The goal of the renewal proposal is to uncover how developmental programs establish brain circuitry controlling critical social and non-social behaviors. Our previous findings studying amygdala development have lead to a developmental transcription factor-centric model in which we hypothesize that development, connectivity and innate behavioral specificity of limbic subcircuits are differentially controlled by the embryonic expressed transcription factors, Dbx1 and Foxp2. We will test this model in three aims in which we will: 1) determine the limbic connectivity patterns of Dbx1- and Foxp2-derived neurons (Specific Aim 1), 2) the cell adhesion molecules regulated by Dbx1 and Foxp2 (Specific Aim 2) and 3) the function of Dbx1 and Foxp2 in the formation/maintenance of medial amygdala circuit function and social and non- social innate behaviors (Specific Aim 3). Testing of this hypothesis will be accomplished using a diverse and powerful combination of state of the art conditional mouse genetics, neuronal circuit mapping and gene profiling approaches along with electrophysiology and innate behavior tasks. By comprehensively integrating data from multiple levels of analyses, we will uncover how developmental programs establish brain circuitry that controls motivational and innate social and non-social behaviors. Moreover, as amygdala dysfunction is a prime feature of a host of prevalent human social and emotional disorders, including drug-addictive behaviors and autism spectrum disorders, this work is critical toward understanding how brain circuit dysfunction leads to substance abuse and addictive behaviors.
Using cutting edge and cross-disciplinary approaches, this proposal is directed toward understanding how embryonic developmental programs establish brain circuitry regulating amygdala-based behaviors. Amygdala dysfunction is associated with prevalent emotional, social and motivational disorders such as addictive behaviors and autism spectrum disorders. Therefore elucidation of the mechanisms of amygdala development is critical for understanding how brain circuit dysfunction leads to substance abuse and addictive behaviors, as well as for designing rational interventional and therapeutic approaches.
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