Purkinje Cell Activity Determines the Timing of Sensory-Evoked Motor Initiation

Tsutsumi, Shinichiro; Chadney, Oscar; Yiu, Tin-Long; Bäumler, Edgar; Faraggiana, Lavinia; Beau, Maxime; Häusser, Michael

doi:10.1016/j.celrep.2020.108537

Cited by 25 publications

(40 citation statements)

References 81 publications

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“…shown to control the information encoded by SS activity (Streng, Popa, & Ebner, 2017) in a way that a dynamic relationship between CS and SS is necessary for the initiation of sensory-driven behavior (Tsutsumi et al, 2020). We observed reduced spontaneous CS firing frequency as well as increased irregularity in the SS timing, despite normal SS firing frequency.…”

Section: Cs Have Been Recentlymentioning

confidence: 62%

Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

Fernández

Sánchez-León

Llorente

et al. 2021

Preprint

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Atypical sensory processing is currently included within the diagnostic criteria of autism. The cerebellum is known to integrate sensory inputs of different modalities through its connectivity to the cerebral cortex. Interestingly, cerebellar malformations are among the most replicated features found in postmortem brain of individuals with autism. We studied cerebellar integration of sensory information in a mouse model of autism, knockout for the Cntnap2 gene. Cntnap2 is widely expressed in Purkinje cells and has been recently reported to regulate their morphology. Further, individuals with CNTNAP2 mutations display cerebellar malformations and CNTNAP2 antibodies are associated with a mild form of cerebellar ataxia. Previous studies in this mouse model show an altered cerebellar sensory learning. However, a physiological analysis of cerebellar function has not been performed yet. We studied sensory evoked potentials in cerebellar Crus I/II region upon electrical stimulation of the whisker pad in alert mice and found striking differences between WT and Cntnap2 KO mice. In addition, single-cell recordings identified alterations in both sensory-evoked and spontaneous firing patterns of Purkinje cells. These alterations were accompanied by altered intrinsic properties and morphological features of these neurons. Together, these results indicate that the Cntnap2 mouse model could provide novel insight into the pathophysiological mechanisms of ASD core sensory deficits.

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Section: Cs Have Been Recentlymentioning

confidence: 62%

Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

Fernández

Sánchez-León

Llorente

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…However, as we used small fields of view during our optical recordings, there were generally too few simultaneously active PC dendrites to accurately quantify the level of their synchrony. For this reason, we were unable to determine whether the responsive and unresponsive regions of Crus I and II during task performance corresponded to distinct, functional clusters of PCs that have been shown to be either engaged or not engaged during sensory-driven licking (Tsutsumi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…For delay eyeblink conditioning, cerebellar activity begins ramping in response to sensory cues that predict an immediately impending conditioned response (Giovannucci et al, 2017). Similar ramping of cerebellar activity occurs during other learned behaviors in which sensory cues provide a trigger for movement initiation (Bina et al, 2020;Tsutsumi et al, 2020;Yamada et al, 2019). Neural activity also ramps in the cerebellum during motor planning tasks in which a delay period proceeds an impending deliberate movement (Chabrol et al, 2019;Gao et al, 2018;Wagner et al, 2019).…”

Section: Introductionmentioning

confidence: 91%

“…Although neuronal population activity was densely sampled using multi-electrode silicon probes, we restricted our analysis to PCs because they form the sole channel of output from the cerebellar cortex. We identified putative PCs based on their location, firing characteristics, and size (see Methods; Figure S1) (Tsutsumi et al, 2020).…”

Section: Engagement Of the Cerebellum During Internally Timed Discontinuous Movementsmentioning

confidence: 99%

“…Therefore, to determine the representation of climbing-fiber-induced PC activity during periodically performed discontinuous movements, we used two-photon imaging to measure climbing-fiberevoked dendritic calcium events in PCs expressing the calcium sensor GCaMP6f (Figure 6A). This imaging-based approach is more sensitive in detecting climbing-fiber-evoked activity because it is challenging to reliably distinguish complex spike waveforms in extracellular electrophysiological unit recordings (Sedaghat-Nejad et al, 2021;Tsutsumi et al, 2020). In quiescent mice, individual calcium events were readily apparent in the dendrites of left Crus I and II PCs (Figure 6B), reflecting that climbing fibers continuously bombard PCs at 1-2 Hz (Gaffield et al, 2016;Mukamel et al, 2009;Ozden et al, 2012).…”

Section: Climbing-fiber-induced Pc Activity Increases During Movement Initiationmentioning

confidence: 99%

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

2021

Preprint

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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.

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Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

Lyu

Sun

et al. 2022

Advanced Science

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The cerebellum is involved in encoding balance, posture, speed, and gravity during locomotion. However, most studies are carried out on flat surfaces, and little is known about cerebellar activity during free ambulation on slopes. Here, it has been imaged the neuronal activity of cerebellar molecular interneurons (MLIs) and Purkinje cells (PCs) using a miniaturized microscope while a mouse is walking on a slope. It has been found that the neuronal activity of vermal MLIs specifically enhanced during uphill and downhill locomotion. In addition, a subset of MLIs is activated during entire uphill or downhill positions on the slope and is modulated by the slope inclines. In contrast, PCs showed counter-balanced neuronal activity to MLIs, which reduced activity at the ramp peak. So, PCs may represent the ramp environment at the population level. In addition, chemogenetic inactivation of lobule V of the vermis impaired uphill locomotion. These results revealed a novel micro-circuit in the vermal cerebellum that regulates ambulatory behavior in 3D terrains.

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Purkinje Cell Activity Determines the Timing of Sensory-Evoked Motor Initiation

Cited by 25 publications

References 81 publications

Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

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

Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

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