Projection-Specific Serotonin Signaling in Homeostatic and Motivated Behaviors

To survive in complex environments, animals must flexibly integrate internal needs with external features to guide behavior. For example, the decision to leave safety to search for food depends on both the intensity of hunger (internal need) and environmental demands (e.g., threat level, resource availability). How does the brain integrate these internal and external signals? This process is thought to rely on neuromodulators like serotonin, which encodes factors related to both physiological state and environmental context. However, how the serotonin system integrates this information to shape behavior remains unclear.

Although serotonin is one of the most impactful and widely released neuromodulators in the brain, its precise roles in behavior and physiology remain debated. A key reason for this confusion is that most studies have treated serotonin neurons as a uniform population, despite growing evidence of anatomical and functional heterogeneity within the serotonin system. Recent work shows that serotonin neurons form distinct subgroups based on non-overlapping projection patterns, suggesting that these subpopulations may support specialized behavioral functions. The significance of this organization to behavior and physiology, however, is still unknown.

In my postdoctoral research, I aim to address this knowledge gap by asking how distinct serotonin subsystems encode internal states and environmental cues to control behavior. Focusing on foraging behavior in mice, I will use viral-genetic tools to modulate specific serotonin subpopulations and assess the impact on behavioral choices. I will then combine high-density neural recordings with computational modeling to characterize how these subtypes encode information and modulate downstream neural activity. By deconstructing serotonin into projection-defined subsystems, this work will clarify persistent questions regarding the functional role of serotonin in the brain. Given serotonin’s broad relevance to human health and psychiatric illness, these insights may help guide new strategies for understanding and treating mental health disorders.