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.

Automated summary

The study used transsynaptic tracing techniques to quantify pathways between the cerebellum and forebrain, revealing the involvement of most thalamic nuclei and cortical regions in these pathways, especially associative areas. Homologous networks connecting single areas of the cerebellar cortex to diverse forebrain targets were identified, with shared cerebellar areas positioned to provide sensory-motor information to regions implicated in both movement and nonmotor function.