A Critical Period for Development of Cerebellar-Mediated Autism-Relevant Social Behavior

Jennifer M. Gibson, Cleone P. Howland, Chongyu Ren, Cyrena Howland, Alexandra Vernino, Peter T. Tsai

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2804-2823
Number of pages20
JournalJournal of Neuroscience
Issue number13
StatePublished - Mar 30 2022


  • Purkinje cell
  • autism
  • cerebellum
  • critical period
  • tuberous sclerosis

ASJC Scopus subject areas

  • Medicine(all)


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