Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior

Abstract

Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions like perception, motor planning, action, or sleep. Evidence is accumulating that cerebellar output modulates cortical activity and coherence, but how, when, and where it does so is unclear. We studied activity in and coherence between S1 and M1 cortices during whisker stimulation in the absence and presence of optogenetic Purkinje cell stimulation in crus 1 and 2 of awake mice, eliciting strong simple spike rate modulation. Without Purkinje cell stimulation, whisker stimulation triggers fast responses in S1 and M1 involving transient coherence in a broad spectrum. Simultaneous stimulation of Purkinje cells and whiskers affects amplitude and kinetics of sensory responses in S1 and M1 and alters the estimated S1–M1 coherence in theta and gamma bands, allowing bidirectional control dependent on behavioral context. These effects are absent when Purkinje cell activation is delayed by 20 ms. Focal stimulation of Purkinje cells revealed site specificity, with cells in medial crus 2 showing the most prominent and selective impact on estimated coherence, i.e., a strong suppression in the gamma but not the theta band. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1–M1 phase consistency predominantly via ventrolateral thalamus and M1. Our results indicate that activity of sensorimotor cortices can be dynamically and functionally modulated by specific cerebellar inputs, highlighting a widespread role of the cerebellum in coordinating sensorimotor behavior.

Purkinje cells translate subjective salience into readiness to act and choice performance

“…Changing SS firing during the no-lick period affects choice performance and licking Given that SS firing during the no-lick period was associated with choice, and as SS firing in crus 1 and 2 is related to licking (Bryant et al, 2010), we addressed whether a change in SS firing could affect lick timing as well as choice performance. Pcp2-ChR2 mice have PC-specific expression Channelrhodopsin, allowing optogenetic SS stimulation and creating transient disruption of cerebellar nucleus neuron firing (Figures S6A and S6E) (Romano et al, 2018;Witter et al, 2013;Lindeman et al, 2021).…”

Causal evidence for a cerebellar role in prefrontal-hippocampal interaction in spatial working memory decision-making

“…We propose that the cerebellum contributes to the cognitive process of SWM decision-making by optimizing the task-related modulation of mPFC-dCA1 gamma coherence. A proposed role of the cerebellum in optimizing task related coherence between frontal cortical areas and hence optimizing neuronal communication in a task related manner is also supported by experimental evidence in the sensorimotor domain (Lindeman et al, 2021;Popa et al, 2013). Popa et al showed that inhibiting cerebellar output from the interposed nuclei in awake, head fixed mice reduced gamma coherence between sensory and motor cortical areas (Popa et al, 2013).…”

“…Popa et al showed that inhibiting cerebellar output from the interposed nuclei in awake, head fixed mice reduced gamma coherence between sensory and motor cortical areas (Popa et al, 2013). Lindeman and colleagues demonstrated cerebellar involvement in a task related modulation of theta and gamma coherence between sensory and motor areas involved in active whisker movements (Lindeman et al, 2021).…”

Portable Neuroimaging Guided Non-invasive Brain Stimulation of Cortico-cerebello-thalamo-cortical Loop in Substance Use Disorder

“…Cerebello-hippocampal connections have been found via the ventrolateral and laterodorsal thalamus in mice (Bohne et al, 2019) that needs further investigation in humans. However, for our computational simulation based on a published model (Yousif et al, 2020), we postulated an effect of cerebellar tES on substance-seeking triggered by substance-associated cues since interactions between sensory and motor cortices can be modulated by the cerebellum (Lindeman et al, 2021). While ctDCS of the DCN induced gamma oscillations (top panel of Figure 9), bottom panel of the Figure 9 shows that tTIS of the DCN at 63Hz amplitude modulation could lead to gamma-to-beta frequency shift.…”