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. Inhibitory output of the BG loop can directly control movement via specialized connections with the brainstem. Whether other parallel loops with similar logic exist is presently unclear. Here we demonstrate that glycine transporter 2-positive (GlyT2+) cells of the pontine reticular formation (PRF) receive cortical inputs and in turn innervate the thalamus. Thalamus-projecting GlyT2+ cells innervate subcortical regions distinct from BG targets. Cortical cells co-innervate PRF/GlyT2+ cells and thalamus as in the BG loops. Cortex exerts strong excitatory control on PRF/GlyT2+ cells and these neurons powerfully inhibit their thalamic targets. Activation of 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 the BG circuits. The cortico-PRF-thalamus loop can synergistically control turning with the BG loops via distinct descending pathways.