Inhibitory synaptic control of social avoidance behavior

每6个美国人中就有1人报告患有终生抑郁症；然而，三分之一的抑郁症患者对目前的治疗方案有抵抗力。寻找更有效的药理学干预措施依赖于对情绪障碍背后的病理生理学有更好的基础科学理解。动物模型的使用，如慢性社会失败应激，加深了我们对压力易感性和弹性的生物学机制的理解。我们实验室以前的研究表明，在易受社会失败影响的小鼠中，伏隔核(NAC)中兴奋性突触的增加，这是一个对奖励途径至关重要的大脑区域。初步数据还显示，在慢性社会失败应激后，NAC中抑制性突触前终末减少。我们假设，抑制音在NAC中的下调是导致社交回避行为的压力易感性的基础。本研究旨在更全面地研究慢性社会挫败应激引起的NAc GABA能微回路抑制音的变化，并探讨快速放电的小白蛋白中间神经元在社交回避行为中的作用。

1 in 6 Americans report a lifetime prevalence of major depressive disorder; however, one-third of depressed patients are resistant to current treatments. The search for more effective pharmacological interventions relies on a better basic science understanding of the pathophysiology underlying mood disorders. The use of animal models, such as chronic social defeat stress, has furthered our understanding of biological mechanisms underlying susceptibility and resilience to stress. Previous studies in our lab showed an increase in excitatory synapses in the nucleus accumbens (NAc), a brain region critical to the reward pathway, in mice susceptible to social defeat. Preliminary data also shows a decrease in inhibitory presynaptic terminals in the NAc following chronic social defeat stress. We hypothesize that downregulation of inhibitory tone in the NAc underlies susceptibility to stress leading to social avoidance behavior. This proposal seeks to more fully examine chronic social defeat stress- induced changes to inhibitory tone in the NAc GABAergic microcircuit and to investigate the contribution of fast- spiking, parvalbumin interneurons to social avoidance behavior.