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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

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

doi

10.1038/s41593-017-0004-1

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

1744-1751

issue

12

eissn

1097-6256

issn

1546-1726

pii

10.1038/s41593-017-0004-1

journal_volume

20

pub_type

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