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

Abstract

Coherence among sensory and motor cortices is indicative of binding of critical functions in perception, motor planning, action and sleep. Evidence is emerging that the cerebellum can impose coherence between cortical areas, but how and when it does so is unclear. Here, we studied coherence between primary somatosensory (S1) and motor (M1) cortices during sensory stimulation of the whiskers in the presence and absence of optogenetic stimulation of cerebellar Purkinje cells in awake mice. Purkinje cell activation enhanced and reduced sensory-induced S1-M1 coherence in the theta and gamma bands, respectively. This impact only occurred when Purkinje cell stimulation was given simultaneously with sensory stimulation; a 20 ms delay was sufficient to alleviate its impact, suggesting the existence of a fast, cerebellar sensory pathway to S1 and M1. The suppression of gamma band coherence upon Purkinje cell stimulation was significantly stronger during trials with relatively large whisker movements, whereas the theta band changes did not show this correlation. In line with the anatomical distribution of the simple spike and complex spike responses to whisker stimulation, this suppression also occurred following focal stimulation of medial crus 2, but not of lateral crus 1. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 coherence most prominently via the ventrolateral thalamus and M1. Our results indicate that coherences between sensory and motor cortices in different frequency ranges can be dynamically modulated by cerebellar input, and that the modulation depends on the behavioral context and is site-specific.Significance StatementCoherent activity between sensory and motor areas is essential in sensorimotor integration. We show here that the cerebellum can differentially affect cortical theta and gamma band coherences evoked by whisker stimulation via a fast ascending and predictive pathway. In line with the functional heterogeneity of its modular organization, the impact of the cerebellum is region-specific and tuned to ongoing motor responses. These data highlight site-specific and context-dependent interactions between the cerebellum and the cerebral cortex that can come into play during a plethora of sensorimotor functions.

Abnormal Cerebellar Development in Autism Spectrum Disorders

“…Specifically, neural activity in the cerebellum represents the coherence of neural oscillations between the hippocampus and prefrontal cortex [93], and inhibition of the cerebellar cortex disrupts this coherence and may decrease performance in a memory task [94]. Interestingly, this role of the cerebellum in modulating coherence of multiple brain regions is not restricted to cognitive function, as excitation of Purkinje cells also disrupts phase coherence between the sensory and motor cortices during whisker stimulation [95]. Thus, while these functional studies do not confirm that disruption of cerebellar development causes early-onset cognitive, social, or language impairments directly observed in ASD, they provide compelling evidence that the cerebellum directly modulates brain-wide neural networks involved in highly complex cognitive tasks.…”

Cerebellar Control of a Unitary Head Direction Sense

“…We hypothesized that the cerebellum might play a critical role in processing the information required for stable HD cell activity patterns. Also, since the cerebellum is involved in temporal synchronization between distant structures (Lindeman et al, 2021;Liu et al, 2020;McAfee et al, 2019;Popa et al, 2013), we sought to examine the influence of the cerebellum on the coordination between different HD structures.…”

Cerebellar control of thalamocortical circuits for cognitive function: A review of pathways and a proposed mechanism

“…Importantly, experiments have shown that both the second and third mechanisms rely on cerebellar modulation of thalamic activity for effective somatomotor integration. In the lessobvious case of cortico-cortical communication between vS1 and vM1, synchronous rhythms between structures that promote this form of communication require an intact cerebellum (Popa et al, 2013;Lindeman et al, 2021). Using various methods to inhibit the cerebellar nuclei, it has been shown that cerebellar inactivation reduces the firing rate in motor thalamic neurons (Popa et al, 2013), decreases gamma-rhythmic coherence between vS1 and vM1 (Popa et al, 2013;Lindeman et al, 2021), and impairs the ability of animal to adapt whisking strategies appropriately in a changing sensory context (Proville et al, 2014).…”