Grant: CIHR Fellowship

Major depressive disorder and other forms of severe depression are estimated to affect more than 1 in 10 Canadians over the course of their lifetime. The high prevalence of depression in our society constitutes a growing social and economic burden. As many as one third of those affected develop a chronic form of depression that is unresponsive to antidepressant medications. In order to address the shortcomings of current therapies, the medical and research communities would greatly benefit from a deeper understanding of the changes that occur in the brain during depression. Current research indicates that regions of the brain that normally encode motivation and pleasure no longer communicate properly in depressed individuals, particularly following repeated stressful events. It is believed that this miswiring of the brain's reward circuits then leads to diminished responses to stimuli that normally elicit pleasure and the motivation to work for reward. The research we propose here aims to better understand how the brain's reward circuits are altered by chronic stress in mice, and how we can reverse these changes to restore normal behaviour. We are particularly interested in a region of the brain called the ventral pallidum (VP), which contains different classes of specialized cells that communicate to other cells of the brain's reward circuits. By using a set of innovative neuroscience research tools we will study how two classes of VP cells are anatomically connected to and communicate with other cells in the brain. In order to restore normal levels of motivation and social behaviour we will then control how VP cells communicate to other brain cells. We anticipate that our research will provide unprecedented insight into how depression is encoded by the activity of specific cells in the brain. This information will be beneficial for the design of a new generation of antidepressant therapeutics that effectively addresses the current treatment gap.