The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders
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 diffe...
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doaj-f75281fe53ee452c868a39ecd100241e2020-11-24T21:27:24ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2015-09-01910.3389/fnins.2015.00296156522The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disordersMatthew W Mosconi0Matthew W Mosconi1Zheng eWang2Lauren M Schmitt3Peter eTsai4John A Sweeney5University of KansasUniversity of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterUniversity of Texas Southwestern Medical CenterThe 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.http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00296/fullCerebellumGaitPostureAutism Spectrum Disordersensorimotoroculomotor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew W Mosconi Matthew W Mosconi Zheng eWang Lauren M Schmitt Peter eTsai John A Sweeney |
spellingShingle |
Matthew W Mosconi Matthew W Mosconi Zheng eWang Lauren M Schmitt Peter eTsai John A Sweeney The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders Frontiers in Neuroscience Cerebellum Gait Posture Autism Spectrum Disorder sensorimotor oculomotor |
author_facet |
Matthew W Mosconi Matthew W Mosconi Zheng eWang Lauren M Schmitt Peter eTsai John A Sweeney |
author_sort |
Matthew W Mosconi |
title |
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
title_short |
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
title_full |
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
title_fullStr |
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
title_full_unstemmed |
The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
title_sort |
role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2015-09-01 |
description |
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. |
topic |
Cerebellum Gait Posture Autism Spectrum Disorder sensorimotor oculomotor |
url |
http://journal.frontiersin.org/Journal/10.3389/fnins.2015.00296/full |
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