The Neural Basis of a Thirst-dependent Odor Spotlight

Abstract

The perception of odors is critical for driving physiologically relevant behaviors. The olfactory system enables mice to interpret their chemosensory environment and elicit dynamic behavioral responses that restore homeostasis, enable reproduction, and ensure survival1–4. Many odors derive meaning and behavioral relevance from learned experience, behavioral context, and internal state. Understanding how internal states, such as hunger and thirst, modulate olfactory circuits to drive selective attraction to odors that predict essential resources remains a fundamental question in neuroscience. In this thesis, I review our current understanding of the neural circuits that mediate odor perception and how internal states exert differential control over odor processing and behavior. By manipulating the activity of underlying thirst circuits, I investigate how thirst reshapes behavioral responses to odors. I identify hypothalamic median preoptic nucleus (MnPO) neurons as central integrators of thirst required for driving attraction to water-predictive odors over other attractive olfactory cues. Among the multiple projection targets of MnPO neurons, inhibition of projections to the paraventricular thalamus (PVT) reveals a selective and necessary relay for coupling internal state signals with state-appropriate odor attraction. I also explore the molecular features of MnPO neurons that could mediate thirst-dependent odor attraction. Together, these studies help define how thirst influences olfactory responses and highlight general principles about how animals represent and process their internal states to selectively influence odor processing and behavior.