknown. Clinical trials for Deep Brain Stimulation (DBS) targeting the MLR in drug-resistant Parkinson’s disease have recently yielded controversial results, highlighting the functional complexity of this brainstem region.
Here, we functionally dissect two distinct motor pathways arising in the MLR, projecting to the basal ganglia and spinal cord, harnessing genetics, intersectional viral targeting, deep brain imaging and optogenetic tools. MLR neurons with spinal projections are in control of full-body movement, particularly trunk extension. MLR neurons with ascending projections to the basal ganglia output nuclei display complex activity patterns during forelimb and orofacial behaviors and, through their widespread synaptic targets, holistically regulate movement.
Altogether, our findings reveal the existence of functionally segregated neuronal subpopulations within the MLR and suggest that this diversity explains controversial findings in basic research on motor control and in the clinical investigation of movement disorders.