| First Author | Ferando I | Year | 2015 |
| Journal | Neuropharmacology | Volume | 88 |
| Pages | 91-8 | PubMed ID | 25261782 |
| Mgi Jnum | J:358753 | Mgi Id | MGI:6855600 |
| Doi | 10.1016/j.neuropharm.2014.09.010 | Citation | Ferando I, et al. (2015) In vitro gamma oscillations following partial and complete ablation of delta subunit-containing GABAA receptors from parvalbumin interneurons. Neuropharmacology 88:91-8 |
| abstractText | Perisynaptic and extrasynaptic delta subunit-containing GABAA receptors (delta-GABAARs) mediate tonic conductances in many neurons. On principal cells of the neocortex and hippocampus they comprise alpha4 subunits, whereas they usually contain alpha1 on various interneurons. Specific characteristics of delta-GABAARs are their pharmacology and high plasticity. In particular delta-GABAARs are sensitive to low concentrations of neurosteroids (NS) and during times of altered NS production (stress, puberty, ovarian cycle and pregnancy) delta-GABAARs expression varies in many neurons regardless of the alpha subunits they contain, with direct consequences for neuronal excitability and network synchrony. For example delta-GABAARs plasticity on INs underlies modifications in hippocampal gamma oscillations during pregnancy or over the ovarian cycle. Most delta-GABAAR-expressing INs in CA3 stratum pyramidale (SP) are parvalbumin (PV) + INs, whose fundamental role in gamma oscillations generation and control has been extensively investigated. In this study we reduced or deleted delta-subunits in PV + INs, with the use of a PV/Cre-Gabrd/floxed genetic system. We find that in vitro CA3 gamma oscillations of both PV-Gabrd(+/-)and PV-Gabrd(-/-) mice are characterized by higher frequencies than WT controls. The increased frequencies could be lowered to control levels in PV-Gabrd(+/-) by the NS allopregnanolone (3alpha,5alpha-tetrahydroprogesterone, 100 nM) but not the synthetic delta-GABAAR positive allosteric modulator 4-Chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3-yl] benzamide (DS-2, 10 muM). This is consistent with the idea that DS-2, in contrast to ALLO, selectively targets alpha4/delta-GABAARs but not the alpha1/delta-GABAARs found on INs. Therefore, development of drugs selective for IN-specific alpha1/delta-GABAARs may be useful in neurological and psychiatric conditions correlated with altered PV + IN function and aberrant gamma oscillations. |
