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• W2078082157 abstract "GABA-mediated tonic and phasic inhibition of thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) was studied after ablating tyrosine (Y) phosphorylation of receptor γ2-subunits. As phosphorylation of γ2 Y365 and Y367 reduces receptor internalization, to understand their importance for inhibition we created a knock-in mouse in which these residues are replaced by phenylalanines. On comparing wild-type (WT) and γ2^Y365/367F+/− (HT) animals (homozygotes are not viable <i>in utero</i>), the expression levels of GABA_A receptor α4-subunits were increased in the thalamus of female, but not male mice. Raised δ-subunit expression levels were also observed in female γ2^Y365/367F +/− thalamus. Electrophysiological analyses revealed no difference in the level of inhibition in male WT and HT dLGN, while both the spontaneous inhibitory postsynaptic activity and the tonic current were significantly augmented in female HT relay cells. The sensitivity of tonic currents to the δ-subunit superagonist THIP, and the blocker Zn²⁺, were higher in female HT relay cells. This is consistent with upregulation of extrasynaptic GABA_A receptors containing α4- and δ-subunits to enhance tonic inhibition. In contrast, the sensitivity of GABA_A receptors mediating inhibition in the female γ2^Y356/367F +/− to neurosteroids was markedly reduced compared with WT. We conclude that disrupting tyrosine phosphorylation of the γ2-subunit activates a sex-specific increase in tonic inhibition, and this most likely reflects a genomic-based compensation mechanism for the reduced neurosteroid sensitivity of inhibition measured in female HT relay neurons." @default.
• W2078082157 created "2016-06-24" @default.
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• W2078082157 date "2013-07-31" @default.
• W2078082157 modified "2023-09-25" @default.
• W2078082157 title "Tyrosine Phosphorylation of GABAA Receptor 2-Subunit Regulates Tonic and Phasic Inhibition in the Thalamus" @default.
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• W2078082157 doi "https://doi.org/10.1523/jneurosci.0388-13.2013" @default.
• W2078082157 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4400286" @default.
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