Modulation of motor behavior by the mesencephalic locomotor region

Abstract

The mesencephalic locomotor region (MLR) serves as an interface between higher-order motor systems and lower motor neurons. The excitatory module of the MLR is composed of the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF), and their activation has been proposed to elicit different modalities of movement, but how the differences in connectivity and physiological properties explain their contributions to motor activity is not known. Here we report that CnF glutamatergic neurons are electrophysiologically homogeneous and have short-range axonal projections, whereas PPN glutamatergic neurons are heterogeneous and maintain long-range connections, most notably with the basal ganglia. Optogenetic activation of CnF neurons produced fast-onset, involuntary motor activity mediated by short-lasting muscle activation. In contrast, activation of PPN neurons produced long-lasting increases in muscle tone that reduced motor activity and disrupted gait. Our results thus reveal a differential contribution to motor behavior by the structures that compose the MLR.