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Publication : Allopregnanolone Effects on Inhibition in Hippocampal Parvalbumin Interneurons.

First Author  Lu X Year  2023
Journal  eNeuro Volume  10
Issue  3 PubMed ID  36725341
Mgi Jnum  J:335027 Mgi Id  MGI:7446034
Doi  10.1523/ENEURO.0392-22.2023 Citation  Lu X, et al. (2023) Allopregnanolone Effects on Inhibition in Hippocampal Parvalbumin Interneurons. eNeuro 10(3):ENEURO.0392-22.2023
abstractText  Allopregnanolone (AlloP) is a neurosteroid that potentiates ionotropic GABAergic (GABA(A)) inhibition and is approved for treating postpartum depression in women. Although the antidepressant mechanism of AlloP is largely unknown, it could involve selective action at GABA(A) receptors containing the delta subunit. Despite previous evidence for selective effects of AlloP on alpha4/delta-containing receptors of hippocampal dentate granule cells (DGCs), other recent results failed to demonstrate selectivity at these receptors (Lu et al., 2020). In contrast to DGCs, hippocampal fast-spiking parvalbumin (PV) interneurons express an unusual variant partnership of delta subunits with alpha1 subunits. Here, we hypothesized that native alpha1/delta receptors in hippocampal fast-spiking interneurons may provide a preferred substrate for AlloP. Contrary to the hypothesis, electrophysiology from genetically tagged PV interneurons in hippocampal slices from male mice showed that 100 nm AlloP promoted phasic inhibition by increasing the sIPSC decay, but tonic inhibition was not detectably altered. Co-application of AlloP with 5 mum GABA did augment tonic current, which was not primarily through delta-containing receptors. Furthermore, AlloP decreased the membrane resistance and the number of action potentials of DGCs, but the impact on PV interneurons was weaker than on DGCs. Thus, our results indicate that hippocampal PV interneurons possess low sensitivity to AlloP and suggest they are unlikely contributors to mood-altering effects of neurosteroids through GABA effects.
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