Modulation of motor behavior by the mesencephalic locomotor region

SUMMARY 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. However, how the differences in connectivity and physiological properties explain their contributions to motor activity is not well known. Here we report that CnF glutamatergic neurons are more electrophysiologically homogeneous than PPN neurons and have mostly short-range connectivity, whereas PPN glutamatergic neurons are heterogeneous and maintain long-range connections, most notably with the basal ganglia. Optogenetic activation of CnF neurons produces short-lasting muscle activation, driving involuntary motor activity. In contrast, PPN neuron activation produces long-lasting increases in muscle tone that reduce motor activity and disrupt gait. Our results highlight biophysical and functional attributes among MLR neurons that support their differential contribution to motor behavior.
In brief Dautan et al. show key differences in the connectivity and physiological properties of neurons of the mesencephalic locomotor region. Although activation of CnF neurons elicits involuntary locomotor responses, activation of PPN neurons increases muscle tone and reduces motor activity, suggesting that PPN encodes a readiness signal that precedes locomotion.
Graphical Abstract