Grant: Project Grant

The stress response is composed of an array of endpoints including alterations in hormone secretion and the generation of states of heightened emotionality, such as anxiety. The amygdala is a brain region known to be important for the regulation of emotional states, and it is also well known to be activated by stress, yet our understanding of how changes in neural activity within the amygdala results in the generation of a stress response is still poorly understood. Establishing the circuit and neurochemical basis for how the amygdala regulates the stress response has a high degree of translational importance as the amygdala is known to be hyperactive in mood, anxiety and trauma related disorders, and normalization of this hyperactivity has been associated with disease remission suggesting that this hyperactivity is directly related to the development and maintenance of stress-related psychiatric conditions. As such, understanding which neurochemicals are involved in increasing or decreasing stress-induced activation of the amygdala may be important for furthering our understanding of the biology of how stress exposure relates to the development of psychiatric disorders. The aim of this proposal is to establish which neural circuits emanating from, and cell types within, the amygdala are responsive to stress and how their activity relates to the generation of a stress response. More so, this proposal will also focus on understanding the mechanisms by which neurochemicals, which are known to be both anti-stress or pro-stress, regulate these discrete neural circuits and cells. This information, in turn, may be utilized for the development of targeted drug based approaches to psychiatric illnesses based on their ability to regulate stress-induced activation of amygdala circuits.