The original version of this story appeared in Quanta Magazine. Water is the most fundamental need for all life on Earth. Not every organism needs oxygen, and many make their own food. But for all creatures, from deep-sea microbes and slime molds to trees and humans, water is nonnegotiable. “The first act of life was the capture of water within a cell membrane,” a pair of neurobiologists wrote in a recent review. Ever since, cells have had to stay wet enough to stay alive. Water is the medium in which all chemical reactions in an organism take place, and those reactions are finely tuned to a narrow range of ratios between water and salt, another essential ingredient in life’s chemistry. The cells in your body are permeable to water, so if the water-salt balance of the surrounding fluid—blood, lymph, or cerebrospinal fluid, for example—is outside its healthy range, cells can swell or shrink, shrivel, or potentially burst. An imbalance can cause brain cells to malfunction, losing their ability to manage ion concentrations across their membranes and propagate action potentials. Although these effects of insufficient water are felt by every cell in the body, cells themselves do not cry out in thirst. Instead, it’s the brain that monitors the body’s water levels and manifests the experience of thirst—a dry tongue, hot throat, and rapid onset of malaise—which compels a behavior: acquire water. “These neural circuits that control hunger and thirst are located deep in primitive brain structures like the hypothalamus and brain stem,” said Zachary Knight, a neuroscientist at the University of California, San Francisco, who recently coauthored a review paper in Neuron on the neurobiology of thirst. Camels don’t experience thirst the same way we do: They burn fat stores or draw stored gallons from their stomachs when they need water. Moaz Tobok, CC0 Creative Commons license via Pexels Because these brain areas are difficult to study—due not only to their location but also to their composition, with many different cell types and crisscrossed circuitry—it’s only in the past decade or so that neuroscientists have begun to understand how thirst fundamentally works. The body, researchers have found, is filled with sensors that feed clues to the brain about how much water or salt an organism needs to consume. How those sensors work, or what they even are, continues to elude scientists. Their existence offers a tantalizing insight: Water may be fundamental to life, but thirst is an educated guess. Environmental Sensing To understand thirst in mammals, think of it less as the body stating a fact to the brain—“I need water”—and more as the brain monitoring its environment, the body. Like an ecologist sampling a river, the brain examines blood’s chemical composition to learn what the body needs. In nearly all cases, the so-called blood-brain barrier protects the brain from bacteria, viruses, or other dangers circulating in the blood. But there are a few exceptions where the brain directly interfaces with blood, including in the circumventricular organs, deep in the brain near the hypothalamus. Two of these organs—the vascular organ of lamina terminalis (OVLT) and the subfornical organ (SFO)—are sensory organs not unlike a nose or an ear. They act like scientists dipping a bucket into the body’s river of blood to test its health. The brain infers the body’s salt and water needs from that data and funnels the information to neural circuits in even deeper regions, which then can trigger what we experience as thirst—the scratchy throat, dry mouth, and foggy brain that accompany desire for water.