Stress-related disorders, including major depression, represent the most leading cause of health problem worldwide and a large part of depressive patients remain insensitive to treatments. Hence, the uncovering of the relevant processes involved in these disorders is of crucial importance. Recent works suggest that hippocampal neurogenesis is involved in the pathophysiology and the treatment of these disorders. The ability of the adult mammals, including humans, to produce new neurons is a fascinating process that has generated considerable interests, but their precise function remains poorly understood. In this project, we aim to understand how the production of new neurons can influence hippocampal network activity and underlie antidepressant effects. We hypothesize that antidepressants, by increasing neurogenesis, may strengthen stress integration by improving the coupling between contextual information and emotional state. Accordingly, we will examine whether chronic stress, antidepressant and viral-mediated inhibition of neurogenesis in animal models can alter hippocampal cell activity, behavioral performance and stress system (HPA) activation in “emotionally-relevant” environments. A putative alteration of hippocampal activity in chronic stressed animals could be responsible for disrupted behavioral responses and emotional state, as occurring in depression. Inhibition of hippocampal neurogenesis will help to determine whether antidepressants require new neurons to reverse the detrimental effects of chronic stress on hippocampal activity, facilitating suited behavioral responses and recovery. In conclusion, investigating the specific contribution of hippocampal neurogenesis in these processes will be essential for the understanding of the normal brain functioning in encoding new representations as well as for the characterization of pathological conditions associated to stress-related disorders and of the therapeutic potentialities of manipulating neurogenesis.
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