TY - JOUR T1 - Cerebellar contributions to a brainwide network for flexible behavior JF - bioRxiv DO - 10.1101/2021.12.07.471685 SP - 2021.12.07.471685 AU - Jessica L. Verpeut AU - Silke Bergeler AU - Mikhail Kislin AU - F. William Townes AU - Ugne Klibaite AU - Zahra M. Dhanerawala AU - Austin Hoag AU - Caroline Jung AU - Junuk Lee AU - Thomas J. Pisano AU - Kelly M. Seagraves AU - Joshua W. Shaevitz AU - Samuel S.-H. Wang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/12/08/2021.12.07.471685.abstract N2 - The cerebellum regulates nonmotor behavior, but the routes by which it exerts its influence are not well characterized. Here we report a necessary role for posterior cerebellum in guiding flexible behavior, acting through a network of diencephalic and neocortical structures. After chemogenetic inhibition of Purkinje cells in lobule VI or crus I, high-throughput automated analysis of complex whole-body movement revealed deficiencies in adaptation across days to an open field environment. Neither perturbation affected gait, within-day open-field adaptation, or location preference. In a Y-maze task, mice could learn but were impaired in their 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 regions and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (thalamus and habenula) and crus I (hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. Taken together, these experiments reveal parts of a brainwide system for cerebellar influence to guide flexible learning.Competing Interest StatementThe authors have declared no competing interest. ER -