Temporal Specification of Basal Forebrain Circuitry

Project Summary The septal complex which regulates a wide range of social, and emotional behaviors can be classified into medial (MS) and lateral (LS) regions. The medial septum is composed of cholinergic and GABAergic neurons that primarily project to the hippocampus. The lateral septum is composed of a diverse array of GABAergic projection neurons that receives reciprocal input from numerous brain regions known to regulate emotional and motivational states. The lateral septal nuclei are strongly implicated in stress and anxiety where previous studies indicate a role for the septum in both promoting and suppressing anxiety related behavior, including circuits involved in mediating enduring behavioral changes resulting from early life stress and social trauma. Dysfunction of septal neurons is thought to play a significant role in the pathophysiology of a variety of psychiatric disorders including schizophrenia, bipolar disorder, depression and anxiety-related disorders. Despite our growing appreciation for the importance of septal nuclei circuit function in modulating social, emotional and affective behaviors we know very little about the specific functions of the diverse septal neuron types and even less about the developmental mechanisms that create this diversity. The overall goal of this research proposal is to identify the key genetic and molecular pathways that underlie the developmental logic for the functional specialization of diverse neuronal cell types in the septum. Our studies will provide a framework for assessing the development and behavioral function of other septal neuron types and uncover targets for novel treatments for neuropsychiatric disorders that may arise from septal circuit dysfunction.