Highly specialized subcortical motor networks govern movement and locomotion. The cortico-basal ganglia (BG)-thalamocortical loop is crucial for movement control, and disruption of BG activity leads to unilateral rotation.We investigated whether the pontine reticular formation (PRF) also participates in a motor-related, cortico-subcortico-thalamocortical loop since PRF sends inhibitory terminals to the intralaminar thalamic nuclei (IL) and parafascicular nucleus (Pf), like BG, both in rodents and humans. We studied the effects of unilateral optogenetic activation of PRF inhibitory cells (PRF/GlyT2+) on locomotor behavior and analyzed the impact of cortical inputs on PRF/GlyT2+ neuronal activity.We found that layer 5 (L5) neurons of higher-order motor cortical areas exert strong glutamatergic control over the PRF/GlyT2+ neuronal activity primarily via synaptic contacts on dendrites. Using anterograde viral tracing, we found that mid-caliber dendrites and spines of PRF/GlyT2+ cells receive L5 inputs from the frontal cortex (M2 and Cingulate) in mice. In vivo juxtacellular recording showed that photoactivation of cortical L5 cells evoked short-latency APs with high probability in PRF/GlyT2+ cells. The same L5 cells innervated PRF and its thalamic targets. Photoactivation of PRF/Glyt2+ neurons led to a significantly decreased firing rate of the IL/Pf cells and resulted in unilateral rotation and movement initiation.Our findings suggest that synchronous frontal cortical activity conveys behavioral signals to PRF, and PRF/GlyT2+ cells can transfer this cortical input as an inhibitory signal to the IL/Pf before they return to the cortex via the thalamocortical pathway. Our results suggest that PRF plays an important role in motor control.