Stress responses in all species are the result of the culmination of sensory and memory information processed by different brain regions, each of which is designed to handle a set of unique inputs. The ultimate goal of a properly executed stress response is to assess the danger and either confront or avoid the threat. In some cases, repeated stress or exposure to extreme stresses, such as combat, puts undue pressure on the individual resulting in continued anxiety which can manifest as anxiety-related stress disorders such as panic disorder, posttraumatic stress disorder (PTSD) or depression. Conversely, some individuals thrive in the face of continued stress and are resistant to the adverse effects of stress. The mechanisms underlying individual differences in stress responses have not been elucidated and the description of which is in its scientific infancy. Neuropeptide Y (NPY) has received considerable attention as an endogenous anxiolytic compound. Recent studies describe an inverse correlation between NPY and the incidence of PTSD in combat veterans. Our preliminary data demonstrate that administration of NPY in the basolateral amygdala (BLA) decreases stress responses in rats and produces persistent stress resilience. We also found that a conditioned fear (emotional) stress increases NPY expression within the BLA, an area critical for the generation of emotional stress behaviors and memories. These proposed studies are designed to examine the contribution of NPY receptor activation to stress resilience and to elucidate the cellular and molecular mechanisms underlying NPY receptor signaling in the BLA. The following aims will be addressed: 1) Identify the source(s) of NPY fibers innervation neurons of the BLA and the neurochemical phenotype of neurons expressing NPY receptors;2) Determine the cellular responses to administration of NPY and NPY receptor selective ligands;and 3) Examine the cellular and molecular mechanisms that are associated with anxiolysis and stress resilience in animals treated with injections of NPY in the BLA. A multidisciplinary approach using anatomical, behavioral, electrophysiological and molecular biological methodologies will be employed in the performance of this research. The results from this work will be of importance in understanding the circuitry underlying the generation of stress resilience.
Exposure to stress and anxiety can lead to the development of a number of anxiety-related diseases such as depression, panic disorder and PTSD and neuropeptide Y (NPY) has been implicated as being a protective factor to the generation of anxiety and related illnesses. The current proposal intends to examine the NPY circuits within the BLA as they relate to the control of stress responses and resilience. It is anticipated that these results will provide exciting new data on the role and regulation of a stress-reducing peptide within the brain and shed new light on the control of anxiety and additional mechanism of anxiety treatment.
