Abstract
Cerebellar outputs take multisynaptic paths to reach higher brain areas, impeding tracing efforts. Here we quantify pathways between cerebellum and contralateral thalamic/corticostriatal structures using the anterograde transsynaptic tracer herpes simplex virus type 1 (H129), the retrograde tracer pseudorabies virus (Bartha), adeno-associated virus, and a whole-brain pipeline for neuron-level analysis using light-sheet microscopy. In ascending pathways, sensorimotor regions contained the most labeled neurons, but higher densities were found in associative areas, including orbital, anterior cingulate, prelimbic, and infralimbic cortex. Ascending paths passed through most thalamic nuclei, especially ventral posteromedial and lateral posterior (sensorimotor), mediodorsal (associative), and reticular (modulatory) nuclei. Retrograde tracing revealed descending paths originating largely from somatomotor 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 functional networks linking cerebellum to forebrain and suggest that cerebellum uses sensory-motor information to guide both movement and nonmotor functions.
