This application is focused on the study of the development of the innate limbic system behaviors, with a particular emphasis on the hypothalamus. The hypothalamus receives major inputs from limbic system structures, including the amygdala, and functions in innate aversive and motivational behaviors such as stress and feeding. Our previous studies have identified distinct progenitor pools (Dbx1+ cells) in the developing telencephalon that contribute to postnatal neuronal cell diversity in hypothalamic subdivisions. Deletion of the Dbx1 gene in the hypothalamus caused changes in gene expression in embryonic and adult animals, potentially explaining the feeding and stress phenotype of these conditional knockouts. Based on this work, this project will test two hypotheses. First, it will test the hypothesis that Dbx1 is required for the development of postnatal hypothalamus neurons. Second, it will test the hypothesis that Dbx1 is required for hypothalamic-dependent innate behaviors such as feeding and stress. Testing of these hypotheses will be accomplished using the genetic precision of conditional loss of function transgenic mice.
The mammalian hypothalamus is the major processing center of brain's limbic system, a circuit that coordinates appropriate behavioral responses to stimuli with aversive and motivational salience. Hypothalamic dysfunction is associated with numerous brain disorders including addictive behavior, feeding and anxiety disorders. This proposal is directed toward understanding the genetic and cellular basis of hypothalamic development, and thus will provide valuable insight into human disorders in which hypothalamus function is altered.