Decoding State-Dependent Cortical-Cerebellar Cellular Functional Connectivity in the Mouse Brain

Abstract

ABSTRACTThe cerebellum participates in motor tasks, but also a broad spectrum of cognitive functions. However, cerebellar connections with higher areas such as cortex are not direct and the mechanisms by which the cerebellum integrates and processes diverse information streams are not clear. We investigated the functional connectivity between single cerebellar neurons and population activity of the dorsal cortex using mesoscale imaging. Our findings revealed dynamic coupling between individual cerebellar neurons and diverse cortical networks, and such functional association can be influenced by local excitatory and inhibitory connections. While the cortical representations of individual cerebellar neurons displayed marked changes across different brain states, the overall assignments to specific cortical topographic areas at the population level remained stable. Simple spikes and complex spikes of the same Purkinje cells displayed either similar or distinct cortical functional connectivity patterns. Moreover, the spontaneous functional connectivity patterns aligned with cerebellar neurons’ functional responses to external stimuli in a modality-specific manner. Importantly, the tuning properties of subsets of cerebellar neurons differed between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns. Collectively, our results provide a comprehensive view of the state-dependent cortical-cerebellar functional connectivity landscape and demonstrate that remapping of long-range functional network association could underlie state-dependent change in sensory processing.