Control of voluntary and optogenetically perturbed locomotion by spike rate and timing of neurons of the mouse cerebellar nuclei

Abstract

Neurons of the cerebellar nuclei (CbN), which generate cerebellar output, are inhibited by Purkinje cells. With extracellular recordings during voluntary locomotion in head-fixed mice, we tested how the rate and coherence of inhibition influence CbN cell firing and well-practiced movements. Firing rates of Purkinje and CbN cells were modulated systematically through the stride cycle (~200–300 ms). Optogenetically stimulating ChR2-expressing Purkinje cells with light steps or trains evoked either asynchronous or synchronous inhibition of CbN cells. Steps slowed CbN firing. Trains suppressed CbN cell firing less effectively, but consistently altered millisecond-scale spike timing. Steps or trains that perturbed stride-related modulation of CbN cell firing rates correlated well with irregularities of movement, suggesting that ongoing locomotion is sensitive to alterations in modulated CbN cell firing. Unperturbed locomotion continued more often during trains than steps, however, suggesting that stride-related modulation of CbN spiking is less readily disrupted by synchronous than asynchronous inhibition.