Dataset Information

Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.

ABSTRACT: 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.

SUBMITTER: Kelly E

PROVIDER: S-EPMC7483861 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.

Kelly Elyza E Meng Fantao F Fujita Hirofumi H Morgado Felipe F Kazemi Yasaman Y Rice Laura C LC Ren Chongyu C Escamilla Christine Ochoa CO Gibson Jennifer M JM Sajadi Sanaz S Pendry Robert J RJ Tan Tommy T Ellegood Jacob J Basson M Albert MA Blakely Randy D RD Dindot Scott V SV Golzio Christelle C Hahn Maureen K MK Katsanis Nicholas N Robins Diane M DM Silverman Jill L JL Singh Karun K KK Wevrick Rachel R Taylor Margot J MJ Hammill Christopher C Anagnostou Evdokia E Pfeiffer Brad E BE Stoodley Catherine J CJ Lerch Jason P JP du Lac Sascha S Tsai Peter T PT

Nature neuroscience 20200713 9

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-lin ...[more]

PMID: 32661395

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Dataset Information

Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.

Publications

Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.

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