The stress response of mammals is a complex response to stimuli such as severe environmental change that might otherwise be deleterious to the whole organism. The appropriate response requires the interplay of the nervous system and production of certain hormones that prepare the animal to adapt physiologically to the stressful challenge. Certain peptide neurohormones and neurotransmitters in the key brain region of the hypothalamus are critically involved in stress-activation, but the fine regulation of these basic mechanisms is poorly understood. This project is designed to uncover the specific role of a recently discovered neuropeptide, PACAP (pituitary adenylate cyclase-activating polypeptide), in stress-activation in the hypothalamus. Neuropeptides are small, protein-like molecules that serve specific functions in the brain, and help establish or maintain communication between nerve cells (neurons). PACAP is an intriguing molecule presumed to have important functions in adaptive functions such as stress-activation. Biochemical, molecular, anatomical and immunocyctochemical methods are used in this research to determine where, when and how PACAP regulates the gene expression and the release of a key hormone, CRH (corticotropin-releasing hormone) from a population of cells in the hypothalamus.<br/> Results will be important not only for neuroendocrinology, but also potentially for many systems where PACAP may have a novel role as a co-transmitter with classical neurotransmitters like catecholamines. This project will also have an impact on the development of the career of a young investigator.