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.

Cerebello-Thalamic Spike Transfer via Temporal Coding and Cortical Adaptation

“…Such pauses are found during several behavioral paradigms (Ohmae et al 2013;Ten Brinke et al 2017). For instance, during natural running on a treadmill the CN firing rate rises above 100 Hz during the lift of the paw and decreases sharply during the 100 ms before paw movement (Sarnaik and Raman 2018). According to our in-vitro findings, the transfer of cerebellar information from thalamus to cortex is attenuated during high-frequency CN activity, but can be relayed after the induction of initial spikes that follow a pause in CN spiking.…”

“…Even though our in-vitro study can only assess the impact of synchronously activated cerebellar input with a limited maximum stimulus frequency (ChR2-stimulation of CN axons above 50 Hz resulted in failure to elicit neurotransmitter release; data not shown), the low-pass filter function within the thalamus suggests that cerebellar output is inversely encoded in VL. Whether the debated rebound spiking of CN neurons following a climbing fiber-mediated pause provides a significant contribution to thalamic information processing remains to be investigated (Gauck and Jaeger 2000;Alviña et al 2008;Hoebeek et al 2010;Bengtsson et al 2011;Person and Raman 2011;Dykstra et al 2016;Sarnaik and Raman 2018). Still, the properties that we describe in the current study already show that VL neurons translate the high-frequency cerebellar spiking pattern into a temporally sparse but precise and movement related code, which may serve to fine-tune the information processing in motor cortex.…”

“…Stimulating CN fibers at 20, 35 and 50 Hz resulted in a short-term decrease of EPSC amplitudes P=0.0625, Wilcoxon-signed rank (WCR) test, n=25; Supplementary Figure 2K-M). Next, we tested the thalamic response to brief pauses in the CN stimulation, which commonly occur during motor behaviors (Antziferova et al 1980;Armstrong and Edgley 1984;Ohmae et al 2013;Sarnaik and Raman 2018).…”

“…At rest, the baseline firing rates of CN range between 30 and 100 Hz (Hoebeek et al 2010), while VL and cortical L6 neurons fire at low frequencies between 5 and 20 Hz (Lamarre et al 1971;Vitek et al 1994;Beloozerova et al 2003;Marlinski et al 2012;Olsen et al 2012;Proville et al 2014). Once movement execution starts, CN neurons evolve into phasic patterns including high-frequency bursts of spiking (Antziferova et al, 1980;Armstrong and Edgley, 1984;Ohmae et al, 2013;Sarnaik and Raman, 2018). The well-timed and rapid alterations in CN activity patterns are destined to adapt thalamo-cortical spiking in VL (Proville et al, 2014).…”

Spatial and temporal locomotor learning in mouse cerebellum

“…The ability to localize split-belt adaptation to such a relatively small cerebellar subregion is perhaps surprising in the context of the widespread representation of sensorimotor signals associated with locomotion across the cerebellum (Armstrong and Edgley, 1984;Armstrong et al, 1988;Edgley and Lidierth, 1988;Marple-Horvat and Criado, 1999;Ozden et al, 2012;Powell et al, 2011;Sarnaik and Raman, 2018;Udo et al, 1981). Indeed, many cerebellar regions contribute to locomotion in various ways.…”