The cerebellum encodes and influences the initiation and termination of discontinuous movements

Abstract

The cerebellum is hypothesized to represent timing information important for organizing salient motor events during periodically performed discontinuous movements. To provide functional evidence validating this idea, we measured and manipulated Purkinje cell (PC) activity in the lateral cerebellum of mice trained to volitionally elicit periodic bouts of stereotyped licking for regularly allocated water rewards. Overall, PC simple spiking modulated during task performance, ramping prior to both lick-bout initiation and termination, two important motor events delimiting movement cycles. The ramping onset occurred earlier for the initiation of un-cued exploratory licking that anticipated water availability relative to licking that was reactive to water allocation, suggesting that the cerebellum is engaged differently depending on the movement context. In a subpopulation of PCs, climbing-fiber-evoked responses also increased during lick-bout initiation, but not termination, highlighting differences in how cerebellar input pathways represent task-related information. Optogenetic perturbation of PC activity disrupted the behavior in both initiating and terminating licking bouts and reduced the ability of animals to finely time predictive action around reward delivery, confirming a causative role in movement organization. Together, these results substantiate that the cerebellum contributes to the control of explicitly timed repeated motor actions.

Cerebellar associative learning underlies skilled reach adaptation

“…Cspks could be sorted stably across the experiment in 59 of 465 putative PCs, 58 of which had Cspks during the peri-reach window (~1s window centered on reach; see Methods). Cspk probability increased shortly before movement onset, consistent with reports of early synchronized Cspk activity occurring at movement initiation 52–54 , then dropped near steady-state levels (Fig. 2a; p = 3.3 × 10 −5 , F = 2.6, RM one-way ANOVA; mean Cpsk probability vs. −500 ms bin: p = 7.1 × 10 −4 , d = −0.62, Dunnett’s multiple comparisons test).…”

“…By contrast, reaches with early Cspks had no discernable kinematic differences (Fig. S4a,b; N = 8 animals, n = 58 cells; Euclidean distance from session median, No Cspk trials vs. Cspk trials: p = 0.32, W = −257, r = −0.13, Wilcoxon signed rank test; Peak velocity, No Cspk trials vs. Cspk trials: p = 0.75, t = 0.32, d = −0.042, paired t-test), although we cannot rule out changes in reaction time or movement initiation 54,55 .…”

Mechanisms and Consequences of Cerebellar Purkinje Cell Disinhibition in a Mouse Model of Duchenne Muscular Dystrophy

“…Unambiguous PC units were first identified based on the presence of stereotypical complex spikes, as determined by a pause in simple spike firing in the cross-correlation between the isolated simple spiking unit and subsequent complex spike unit (n = 18). We further used spike rates (.40 Hz) and a large spatial distribution of electrical activity across the probe electrodes (more than six separate channels) to identify additional putative PCs (n = 29; Gaffield and Christie, 2021).…”