Development of the basal telencephalic limbic system

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DESCRIPTION (provided by applicant): This revision application is in response to NOT-OD-09-058 "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications" and is focused on the study of the development and function of the medial nucleus of the amygdala. The medial amygdala nucleus is a central structure of limbic system brain circuitry that regulates feeding, reproductive and defensive behaviors. Our recent studies have identified unique developmental mechanisms in which homeodomain-expressing Dbx1+ progenitor pools are dedicated for the generation of medial amygdala neuronal cell diversity. Expanding on these findings, in this project we will examine two distinct aspects of medial amygdala development and function. First, we will study the function of Dbx1 in the specification of medial amygdala inhibitory output neurons and circuitry. This will be accomplished by conditional mutagenesis approaches. Second, using previously generated knockin mice in which Dbx1-derived cells are permanently marked, we will comprehensively examine the functional synaptic and electrical connectivity of medial amygdala inhibitory output neurons. Thus, these studies will provide a link between brain development and brain function. PUBLIC HEALTH RELEVANCE: The mammalian amygdala is a central structure of the brain's limbic system, a brain circuit that coordinates appropriate behavioral responses to stimuli with emotional and motivational salience. Amygdala dysfunction is associated with numerous brain disorders including addictive behavior and developmental disorders such as autism spectrum disorders. This proposal is directed toward understanding the link between development and function of the medial amygdala nucleus, and thus will provide valuable insight into human disorders in which amygdala function is altered.