Journal articles
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.
Keywords :
Cellular neuroscience
Parkinson's disease
Cited literature [61 references]
https://hal-amu.archives-ouvertes.fr/hal-01963841
Contributor : Fanny Pra <>
Submitted on : Friday, December 21, 2018 - 4:01:06 PM
Last modification on : Thursday, March 11, 2021 - 3:16:27 AM
Long-term archiving on: : Friday, March 22, 2019 - 5:25:13 PM
Contributor : Fanny Pra <>
Submitted on : Friday, December 21, 2018 - 4:01:06 PM
Last modification on : Thursday, March 11, 2021 - 3:16:27 AM
Long-term archiving on: : Friday, March 22, 2019 - 5:25:13 PM
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lozovaya et al 2018.pdf
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