Decoding state-dependent cortical-cerebellar cellular functional connectivity in the mouse brain

The cortex and cerebellum form multi-synaptic reciprocal connections. We investigate the functional connectivity between single spiking cerebellar neurons and the population activity of the mouse dorsal cortex using mesoscale imaging. Cortical representations of individual cerebellar neurons vary significantly across different brain states but are drawn from a common set of cortical networks. These cortical-cerebellar connectivity features are observed in mossy fibers and Purkinje cells as well as neurons in different cerebellar lobules, albeit with variations across cell types and regions. Complex spikes of Purkinje cells preferably associate with the sensorimotor cortex, whereas simple spikes display more diverse cortical connectivity patterns. The spontaneous functional connectivity patterns align with cerebellar neurons’ functional responses to external stimuli in a modality-specific manner. The tuning properties of subsets of cerebellar neurons differ between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns with mesoscale cortical activity.