Spatio-molecular and functional interrogation of serotonin subsystems

Dysfunction of complex neural circuits is implicated in neuropsychiatric disorders such as depression. The serotonin system has long been linked to the etiology of depression, as well as its treatment. However, the mechanistic role of serotonin signalling in the disorder and its treatment is still uncertain.

Furthermore, the heterogeneity of the serotonin neurons themselves is usually not taken into account when deciphering their role.

Our preliminary data identified two anatomically distinct and molecularly-defined serotonin subpopulations which are oppositely-regulated by antidepressant treatment.

The aim of this project is to perform a comprehensive analysis of these two novel serotonin subpopulations which may play opposing roles in mood regulation.

The project will untangle their anatomy, define their wiring and communication with the forebrain, and link their activity and function to separate facets of depression-related behavior.

The approach is based on spatial sequencing, viral-genetic tools, and state-of-the-art imaging and neural perturbation techniques during rodent behavioral assays.

This molecular and circuit interrogation will advance our understanding of the biology of mood regulation and further the development of new therapeutics.