UCSF

The termination of food and water consumption is traditionally thought to depend on gastrointestinal and post-absorptive feedback. However, sensory signals generated during ingestion begin regulating consumption before nutrients or water reach the stomach. The mechanisms by which these pre-gastric signals regulate satiation and interact with post-ingestive feedback remain poorly understood. In this dissertation, I investigated the neural basis of pre-gastric satiation using a sham ingestion paradigm in rats, which isolates pre-gastric signals from post-gastric feedback, combined with transgenic rat models, neural recordings, and optogenetic manipulations.I found that pre-gastric signals make a major contribution to rapid thirst quenching by inhibiting thirst-promoting neurons in the median preoptic nucleus. This inhibition progressively weakens when oral water cues are repeatedly uncoupled from rehydration, demonstrating that pre-gastric thirst quenching is learned rather than innate. I further show that this learning is bidirectional and reflects the predicted physiological consequences of ingestion. In parallel, I found that pre-gastric satiation during feeding is nutrient-specific and depends on oral detection of calories rather than sweetness alone, with evidence supporting a role for oral glucose sensing through SGLT1. Together, these findings demonstrate that pre-gastric satiation is a learned predictive process that links oral sensory cues with their post-ingestive consequences to tightly regulate ongoing consumption. This work provides new insights into the neural mechanisms underlying the brain's control of meal size and fluid intake.