Suppression of neurons in circumventricular organs enables months-long survival without water in thirteen-lined ground squirrels

Water deprivation is a life-threatening condition that engages a protective physiological response to couple osmolyte retention with potentiation of thirst. This response, typical for most mammals, safeguards against short-term water deprivation, but fails in the long-term. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) employ the short-term response during summer, whereas during winter they lack thirst and survive without water for months. Here, we show that long-term thirst suppression occurs despite hormonal and behavioral signs of a dramatic fluid deficit and originates from hypoactivity of neurons in the circumventricular organs, which exhibit marked functional suppression during winter that blunts their sensitivity to thirst cues. Our work reveals a remarkable capacity of the evolutionarily conserved brain regions which control fluid homeostasis in mammals to enable long-term survival without water. Gene expression analysis and differential transcriptomics of the subfornical organ (n = 5 biological replicates) across active (non-hibernating) and interbout arousal (IBA) (hibernating) states in thirteen-lined ground squirrel.