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

想象一下在夜晚走在黑暗的街道上。听到身后突然传来的脚步声，你感到害怕，心跳加速，准备逃跑--这是我们复杂情绪反应的一个方面。异常的情绪调节会导致严重的问题，并在焦虑症，抑郁症和精神分裂症中可见。这些疾病可以用影响血清素的药物治疗，但血清素作用于许多不同的大脑区域和受体。在抑郁症等疾病中，特定的大脑区域会出现异常，包括杏仁核（众所周知会影响情绪反应），还有海马体和前额叶皮质。这些结构如何有助于正常的情绪调节，出错，并受到血清素的影响，人们对此知之甚少。我将使用猴子的任务来测量感知的情绪偏差（抑郁症中看到的玻璃半空效应），以及心率，血压和行为如何改变对不可靠预测情绪事件的刺激的反应。我将研究海马体和前额叶皮层对情绪的生理和行为方面的贡献，方法是使用特定的药物使它们失活，并改变它们的血清素信号。这将提高我们对这些区域如何控制情绪的理解，以及对数百万人生活中的疾病的大脑基础的理解。

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.