Distinct subpopulations of neurons in the deep cerebellar nuclei regulate limb movements during locomotion

Abstract

The cerebellum controls movement and motor coordination by transmitting integrated sensorimotor signals through the deep cerebellar nuclei (DCN). The Purkinje cells in the cerebellar cortex send modulated signals to a diverse population of cell types within the DCN, but very little is known about how each individual cell type contributes to regulation of motor function. In this study, we identified a genetically defined subpopulation of neurons in the interposed anterior nucleus (IntA). We characterized these neurons and found that based on their electrophysiological and molecular properties, they belong to a subset of glutamatergic neurons within the IntA nucleus. To determine the function of these neurons, we selectively expressed Channelrhodopsin 2 (ChR2) in these neurons and optogenetically activated them while the mice performed locomotor task.

To analyze consequences of the manipulation of neurons in the IntA nucleus on locomotion, we designed a walkway that permits detailed analysis of walking kinematics and concurrent optogenetic manipulation in the mice. We show that photostimulation of these neurons did not disrupt the cadence, stance duration, swing duration, stride length and trajectory length, but significantly increased the y-displacement and y max of ipsilateral limb positioning of the mice. Furthermore, we have selectively expressed ChR2 within glutamatergic neurons of the medial (Med) nucleus and compared the limb kinematics of these mice with those with IntA manipulation. Collectively, photostimulation of glutamatergic neurons in the Med nucleus disrupted almost all the limb kinematics of ipsilateral forelimbs and hindlimbs, different than what was observed for photostimulation of neurons in the IntA nucleus. Our studies revealed that there are molecularly distinct subsets of neurons in the DCN, and that subpopulations of glutamatergic neurons from each subnuclei of the DCN regulates different aspect of limb movement.