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

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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Pogorelov V,Xu M,Smith HR,Buchanan GF,Pittenger C

doi

10.1016/j.expneurol.2015.01.001

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

122-8

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(15)00003-5

journal_volume

265

pub_type

杂志文章

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