Distinct Contributions of Mesencephalic Locomotor Region Nuclei to Locomotor Control in the Freely Behaving Mouse

The mesencephalic locomotor region (MLR) has been initially identified as a supraspinal center capable of initiating and modulating locomotion. Whereas its functional contribution to locomotion has been widely documented throughout the phylogeny from the lamprey to humans, there is still debate about its exact organization. Combining kinematic and electrophysiological recordings in mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus initiate locomotion and induce running gaits, whereas glutamatergic and cholinergic neurons of the pedunculopontine nucleus modulate locomotor pattern and rhythm, contributing to slow-walking gaits. By initiating, modulating, and accelerating locomotion, our study identifies and characterizes distinct neuronal populations of this functional region important to locomotor command. •Only long photoactivation of glutamatergic CnF initiates locomotion•Short activation of glutamatergic CnF and PPN modifies locomotor pattern•Long activation of glutamatergic CnF resets rhythm and induces running gaits•Only long photoinhibition of glutamatergic PPN stops locomotion Using mouse genetics, Josset, Roussel, et al. characterize the functional contribution of midbrain neurons to locomotion. Photostimulation of glutamatergic CnF neurons initiate and accelerate locomotion, whereas glutamatergic and cholinergic PPN contribute to slow-walking gaits and locomotor arrests.