Abstract
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) use the short-term response during summer, whereas during winter, they lack thirst and survive without water for months. In this work, we show that long-term thirst suppression occurs despite hormonal and behavioral signs of a substantial 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 notable capacity of the evolutionarily conserved brain regions that control fluid homeostasis in mammals to enable long-term survival without water.