Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice

Catherine J. Stoodley, Anila M. D'Mello, Jacob Ellegood, Vikram Jakkamsetti, Pei Liu, Mary Beth Nebel, Jennifer M. Gibson, Elyza Kelly, Fantao Meng, Christopher A. Cano, Juan M. Pascual, Stewart H. Mostofsky, Jason P. Lerch, Peter T. Tsai

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

Original languageEnglish (US)
Pages (from-to)1744-1751
Number of pages8
JournalNature Neuroscience
Volume20
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Autistic Disorder
Purkinje Cells
Parietal Lobe
Autism Spectrum Disorder
Social Behavior

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. / Stoodley, Catherine J.; D'Mello, Anila M.; Ellegood, Jacob; Jakkamsetti, Vikram; Liu, Pei; Nebel, Mary Beth; Gibson, Jennifer M.; Kelly, Elyza; Meng, Fantao; Cano, Christopher A.; Pascual, Juan M.; Mostofsky, Stewart H.; Lerch, Jason P.; Tsai, Peter T.

In: Nature Neuroscience, Vol. 20, No. 12, 01.12.2017, p. 1744-1751.

Research output: Contribution to journalArticle

Stoodley, CJ, D'Mello, AM, Ellegood, J, Jakkamsetti, V, Liu, P, Nebel, MB, Gibson, JM, Kelly, E, Meng, F, Cano, CA, Pascual, JM, Mostofsky, SH, Lerch, JP & Tsai, PT 2017, 'Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice', Nature Neuroscience, vol. 20, no. 12, pp. 1744-1751. https://doi.org/10.1038/s41593-017-0004-1
Stoodley, Catherine J. ; D'Mello, Anila M. ; Ellegood, Jacob ; Jakkamsetti, Vikram ; Liu, Pei ; Nebel, Mary Beth ; Gibson, Jennifer M. ; Kelly, Elyza ; Meng, Fantao ; Cano, Christopher A. ; Pascual, Juan M. ; Mostofsky, Stewart H. ; Lerch, Jason P. ; Tsai, Peter T. / Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. In: Nature Neuroscience. 2017 ; Vol. 20, No. 12. pp. 1744-1751.
@article{4ac651a12a14490cb3075833553da458,
title = "Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice",
abstract = "Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.",
author = "Stoodley, {Catherine J.} and D'Mello, {Anila M.} and Jacob Ellegood and Vikram Jakkamsetti and Pei Liu and Nebel, {Mary Beth} and Gibson, {Jennifer M.} and Elyza Kelly and Fantao Meng and Cano, {Christopher A.} and Pascual, {Juan M.} and Mostofsky, {Stewart H.} and Lerch, {Jason P.} and Tsai, {Peter T.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41593-017-0004-1",
language = "English (US)",
volume = "20",
pages = "1744--1751",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice

AU - Stoodley, Catherine J.

AU - D'Mello, Anila M.

AU - Ellegood, Jacob

AU - Jakkamsetti, Vikram

AU - Liu, Pei

AU - Nebel, Mary Beth

AU - Gibson, Jennifer M.

AU - Kelly, Elyza

AU - Meng, Fantao

AU - Cano, Christopher A.

AU - Pascual, Juan M.

AU - Mostofsky, Stewart H.

AU - Lerch, Jason P.

AU - Tsai, Peter T.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

AB - Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI-inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

UR - http://www.scopus.com/inward/record.url?scp=85035320449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035320449&partnerID=8YFLogxK

U2 - 10.1038/s41593-017-0004-1

DO - 10.1038/s41593-017-0004-1

M3 - Article

VL - 20

SP - 1744

EP - 1751

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 12

ER -