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Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures.


ABSTRACT: Stroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex ?4?3? are concurrently reduced (?-GABAARs). In vivo and in vitro analyses show that stroke-induced glutamate release activates NMDA receptors, thereby reducing KCC2 transporters and down-regulates ?-GABAARs. Functionally, this is associated with improved motor performance on the RotaRod, a test in which mice are forced to move in a similar manner to rehabilitative training sessions. As an adverse side effect, decreased tonic inhibition facilitates post-stroke epileptic seizures. Our data imply that early and sometimes surprisingly fast recovery following stroke is supported by homeostatic, endogenous plasticity of extrasynaptic GABAA receptors.

SUBMITTER: Jaenisch N 

PROVIDER: S-EPMC4870642 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Reduced tonic inhibition after stroke promotes motor performance and epileptic seizures.

Jaenisch Nadine N   Liebmann Lutz L   Guenther Madlen M   Hübner Christian A CA   Frahm Christiane C   Witte Otto W OW  

Scientific reports 20160518


Stroke survivors often recover from motor deficits, either spontaneously or with the support of rehabilitative training. Since tonic GABAergic inhibition controls network excitability, it may be involved in recovery. Middle cerebral artery occlusion in rodents reduces tonic GABAergic inhibition in the structurally intact motor cortex (M1). Transcript and protein abundance of the extrasynaptic GABAA-receptor complex α4β3δ are concurrently reduced (δ-GABAARs). In vivo and in vitro analyses show th  ...[more]

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