9222263 Birkle Corticotropin-releasing factor (CRF), a 41-amino acid neuropeptide, plays a central role in the physiological response to stress and anxiety. Behavioral studies have demonstrated that injection of this neuropeptide into the brain mimics anxiety-like and stress-like reactions possibly by its activation of the hypothalamic-pituitary-adrenal axis. Indeed under certain conditions, CRF is released into the portal system from neurons in the hypothalamus, stimulates the pituitary to secrete adrenocorticotropic hormone (ACTH) which then acts on the adrenal to release glucocorticoids. Recently, CRF-secreting neurons have been shown to be not only located in the hypothalamic area but also in limbic structures, including the amygdala. This is exciting since the amygdala is considered to be the seat of emotional responses like fear and rage. Dr. Birkle will examine the regulation of the release of CRF from neurons in the amygdala. She will use neurons from this brain region that are isolated from developing tissue and grown in culture. This technique offers the advantage of creating a pure population of nerve cells in an easily manipulated environment. Dr. Birkle will first identify neurons that contain CRF receptors and then determine what type of neurotransmitter are also located in these cells. She will use then determine the effects of exposure to these neurochemical mediators and their antagonists on the release of CRF. The results will provide new insights about the regulation of CRF in extrahypothalamic sites. Since CRF plays a pivotal role in the expression of anxiety and autonomic responses to stressful events, the results will provide a better understanding about how the brain, as a whole, integrates the multicomponent response to stress and anxiety. Moreover, this work will increase our knowledge of the neurochemical processes that lead to the experience of anxiety and will provide direction for the development of better preventi on and therapy for this disorder. ***
