title: The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders.
abstract: The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.
authors.affiliation: Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies, University of Kansas Lawrence, KS, USA ; Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Mosconi
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Schmitt
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA ; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Dallas, TX, USA ; Department of Neuroscience, University of Texas Southwestern Dallas, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tsai
authors.affiliation: Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
keywords: autism spectrum disorder; cerebellum; gait; genetics; oculomotor; pathophysiology; precision grip; sensorimotor