Grant: Operating Grant

Anxiety is a protective emotion arising in anticipation of a future or potential threat. In its pathological form, anxiety becomes exaggerated and uncontrollable, leading to debilitating mental disorders. Approximately 20% of the general population suffers from anxiety disorders at some point in their life, with a yearly estimated financial cost of more than $65 billion in Canada alone. One of the most pressing needs and exciting research avenues into anxiety disorders is to identify neural elements that are causally involved in the diseases' core symptoms. Recent advances in neuroscience research tools such as light-sensitive ion channels (optogenetics) and designer receptors exclusively activated by designer drugs (DREADD pharmacogenetics) now permit the experimental manipulation of a very selective group of neurons in intact and freely moving animals. Using these new genetics tools, we will investigate how neurons in the hippocampus and their selective connections control anxiety behaviours. First, we will selectively activate or inhibit neural inputs from the ventral hippocampus (vHPC) to the amygdala and examine how this manipulation influences anxiety behaviours. Second, we will inhibit two non-overlapping populations of inhibitory GABA neurons in the vHPC, parvalbumin-GABA neurons (PV-GABA) and cholecystokinin-GABA (CCK-GABA) neurons, and assess the behavioural effects on anxiety. We anticipate that the grant will lead to a better understanding of how the limbic structures and their cellular components communicate to maintain appropriate anxiety behaviours, and provide helpful insights into the value of neural circuits in the hippocampus as potential therapeutic targets for treating anxiety disorders.