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.