| First Author | Nani F | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 31 | Pages | 12718-27 |
| PubMed ID | 23904608 | Mgi Jnum | J:199871 |
| Mgi Id | MGI:5505719 | Doi | 10.1523/JNEUROSCI.0388-13.2013 |
| Citation | Nani F, et al. (2013) Tyrosine Phosphorylation of GABAA Receptor gamma2-Subunit Regulates Tonic and Phasic Inhibition in the Thalamus. J Neurosci 33(31):12718-27 |
| abstractText | 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 gamma2-subunits. As phosphorylation of gamma2 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 gamma2(Y365/367F)+/- (HT) animals (homozygotes are not viable in utero), the expression levels of GABAA receptor alpha4-subunits were increased in the thalamus of female, but not male mice. Raised delta-subunit expression levels were also observed in female gamma2(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 delta-subunit superagonist THIP, and the blocker Zn(2+), were higher in female HT relay cells. This is consistent with upregulation of extrasynaptic GABAA receptors containing alpha4- and delta-subunits to enhance tonic inhibition. In contrast, the sensitivity of GABAA receptors mediating inhibition in the female gamma2(Y356/367F) +/- to neurosteroids was markedly reduced compared with WT. We conclude that disrupting tyrosine phosphorylation of the gamma2-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. |
