UCSF

The physiological conditions within our bodies are remarkably stable. To maintain this internal stability (called ‘homeostasis’), we have evolved specialized neural systems that precisely regulate the physiological parameters that are critical for our survival. For example, the brain’s thirst circuit monitors the osmolarity and volume of the blood and fine-tunes drinking behavior, cardiovascular tone, and renal function in order to maintain fluid homeostasis.

Thirst has traditionally been viewed as a simple negative feedback response to changes in the blood. However, most natural drinking behavior is regulated too rapidly to be controlled by blood composition directly and instead appears to anticipate homeostatic perturbations before they arise. To address this paradox, we identified genetic markers for neural populations throughout the brain’s thirst circuit and used them as tools to investigate the origins of thirst.

Chapter one of this dissertation reviews our historical understanding of thirst and fluid homeostasis. Chapter two describes the first in vivo recordings of thirst neuron activity during behavior, which unexpectedly revealed that these cells—historically viewed as merely passive sensors of blood composition—also integrate sensory information from the oropharynx and gastrointestinal tract to predict the homeostatic consequences of eating and drinking. Chapter three describes the motivational mechanism underlying thirst. Chapter four describes a new mode of gut–brain communication that regulates thirst satiation. Together, these experiments have revealed fundamental organizing principles by which the brain monitors the state of the body in order to dynamically control ingestive behavior and maintain physiological homeostasis.