Parallel Organization of Cerebellar Pathways to Sensory, Motor, and Associative Forebrain

Abstract

Cerebellar outputs take polysynaptic routes to reach the rest of the brain, impeding conventional tracing efforts. Here we quantify pathways between cerebellar cortex and thalamus, striatum, and neocortex using anterograde and retrograde transsynaptic tracing viruses combined with a novel whole-brain pipeline for quantitative neuron-level analysis using light-sheet microscopy. Retrograde tracing found a majority of descending paths originating from somatomotor cortex, validating the pipeline. Ascending paths encompassed most thalamic nuclei, especially ventral posteromedial and lateral posterior (sensorimotor), mediodorsal (associative), and reticular (modulatory) nuclei. For cerebellar output to neocortex, sensorimotor regions contained the most total labeled neurons, but higher projection densities were found in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Patterns of ascending influence correlated with anatomical pathway strengths as measured by brainwide mapping of c-Fos responses to optogenetic inhibition of Purkinje cells. Our results reveal parallel anatomical networks linking single areas of cerebellar cortex to diverse forebrain forebrain targets. We suggest that shared areas of cerebellum are capable of using sensory-motor information to guide both movement and nonmotor functions.