| First Author | Kerti-Szigeti K | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 31 | Pages | 10219-33 |
| PubMed ID | 25080584 | Mgi Jnum | J:223173 |
| Mgi Id | MGI:5648161 | Doi | 10.1523/JNEUROSCI.1721-14.2014 |
| Citation | Kerti-Szigeti K, et al. (2014) Synaptic GABAA receptor clustering without the gamma2 subunit. J Neurosci 34(31):10219-33 |
| abstractText | Rapid activation of postsynaptic GABAA receptors (GABAARs) is crucial in many neuronal functions, including the synchronization of neuronal ensembles and controlling the precise timing of action potentials. Although the gamma2 subunit is believed to be essential for the postsynaptic clustering of GABAARs, synaptic currents have been detected in neurons obtained from gamma2(-/-) mice. To determine the role of the gamma2 subunit in synaptic GABAAR enrichment, we performed a spatially and temporally controlled gamma2 subunit deletion by injecting Cre-expressing viral vectors into the neocortex of GABAARgamma2(77I)lox mice. Whole-cell recordings revealed the presence of miniature IPSCs in Cre(+) layer 2/3 pyramidal cells (PCs) with unchanged amplitudes and rise times, but significantly prolonged decays. Such slowly decaying currents could be evoked in PCs by action potentials in presynaptic fast-spiking interneurons. Freeze-fracture replica immunogold labeling revealed the presence of the alpha1 and beta3 subunits in perisomatic synapses of cells that lack the gamma2 subunit. Miniature IPSCs in Cre(+) PCs were insensitive to low concentrations of flurazepam, providing a pharmacological confirmation of the lack of the gamma2 subunit. Receptors assembled from only alphabeta subunits were unlikely because Zn(2+) did not block the synaptic currents. Pharmacological experiments indicated that the alphabetagamma3 receptor, rather than the alphabetadelta, alphabetaepsilon, or alphabetagamma1 receptors, was responsible for the slowly decaying IPSCs. Our data demonstrate the presence of IPSCs and the synaptic enrichment of the alpha1 and beta3 subunits and suggest that the gamma3 subunit is the most likely candidate for clustering GABAARs at synapses in the absence of the gamma2 subunit. |
