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Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.
Kelly, Elyza; Meng, Fantao; Fujita, Hirofumi; Morgado, Felipe; Kazemi, Yasaman; Rice, Laura C; Ren, Chongyu; Escamilla, Christine Ochoa; Gibson, Jennifer M; Sajadi, Sanaz; Pendry, Robert J; Tan, Tommy; Ellegood, Jacob; Basson, M Albert; Blakely, Randy D; Dindot, Scott V; Golzio, Christelle; Hahn, Maureen K; Katsanis, Nicholas; Robins, Diane M; Silverman, Jill L; Singh, Karun K; Wevrick, Rachel; Taylor, Margot J; Hammill, Christopher; Anagnostou, Evdokia; Pfeiffer, Brad E; Stoodley, Catherine J; Lerch, Jason P; du Lac, Sascha; Tsai, Peter T.
Afiliação
  • Kelly E; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Meng F; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Fujita H; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Morgado F; Departments of Otolaryngology-Head and Neck Surgery, Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kazemi Y; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Rice LC; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada.
  • Ren C; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Escamilla CO; Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC, USA.
  • Gibson JM; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Sajadi S; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Pendry RJ; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Tan T; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Ellegood J; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Basson MA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Blakely RD; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Dindot SV; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada.
  • Golzio C; Centre for Craniofacial and Regenerative Biology and MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
  • Hahn MK; Department of Biomedical Science, Charles E. Schmidt College of Medicine and Brain Institute, Florida Atlantic University, Jupiter, Florida, USA.
  • Katsanis N; Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
  • Robins DM; Institut de Génétique et de Biologie Moléculaire et Cellulaire; Centre National de la Recherche Scientifique; Institut National de la Santé et de la Recherche Médicale; Université de Strasbourg, Illkirch, France.
  • Silverman JL; Department of Biomedical Science, Charles E. Schmidt College of Medicine and Brain Institute, Florida Atlantic University, Jupiter, Florida, USA.
  • Singh KK; ACT-GeM, Department of Human Genetics at Stanley Manne Children's Research Institute; Department of Pediatrics and Cellular and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Wevrick R; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Taylor MJ; MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA, USA.
  • Hammill C; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • Anagnostou E; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
  • Pfeiffer BE; Department of Medical Imaging and Psychology, University of Toronto; Diagnostic Imaging, Hospital for Sick Children, Toronto, ON, USA.
  • Stoodley CJ; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada.
  • Lerch JP; Department of Pediatrics, University of Toronto, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, USA.
  • du Lac S; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Tsai PT; Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC, USA.
Nat Neurosci ; 23(9): 1102-1110, 2020 09.
Article em En | MEDLINE | ID: mdl-32661395
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cerebelo / Córtex Pré-Frontal / Transtorno do Espectro Autista / Vias Neurais Limite: Animals Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cerebelo / Córtex Pré-Frontal / Transtorno do Espectro Autista / Vias Neurais Limite: Animals Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos