Acute strengthening of hypothalamic paraventricular nucleus GABAergic inhibition by glutamatergic input from the median preoptic nucleus is not observed in water deprived mice

Abstract

Our previous work in hypothalamic paraventricular nucleus (PVN) slice preparations showed that increasing ambient glutamate, either by bath application or local synaptic release, acutely strengthens GABAergic transmission by 20-30% through a mechanism dependent on glutamate uptake, likely by the neuronal transporter EAAT3 (EAAC1). Here, we first investigated the extent to which this homeostatic mechanism, termed glutamate-GABA strengthening or GGS, is recruited by glutamatergic inputs from the median preoptic nucleus (MnPO). Next, we investigated the impact of dehydration, which increases PVN glutamatergic input from the MnPO, on MnPO-driven PVN GGS. PVN neurons that received glutamatergic input from MnPO as well as GABAergic input from the surrounding peri-nuclear zone (PNZ) were identified in angled horizontal slices prepared from euhydrated (EUH) and 72 h water deprived (WD) male vGAT-ChR2 mice (C57Bl/6 BGND). Preliminary findings indicate that MnPO EPSCs evoked by 1 Hz electrical stimulation increased the amplitude of IPSCs (+22%) evoked by photo-stimulating ChR2-expressing GABAergic PNZ neurons every 15 s (n=4 cells). Recruitment of PVN GGS by glutamatergic MnPO inputs was absent in slices from WD mice (n=3 cells). Western blot of PVN whole-cell lysate from male C57Bl/6 WT mice revealed that EAAT3 expression was increased (+32%), not decreased, in the WD compared to EUH group (n=18 mice/group), raising the possibility that dehydration maximally recruits PVN GGS. Ongoing studies seek to confirm the later possibility and quantify the contribution of the GGS mechanism in PVN-driven sympathetic and hemodynamic responses to dehydration. Support: NS115072 and MH093320 (GMT) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.