A cortico-subcortical loop for motor control via the pontine reticular formation.

Movement and locomotion are controlled by large neuronal circuits like the cortex-basal ganglia (BG)-thalamus loop. Besides the inhibitory thalamic output, the BG directly control movement via specialized connections with the brainstem. Whether other parallel loops with similar logic exist is presently unclear. Here, we demonstrate that the secondary motor and cingulate cortices (M2/Cg) target and strongly control the activity of glycine transporter 2-positive (GlyT2+) cells in the pontine reticular formation (PRF). In turn, PRF/GlyT2+ cells project to and powerfully inhibit the intralaminar/parafascicular nuclei of the thalamus (IL/Pf). M2/Cg cells co-innervate PRF/GlyT2+ cells and the IL/Pf. Thalamus-projecting PRF/GlyT2+ cells target ipsilateral subcortical regions distinct from BG targets. Activation of the thalamus-projecting PRF/GlyT2+ cells leads to contralateral turning. These results demonstrate that the PRF is part of a cortico-subcortical loop that regulates motor activity parallel to BG circuits. The cortico-PRF-thalamus loop can control turning synergistically with the BG loops via distinct descending pathways.