Inhibitory synaptic control of social avoidance behavior

每6个美国人中就有1人报告患有重度抑郁症；然而，三分之一的抑郁症患者对目前的治疗有抗药性。寻找更有效的药物干预依赖于对情绪障碍的病理生理学的更好的基础科学理解。使用动物模型，如慢性社会失败压力，进一步加深了我们对压力易感性和恢复力的生物学机制的理解。我们实验室之前的研究表明，在易受社交失败影响的小鼠中，伏隔核（NAc）的兴奋性突触增加，这是大脑中对奖励通路至关重要的区域。初步数据还显示，慢性社会失败应激后，NAc的抑制性突触前终末减少。我们假设NAc中抑制性音调的下调是导致社会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交失败应激引起的NAc gaba能微回路抑制张力的变化，并研究快速尖峰、小白蛋白中间神经元对社交回避行为的贡献。

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.