Serotoninergic modulation of hippocampal-prefrontal circuitry and the control of negative emotional regulation

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Imagine walking down a dark street at night. Hearing unexpected footsteps behind you, you feel fear, your heart races, and you get ready to run - aspects of our complex emotional response. Abnormal emotional regulation causes major problems, and is seen in anxiety, depression, and schizophrenia. These disorders are treated with drugs influencing serotonin, but serotonin acts on many different brain regions and receptors. In disorders such as depression, specific brain regions are abnormal, including the amygdala (well known to influence emotional responses) but also the hippocampus and prefrontal cortex. How these structures contribute to normal emotional regulation, go wrong, and are influenced by serotonin is poorly understood. I will use tasks in monkeys that measure emotional biasing of perception (the glass half empty effect seen in depression), and how heart rate, blood pressure and behaviour alter in response to stimuli that unreliably predict emotional events. I will investigate the contribution of the hippocampus and prefrontal cortex to physiological and behavioural aspects of emotion by inactivating them, and altering their serotonin signalling using specific drugs. This will improve our understanding of how these regions control emotions and of the brain basis of disorders blighting the lives of millions.