MODULAR ORGANIZATION OF THE PPN-MEDULLA PATHWAYS

The Pedunculopontine nucleus (PPN) is a mesencephalic structure located at the interface between high-order decision centers, such as cortex and basal ganglia, and medullary nuclei involved in movement generation. This strategic positioning places the PPN as an ideal candidate to relay motor planning and decision-related signals to the medulla, supporting the execution of an adapted and synchronized motor output. While the role of the descending pathways targeting the PPN is well documented, the organisation of the glutamatergic PPN projections to medulla nuclei and their role into movement execution remain poorly understood. By using a combination of retrograde tracing, behavioural approaches, single-photon calcium recording in freely moving mice and optogenetic manipulations, we aim to dissect the anatomo-functional role of glutaminergic PPN-medullary nuclei projections into motor control.
We first identified that PPN neurons projecting to medullary nuclei involved in generating locomotion and orofacial movements, belong to distinct neuronal populations with minimal overlap. Consistent with this organization, our calcium recordings revealed that PPN neuron activities correlate specifically with discrete naturalistic behaviours, such as licking, grooming, eating and locomotion. Moreover, we found that optogenetic modulation of the PPN neurons projecting to different brainstem areas selectively affects orofacial or limb movements. Taken together, our findings suggest that PPN-medulla pathways are organized into parallel modules that control a specific pattern of motor outputs. Within this framework, the PPN emerges as a central hub that integrate and relay higher-order commands to select appropriate motor programs.