Homologous organization of cerebellar pathways to sensory, motor, and associative forebrain

Cerebellar outputs take polysynaptic routes to reach the rest of the brain, impeding conventional tracing. Here, we quantify pathways between the cerebellum and forebrain by using transsynaptic tracing viruses and a whole-brain analysis pipeline. With retrograde tracing, we find that most descending paths originate from the somatomotor cortex. Anterograde tracing of ascending paths encompasses most thalamic nuclei, especially ventral posteromedial, lateral posterior, mediodorsal, and reticular nuclei. In the neocortex, sensorimotor regions contain the most labeled neurons, but we find higher densities in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Patterns of ascending expression correlate with c-Fos expression after optogenetic inhibition of Purkinje cells. Our results reveal homologous networks linking single areas of the cerebellar cortex to diverse forebrain targets. We conclude that shared areas of the cerebellum are positioned to provide sensory-motor information to regions implicated in both movement and nonmotor function. [Display omitted] •BrainPipe is a pipeline for automated whole-brain analysis of light-sheet microscopy•Whole-brain quantification reveals dense cerebellar ascending paths to frontal areas•Cerebellar paths to reticular thalamic nucleus provide a substantial modulatory path•Single regions of cerebellar cortex connect with diverse neocortical areas Pisano et al. use transsynaptic tracing and whole-brain light-sheet microscopy to quantitatively map cerebellar paths to and from the forebrain, including relatively dense projections to the prefrontal neocortex. Divergence of paths from single injection sites suggests that a single cerebellar region can influence multiple thalamic and neocortical targets at once.