Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition

Vladimir Pogorelov; Meiyu Xu; Haleigh R Smith; Gordon F Buchanan; Christopher Pittenger

doi:10.1016/j.expneurol.2015.01.001

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Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition

Journal article

Peer reviewed

Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition

Vladimir Pogorelov, Meiyu Xu, Haleigh R Smith, Gordon F Buchanan and Christopher Pittenger

Experimental neurology, Vol.265, pp.122-128

03/2015

DOI: 10.1016/j.expneurol.2015.01.001

PMCID: PMC4361636

PMID: 25597650

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https://www.ncbi.nlm.nih.gov/pmc/articles/4361636View

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Abstract

The pathophysiology of the tics that define Gilles de la Tourette syndrome (TS) is not well understood. Local disinhibition within the striatum has been hypothesized to play a pathogenic role. In support of this, experimental disinhibition by local antagonism of GABA-A receptors within the striatum produces tic-like phenomenology in monkey and rat. We replicated this effect in mice via local picrotoxin infusion into the dorsal striatum. Infusion of picrotoxin into sensorimotor cortex produced similar movements, accompanied by signs of behavioral activation; higher-dose picrotoxin in the cortex produced seizures. Striatal inhibition with local muscimol completely abolished tic-like movements after either striatal or cortical picrotoxin, confirming their dependence on the striatal circuitry; in contrast, cortical muscimol attenuated but did not abolish movements produced by striatal picrotoxin. Striatal glutamate blockade eliminated tic-like movements after striatal picrotoxin, indicating that glutamatergic afferents are critical for their generation. These studies replicate and extend previous work in monkey and rat, providing additional validation for the local disinhibition model of tic generation. Our results reveal a key role for corticostriatal glutamatergic afferents in the generation of tic-like movements in this model. •Disinhibition in the striatum produces contralateral tic-like movements in mice.•Similar movements are produced by local disinhibition in sensorimotor cortex.•Cortico-striatal interactions are required for these tic-like movements.

Animal model

Basal ganglia

Tourette syndrome

Movement disorders

Tic

Details

Title: Subtitle: Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition
Creators: Vladimir Pogorelov - Department of Psychiatry, Yale University School of Medicine, USA
Meiyu Xu - Department of Psychiatry, Yale University School of Medicine, USA
Haleigh R Smith - Department of Neurology, Yale University School of Medicine, USA
Gordon F Buchanan - Department of Neurology, Yale University School of Medicine, USA
Christopher Pittenger - Department of Psychiatry, Yale University School of Medicine, USA
Resource Type: Journal article
Publication Details: Experimental neurology, Vol.265, pp.122-128
DOI: 10.1016/j.expneurol.2015.01.001
PMID: 25597650
PMCID: PMC4361636
NLM abbreviation: Exp Neurol
ISSN: 0014-4886
eISSN: 1090-2430
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100012135, name: Alison Family Foundation (CP), award: R01MH091861 (CP); DOI: 10.13039/100004823, name: State of Connecticut
Language: English
Date published: 03/2015
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020643202771

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