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 Hoebeek, Ben D. Richardson, Henk Jan Boele*, Samuel S.H. Wang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number109721
JournalCell Reports
Issue number12
Publication statusPublished - 21 Sept 2021

Bibliographical note

We thank Aleksandra Badura for advice on experimental design; Lynn Enquist for discussion and PRV-Bartha 152 (CNNV, P40 OD010996); James Gornet for neural network implementation assistance; Nicolas Renier and Kelly Seagraves for tissue-clearing optimization; Stephan Thiberge for microscopy help; Shruthi Deivasigamani, Joseph Gotto, Joyce Lee, Laura Lynch, Caroline Jung, Sanjeev Janarthanan, Dafina Pacuku, Federico Uquillas, and Thaddeus Weigel for technical assistance; and Pavel Osten for project advice. This work was supported by NIH R01 NS045193 , R01 MH115750 , and U19 NS104648 (S.S.-H.W.), F31 NS089303 (T.J.P.), P40 OD010996 (E.A.E.), R21 DC018365 (B.D.R.), and P20GM103408 (E.J.H. and B.D.R.); Netherlands Organization for Scientific Research Veni ZonMW , 91618112 (H.-J.B.); Erasmus MC Fellowship 106958 (H.-J.B.); New Jersey Autism Center of Excellence (CAUT20AFP006) (H.-J.B.); and the New Jersey Council on Brain Injury Research (J.L.V.).

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