Optogenetic stimulation of distinct populations of anterior preoptic neurons reveals a locus for the reciprocal control of thirst

Abstract

The median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT) regulates hydro‐mineral homeostasis in mammals. The neurochemical composition of this region is complex and the possibility of divergent roles for MnPO/OVLT neurons in thirst regulation has never been addressed. To this end, we injected a Cre‐dependent Channelrhodopsin2‐mCherry viral vector into the MnPO/OVLT of VGluT2‐ires‐Cre and VGAT‐ires‐Cre mice to selectively stimulate excitatory and inhibitory neurons respectively. Stimulation of excitatory MnPO/OVLT neurons caused water consumption in satiated mice (N=8). Water and physiological saline consumption during stimulation declined with successive trials over a 15 minute period, and fully recovered after 1 hour of rest, suggesting a pre‐systemic feedback gating of stimulus‐induced ”thirst”. Photostimulation of inhibitory MnPO/OVLT neurons reduced water consumption by 30% during 30 minutes of water access in dehydrated mice (N=8), but had no effect on food consumption following food deprivation. Axonal tracing of MnPO/OVLT excitatory and inhibitory neurons revealed overlapping innervation of areas important in hydro‐mineral homeostasis, including the paraventricular nucleus of the hypothalamus, sub‐fornical organ and supra‐optic nucleus. Together, these result indicate that the MnPO/OVLT region exerts a bi‐directional influence on thirst.Support or Funding InformationNational Health and Medical Research Council of Australia Early Career Fellowship (GNT1052674) (to S.B.A.)NIH‐NINDS R25 #NS070682 (to J.C.G.) NIH NS072337 (to C.B.S.)