Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Stress although unpleasant, is both necessary and adaptive. Prolonged stress however, is not adaptive, and can result in a variety of anxiety related disorders, such as Post traumatic stress disorder (PTSD). An important factor determining an individual's susceptibility to stress related disorders is the peptide chemical messenger Neuropeptide Y (NPY). NPY is an important naturally occurring anti-anxiety compound, exerting much of its effects on the Basolateral amygdala (BLA) a brain area important in regulating emotions. NPY likely produces its anti-stress effects by decreasing output signaling from BLA pyramidal cells. Several lines of evidence suggest that the anti-anxiety actions of NPY are mediated by the Y1 receptor, while the Y2 receptor mediates pro-anxiety effects. This project focuses on the mechanisms within the BLA by which Y2 receptors may induce anxiety. Published data indicates that Y1 receptors act to inhibit BLA pyramidal neurons directly while; preliminary data indicates Y2 receptors act on interneurons sending inhibitory signals to pyramidal cells. The specific aim of this project will be to investigate the role Y2 receptors play in regulating the complex activity of BLA interneurons. This will be investigated using BLA containing rodent brain slices; with some experiments using mice expressing green fluorescent protein (GFP) labeled interneurons. The whole cell patch clamp technique will be used to directly measure electrical properties of BLA neurons while; targeted GFP expression will allow identification of specific BLA interneurons. By applying drugs that selectively activate or block Y1 or Y2 receptors we will measure electrical changes in patched cells when Y1 or Y2 receptors are selectively targeted. Through these investigations we hope to further understand the subtleties of NPY's anti-anxiety and pro-anxiety mechanisms. This in turn will provide novel targets for drugs potentially useful for treating anxiety related illness such as PSTD.