@article{4fd93f407bc442ee966a3a5b24e3f3f8,
title = "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.",
author = "Elyza Kelly and Fantao Meng and Hirofumi Fujita and Felipe Morgado and Yasaman Kazemi and Rice, {Laura C.} and Chongyu Ren and Escamilla, {Christine Ochoa} and Gibson, {Jennifer M.} and Sanaz Sajadi and Pendry, {Robert J.} and Tommy Tan and Jacob Ellegood and {Albert Basson}, M. and Blakely, {Randy D.} and Dindot, {Scott V.} and Christelle Golzio and Hahn, {Maureen K.} and Nicholas Katsanis and Robins, {Diane M.} and Silverman, {Jill L.} and Singh, {Karun K.} and Rachel Wevrick and Taylor, {Margot J.} and Christopher Hammill and Evdokia Anagnostou and Pfeiffer, {Brad E.} and Stoodley, {Catherine J.} and Lerch, {Jason P.} and {du Lac}, Sascha and Tsai, {Peter T.}",
note = "Funding Information: P.T.T. acknowledges support from the National Institute of Neurologic Disorders and Stroke (NS083733), the National Institute of Mental Health (MH116882), the Tuberous Sclerosis Alliance and the Department of Defense. E.K. acknowledges support from National Institute of Neurologic Disorders and Stroke (NS107004) and Autism Speaks. H.F. and S.d.L. acknowledge support from the National Institute of Neurologic Disorders and Stroke (NS095232 and NS105039). F. Morgado, J.E. and J.P.L. acknowledge support from the Canadian Institute for Health Research and the Ontario Brain Institute. L.C.R and C.J.S. acknowledge support from the National Institute for Health (MH106957). M.A.B. acknowledges support from the Medical Research Council (MR/K022377/1). N.K. acknowledges support from the National Institute of Mental Health (MH094268) and declares that he is a paid consultant for Rescindo Therapeutics, although this does not provide a competing interest with this study. P.T.T. and E.K. acknowledge support from V. Jakkamsetti and J. Pascual for support with in vivo extracellular and acute slice recordings recordings and analysis; S. Birnbaum for assistance in behavioral studies; G. Konopka, C. Powell, L. Osburne, J. Foster, J. Lai, K. Rilett, E. Kim and A. Raznahan for generous provision of animal models; and J. Chadwick for graphics assistance. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = sep,
day = "1",
doi = "10.1038/s41593-020-0665-z",
language = "English (US)",
volume = "23",
pages = "1102--1110",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "9",
}