Homologous organization of cerebellar pathways to sensory, motor, and associative forebrain
Thomas J. Pisano,
Zahra M. Dhanerawala,
Mikhail Kislin,
Dariya Bakshinskaya,
Esteban A. Engel,
Ethan J. Hansen,
Austin T. Hoag,
Junuk Lee,
Nina L. de Oude,
Kannan Umadevi Venkataraju,
Jessica L. Verpeut,
Freek E. Hoebeek,
Ben D. Richardson,
Henk-Jan Boele,
Samuel S.-H. Wang
Affiliations
Thomas J. Pisano
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Zahra M. Dhanerawala
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Mikhail Kislin
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Dariya Bakshinskaya
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Esteban A. Engel
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Ethan J. Hansen
WWAMI Medical Education, University of Idaho, Moscow, ID 83844, USA
Austin T. Hoag
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Junuk Lee
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Nina L. de Oude
Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, the Netherlands
Kannan Umadevi Venkataraju
Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA
Jessica L. Verpeut
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA
Freek E. Hoebeek
Department for Developmental Origins of Disease, Brain Center and Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
Ben D. Richardson
WWAMI Medical Education, University of Idaho, Moscow, ID 83844, USA; Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
Henk-Jan Boele
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA; Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, the Netherlands; Corresponding author
Samuel S.-H. Wang
Neuroscience Institute, Washington Road, Princeton University, Princeton, NJ 08544, USA; Corresponding author
Summary: 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.
