Cerebellar contributions to a brainwide network for flexible behavior in mice

Jessica L. Verpeut, Silke Bergeler, Mikhail Kislin, F. William Townes, Ugne Klibaite, Zahra M. Dhanerawala, Austin Hoag, Sanjeev Janarthanan, Caroline Jung, Junuk Lee, Thomas J. Pisano, Kelly M. Seagraves, Joshua W. Shaevitz, Samuel S.H. Wang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The cerebellum regulates nonmotor behavior, but the routes of influence are not well characterized. Here we report a necessary role for the posterior cerebellum in guiding a reversal learning task through a network of diencephalic and neocortical structures, and in flexibility of free behavior. After chemogenetic inhibition of lobule VI vermis or hemispheric crus I Purkinje cells, mice could learn a water Y-maze but were impaired in ability to reverse their initial choice. To map targets of perturbation, we imaged c-Fos activation in cleared whole brains using light-sheet microscopy. Reversal learning activated diencephalic and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (including thalamus and habenula) and crus I (including hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. To identify functional networks, we used correlated variation in c-Fos activation within each group. Lobule VI inactivation weakened within-thalamus correlations, while crus I inactivation divided neocortical activity into sensorimotor and associative subnetworks. In both groups, high-throughput automated analysis of whole-body movement revealed deficiencies in across-day behavioral habituation to an open-field environment. Taken together, these experiments reveal brainwide systems for cerebellar influence that affect multiple flexible responses.

Original languageEnglish (US)
Article number605
JournalCommunications Biology
Volume6
Issue number1
DOIs
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Medicine (miscellaneous)

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