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

التفاصيل البيبلوغرافية
العنوان: Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.
المؤلفون: Kelly E; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA., Meng F; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Fujita H; Departments of Otolaryngology-Head and Neck Surgery, Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Morgado F; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada., Kazemi Y; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Rice LC; Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC, USA., Ren C; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Escamilla CO; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Gibson JM; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Neuroscience, 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 Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA., Tan T; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA., Ellegood J; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada., Basson MA; Centre for Craniofacial and Regenerative Biology and MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK., Blakely RD; Department of Biomedical Science, Charles E. Schmidt College of Medicine and Brain Institute, Florida Atlantic University, Jupiter, Florida, USA., Dindot SV; Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA., Golzio C; 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., Hahn MK; Department of Biomedical Science, Charles E. Schmidt College of Medicine and Brain Institute, Florida Atlantic University, Jupiter, Florida, USA., Katsanis N; 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., Robins DM; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA., Silverman JL; MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA, USA., Singh KK; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada., Wevrick R; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada., Taylor MJ; Department of Medical Imaging and Psychology, University of Toronto; Diagnostic Imaging, Hospital for Sick Children, Toronto, ON, USA., Hammill C; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada., Anagnostou E; Department of Pediatrics, University of Toronto, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, USA., Pfeiffer BE; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA., Stoodley CJ; Department of Neuroscience, Center for Behavioral Neuroscience, American University, Washington, DC, USA., Lerch JP; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.; Mouse Imaging Centre, Toronto Hospital for Sick Children, Toronto, ON, Canada.; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK., du Lac S; Departments of Otolaryngology-Head and Neck Surgery, Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Tsai PT; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA. peter.tsai@utsouthwestern.edu.; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA. peter.tsai@utsouthwestern.edu.; Departments of Psychiatry and Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA. peter.tsai@utsouthwestern.edu.
المصدر: Nature neuroscience [Nat Neurosci] 2020 Sep; Vol. 23 (9), pp. 1102-1110. Date of Electronic Publication: 2020 Jul 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 9809671 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1726 (Electronic) Linking ISSN: 10976256 NLM ISO Abbreviation: Nat Neurosci Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: New York, NY : Nature Publishing Group
Original Publication: New York, NY : Nature America Inc., c1998-
مواضيع طبية MeSH: Autism Spectrum Disorder/*physiopathology , Cerebellum/*physiopathology , Neural Pathways/*physiopathology , Prefrontal Cortex/*physiopathology, Animals ; Male ; Mice ; Mice, Mutant Strains
مستخلص: 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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معلومات مُعتمدة: P50 MH094268 United States MH NIMH NIH HHS; MR/K022377/1 United Kingdom MRC_ Medical Research Council; K08 NS083733 United States NS NINDS NIH HHS; F31 NS107004 United States NS NINDS NIH HHS; Canada CIHR; R01 NS105039 United States NS NINDS NIH HHS; R01 NS097808 United States NS NINDS NIH HHS; MR/N026063/1 United Kingdom MRC_ Medical Research Council; R15 MH106957 United States MH NIMH NIH HHS; R21 NS095232 United States NS NINDS NIH HHS; R01 MH116882 United States MH NIMH NIH HHS
تواريخ الأحداث: Date Created: 20200715 Date Completed: 20201130 Latest Revision: 20240329
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7483861
DOI: 10.1038/s41593-020-0665-z
PMID: 32661395
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-1726
DOI:10.1038/s41593-020-0665-z