Open AccessRegulation of autism-relevant behaviors by cerebellar–prefrontal cortical circuits
Author(s) -
Elyza Kelly,
Fantao Meng,
Hirofumi Fujita,
Felipe Morgado,
Yasaman Kazemi,
Laura C. Rice,
Cheng Ren,
Christine Ochoa Escamilla,
Jennifer M. Gibson,
Sanaz Sajadi,
Robert J. Pendry,
T. S. H. Tan,
Jacob Ellegood,
M. Albert Basson,
Randy D. Blakely,
Scott V. Dindot,
Christelle Golzio,
Maureen K. Hahn,
Nicholas Katsanis,
Diane M. Robins,
Jill L. Silverman,
Karun K. Singh,
Rachel Wevrick,
Margot J. Taylor,
Christopher Hammill,
Evdokia Anagnostou,
Brad E. Pfeiffer,
Catherine J. Stoodley,
Jason P. Lerch,
Sascha du,
Peter T. Tsai
Publication year - 2020
Publication title -
nature neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.403
H-Index - 422
eISSN - 1546-1726
pISSN - 1097-6256
DOI - 10.1038/s41593-020-0665-z
Subject(s) - neuroscience , cerebellum , prefrontal cortex , autism , psychology , cerebellar vermis , thalamus , biological neural network , cognition , developmental psychology
Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.