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Disruption of KCC2 in Parvalbumin-Positive Interneurons Is Associated With a Decreased Seizure Threshold and a Progressive Loss of Parvalbumin-Positive Interneurons.
- Source :
-
Frontiers in molecular neuroscience [Front Mol Neurosci] 2022 Feb 03; Vol. 14, pp. 807090. Date of Electronic Publication: 2022 Feb 03 (Print Publication: 2021). - Publication Year :
- 2022
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Abstract
- GABA <subscript>A</subscript> receptors are ligand-gated ion channels, which are predominantly permeable for chloride. The neuronal K-Cl cotransporter KCC2 lowers the intraneuronal chloride concentration and thus plays an important role for GABA signaling. KCC2 loss-of-function is associated with seizures and epilepsy. Here, we show that KCC2 is expressed in the majority of parvalbumin-positive interneurons (PV-INs) of the mouse brain. PV-INs receive excitatory input from principle cells and in turn control principle cell activity by perisomatic inhibition and inhibitory input from other interneurons. Upon Cre-mediated disruption of KCC2 in mice, the polarity of the GABA response of PV-INs changed from hyperpolarization to depolarization for the majority of PV-INs. Reduced excitatory postsynaptic potential-spike (E-S) coupling and increased spontaneous inhibitory postsynaptic current (sIPSC) frequencies further suggest that PV-INs are disinhibited upon disruption of KCC2. In vivo , PV-IN-specific KCC2 knockout mice display a reduced seizure threshold and develop spontaneous sometimes fatal seizures. We further found a time dependent loss of PV-INs, which was preceded by an up-regulation of pro-apoptotic genes upon disruption of KCC2.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Herrmann, Gerth, Dittmann, Pensold, Ungelenk, Liebmann and Hübner.)
Details
- Language :
- English
- ISSN :
- 1662-5099
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Frontiers in molecular neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 35185464
- Full Text :
- https://doi.org/10.3389/fnmol.2021.807090