@article{462377c0f2a34dcd87707795b6f6528e,
title = "A Critical Period for Development of Cerebellar-Mediated Autism-Relevant Social Behavior",
abstract = "The cerebellum has been increasingly implicated in autism spectrum disorder (ASD) with many ASD-linked genes impacting both cerebellar function and development. However, the precise timing and critical periods of when abnormal cerebellar neurodevelopment contributes to ASD-relevant behaviors remains poorly understood. In this study, we identify a critical period for the development of ASD-relevant behaviors in a cerebellar male mouse model of tuberous sclerosis complex (TSC), by using the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin, to pharmacologically inhibit dysregulated downstream signaling. We find independent critical periods during which abnormal ASD-relevant behaviors develop for the two core ASD diagnostic criteria, social impairments and behavioral flexibility, and delineate an anatomic, physiological, and behavioral framework. These findings not only further our understanding of the genetic mechanisms underlying the timing of ASD-relevant behaviors but also have the capacity to inform potential therapies to optimize treatment interventions.",
keywords = "Purkinje cell, autism, cerebellum, critical period, tuberous sclerosis",
author = "Gibson, {Jennifer M.} and Howland, {Cleone P.} and Chongyu Ren and Cyrena Howland and Alexandra Vernino and Tsai, {Peter T.}",
note = "Funding Information: Acknowledgements: We thank the University of Texas Southwestern Medical Center Whole Brain Microscopy Core Facility, RRID:SCR_017949, for assistance with microscopy and imaging. We also thank the University of Texas Southwestern Medical Center Behavioral Phenotyping Core. J.M.G. was supported by the National Heart, Lung, and Blood Institute Grant 1T32HL139438-01A1. P.T.T. was supported by the National Institute of Neurologic Disorders and Stroke of the National Institutes of Health (NIH) Grant K08 NS083733 and National Institute of Mental Health of the NIH Grant R01 MH116882. The authors declare no competing financial interests. Correspondence should be addressed to Peter T. Tsai at peter.tsai@utsouthwestern.edu. https://doi.org/10.1523/JNEUROSCI.1230-21.2021 Copyright {\textcopyright} 2022 the authors Funding Information: We thank the University of Texas Southwestern Medical Center Whole Brain Microscopy Core Facility, RRID:SCR_017949, for assistance with microscopy and imaging. We also thank the University of Texas Southwestern Medical Center Behavioral Phenotyping Core. J.M.G. was supported by the National Heart, Lung, and Blood Institute Grant 1T32HL139438-01A1. P.T.T. was supported by the National Institute of Neurologic Disorders and Stroke of the National Institutes of Health (NIH) Grant K08 NS083733 and National Institute of Mental Health of the NIH Grant R01 MH116882. Publisher Copyright: Copyright {\textcopyright} 2022 the authors",
year = "2022",
month = mar,
day = "30",
doi = "10.1523/JNEUROSCI.1230-21.2021",
language = "English (US)",
volume = "42",
pages = "2804--2823",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "13",
}