TY - JOUR
T1 - Cerebellar contributions to a brainwide network for flexible behavior in mice
AU - Verpeut, Jessica L.
AU - Bergeler, Silke
AU - Kislin, Mikhail
AU - William Townes, F.
AU - Klibaite, Ugne
AU - Dhanerawala, Zahra M.
AU - Hoag, Austin
AU - Janarthanan, Sanjeev
AU - Jung, Caroline
AU - Lee, Junuk
AU - Pisano, Thomas J.
AU - Seagraves, Kelly M.
AU - Shaevitz, Joshua W.
AU - Wang, Samuel S.H.
N1 - Funding Information:
We thank Henk-Jan Boele, Ben Deverett, Esteban Engel, Laura Lynch, Christina Matl, Dafina Pacuku, Tiffany Pham, and Fred Uquillas for collaboration and discussion, Greg Horwitz for the L7 plasmid, and Archit Verma and Barbara Engelhardt for discussions on statistical testing. This work was supported by NIH R01 RS045193 and R01 MH115750 (S.W.) and the New Jersey Brain Injury Research Council (J.V.).
Funding Information:
We thank Henk-Jan Boele, Ben Deverett, Esteban Engel, Laura Lynch, Christina Matl, Dafina Pacuku, Tiffany Pham, and Fred Uquillas for collaboration and discussion, Greg Horwitz for the L7 plasmid, and Archit Verma and Barbara Engelhardt for discussions on statistical testing. This work was supported by NIH R01 RS045193 and R01 MH115750 (S.W.) and the New Jersey Brain Injury Research Council (J.V.).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-023-04920-0
DO - 10.1038/s42003-023-04920-0
M3 - Article
C2 - 37277453
AN - SCOPUS:85160984160
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 605
ER -