Unknown

Dataset Information

0

GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease.


ABSTRACT: We report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl-]i levels. Dopamine deprivation also dramatically increases CGINs dendritic arbors and monosynaptic interconnections probability, suggesting the formation of a dense CGINs network. The NKCC1 chloride importer antagonist bumetanide, which reduces [Cl-]i levels, restores GABAergic inhibition, the cortico-striatal pause-rebound response, and attenuates motor effects of dopamine deprivation. Therefore, most of the striatal cholinergic excitatory drive is balanced by a concomitant powerful GABAergic inhibition that is impaired by dopamine deprivation. The attenuation by bumetanide of cardinal features of Parkinson's disease paves the way to a novel therapeutic strategy based on a restoration of low [Cl-]i levels and GABAergic inhibition.

SUBMITTER: Lozovaya N 

PROVIDER: S-EPMC5897332 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

altmetric image

Publications

GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease.

Lozovaya N N   Eftekhari S S   Cloarec R R   Gouty-Colomer L A LA   Dufour A A   Riffault B B   Billon-Grand M M   Pons-Bennaceur A A   Oumar N N   Burnashev N N   Ben-Ari Y Y   Hammond C C  

Nature communications 20180412 1


We report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl<sup>-</sup>]<sub>i</sub> levels. Dopamine deprivation also dramat  ...[more]

Similar Datasets

| S-EPMC3245803 | biostudies-literature
| S-EPMC6519226 | biostudies-literature
| S-EPMC9509469 | biostudies-literature
| S-EPMC7854471 | biostudies-literature
| S-EPMC9648160 | biostudies-literature
| S-EPMC2766344 | biostudies-literature
| S-EPMC3976769 | biostudies-literature
| S-EPMC7547109 | biostudies-literature
| S-EPMC6104028 | biostudies-literature
| S-EPMC1572128 | biostudies-literature