GABAA receptor ε subunit expression in identified peptidergic neurons of the rat hypothalamus

Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro

“…Consistent with prior in situ hybridization study [22], in slices superfused with ACSF, the mRNA levels for ε subunit of GABA A R were significantly higher in the DM than the PF region (120±28 (SE) copies/ng of total RNA vs. 21±5, p<0.006; Fig. 1B).…”

“…We quantified mRNA levels for seven GABA A R subunits that are expressed in the posterior hypothalamus (α 1 , α 2 , α 3 , β 1 , β 2 , β 3 and ε) [22][23][24] in two anatomically adjacent but functionally different hypothalamic regions following three in vitro treatments: superfusion of slices with plain ACSF, GABA uptake blocker (NO-711), or the latter combined with the GABA A R antagonist, gabazine.…”

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

“…Like the γ 1 subunit, ε expression is limited to a small number of CNS regions and is enriched in hypothalamic/forebrain regions, including the mPOA and the ventromedial nucleus of the hypothalamus (VMN), that are involved in the generation of reproductive behaviors (for review, Clark and Henderson, 2003;Clark et al, 2006). Of particular relevance, ε subunit is expressed at abundant levels in gonadotropin releasing hormone (GnRH) neurons, and virtually all GnRH neurons in the mPOA/anterior hypothalamus express this subunit (Moragues et al, 2003).…”

“…A role for the ε subunit in imparting insensitivity to neurosteroid modulation is further indicated by studies of GnRH neurons within the mPOA/anterior forebrain, which express high levels of the ε subunit (Moragues et al, 2003): a very high concentration of allopregnanolone (5 μM) elicited only modest increases in mPSC amplitudes and prolongation of decay time in these neurons, while DHEAS (5 μM) moderately diminished peak amplitude with no change in decay kinetics (Sullivan and Moenter, 2003). It is interesting to speculate that GnRH neurons, which need to be exquisitely sensitive to changes in gonadal steroids, may be buffered from the influences of neurosteroids (whose concentrations will also vary with hormonal state) by expressing GABA A receptors whose subunit composition limits neurosteroid responsiveness.…”

“…Thus, it is tempting to postulate that allopregnanolone modulation of these extrasynaptic, rather than synaptic, conductances may be the critical factor in mediating the changes in oxytocin neuronal firing that occur during late pregnancy and parturition. Delta-containing receptors are known to give rise to most tonic, extrasynaptic conductances in other brain regions, however, given that δ subunit expression in the hypothalamus/basal forebrain is debatable (Fritschy and Mohler, 1995;Pirker et al, 2000) and expression of ε in this brain region is marked (Whiting et al, 1997;Sinkkonen et al, 2000;McIntyre et al, 2002), most notably in the GnRH neurons (Moragues et al, 2003), an intriguing possibility is that ε-containing receptors may play a comparable role in regulating tonic GABAergic conductances and allosteric modulation to both the endogenous neurosteroids and the AAS.…”