Grant: Project Grant

One of the most conspicuous characteristics of any organism is its ability to react to salient stimuli with an appropriate behavioral response that maximizes survival and minimizes threatening or unpleasant events. In mammals, emotions have been proposed as the evolutionary strategy to detect changes, either internally or from the environment, to organize proper behavioral responses. When negative events occur, such as stress, processing of these signals in the brain becomes inappropriate and leads to cognitive and behavioral deficits characteristic of mood disorders. The implication of serotonin in the control of emotions and action selection have been widely described. Its role in mood control is also well-recognized, as exemplified by the fact that pharmacological antidepressants are based on the modulation of serotonin in the brain. However, because of the complexity of serotoninergic neural pathways in the brain, the main role of serotonin in the control of emotion, cognition and behavior is still elusive. In this research proposal, we will use innovative approaches to measure and manipulate, in real-time and freely moving mice, specific serotoninergic neural pathways. When combined with different behavioral tests commonly used with mice, these approaches will allow us to precisely dissect how serotoninergic neural pathways in the brain process emotions to organize proper behavioral responses. We will also perform electrophysiological recordings at these serotoninergic pathways from normal and depressed mice to reveal cellular and molecular dysfunctions underlying cognitive and behavioral deficits associated with mood disorders. In the long term, our work will lead in the development of new therapeutic approaches to ultimately help people suffering from mood disorders.