Project Summary As a brain-wide neuromodulator, serotonin regulates a vast array of cognitive and emotional functions. It can potently induce plasticity in the adult brain. And with this power, it can promote learning and open windows for change and healing in neuropsychiatric conditions. It also has important roles in adaptive behavioral responses to stress, affiliative social behavior, aggression, and sleep. It is no wonder that serotonergic agents are widely used in psychiatry across several diagnoses. However, current treatments have many limitations. Most affect the serotonin system globally without regard to its underlying heterogeneity. To modulate the system in a targeted way, we need to understand how it is wired, and what each wire does. Serotonergic neurons in the dorsal and medial raphe nuclei send axonal projections throughout the entire brain. In this project, we will map these projections, with single cell resolution barcoding approach, to all their major brain targets. We will determine the strength of the projection to each target, and we will determine which target areas are coregulated by collateral projections, forming subnetworks. Furthermore, we will determine the molecular and functional identity of the neurons in each projection. Identifying the anatomical, molecular, and functional brain-wide serotonergic subnetworks could lead to new approaches for targeted therapies.