The septum is a structure in the basal forebrain that has critical roles in regulating emotional states including fear, anxiety and depression. Despite our growing appreciation for the importance of lateral septal circuit function in modulating emotional states, we know very little about the specific functions of the diverse septal neuron cell types and even less about the developmental mechanisms that create this diversity. We have identified the transcriptional regulator Prdm16 (Positive Regulatory Domain- containing 16), as being a critical component for regulating the production of distinct subtypes of neurons in the lateral septum. Our studies of Prdm16 serve as an entry point to understanding the relevant genetic programs and progenitor types regulating the development and specification of diverse septal neuron subtypes. In this proposal we plan to utilize single-cell RNA sequencing to map the developmental trajectories and overall diversity of neuronal cell types in the septum. The results from these studies will provide a foundation for understanding the development and function of temporally specified septum neuron types, and their contribution to behavioral circuits.
The septal nuclei of the basal forebrain critically regulates a number of behavioral processes related to mood, motivation, and anxiety, yet very little is known about the mechanisms that govern its development. Understanding the cellular and molecular mechanisms of septal circuit assembly could lead to the identification of new therapeutic targets and strategies for the treatment of neuropsychiatric disorders.