VTA microcircuit dynamics during chronic stress

摘要 在这个项目中，我们将研究腹侧被盖区(VTA)的抑制动力学。 慢性压力。GABA能神经元占VTA神经元的35%，但相对鲜为人知 关于他们的。这些细胞是邻近的多巴胺能神经元的关键调节器，并且非常健壮。 被急性压力激活的。因此，VTA GABA神经元可能是应激反应的重要介体 对VTA的影响。然而，这些神经元如何应对慢性应激仍是个未知数。在……里面 这项建议，我们将采取多学科的方法，利用电生理学，光遗传学， 行为，和纤维光度法，以解决长期应激导致持续性的假设 VTA-GABA神经元的过度活动是出现适应不良行为的基础 回应。在第一个目标中，我们将研究VTA多巴胺神经元抑制的动力学。 应激过程中的VTA-GABA神经元。在第二部分中，我们将调查中国人的活动和力量 VTA GABA神经元的突触输入在应激过程中会发生变化。在第三个目标中，我们将检查 VTA-GABA神经元在体内的活动是否有助于个体差异的出现 社交快感缺乏症后压力。这些研究有可能对我们的 了解压力是如何改变奖励系统的，这可能会带来新的途径 抑郁症和其他应激相关疾病的治疗方法的发展。

ABSTRACT In this project, we will investigate the dynamics of inhibition in the ventral tegmental area (VTA) during chronic stress. GABAergic neurons make up 35% of neurons in the VTA, but relatively little is known about them. These cells are critical regulators of neighboring dopaminergic neurons, and are robustly activated by acute stress. VTA GABA neurons are thus poised to be a significant mediator of stress’s effects on the VTA. It remains unknown, however, how these neurons respond to chronic stress. In this proposal, we will take a multidisciplinary approach, utilizing electrophysiology, optogenetics, behavior, and fiber photometry to address the hypothesis that chronic stress leads to persistent hyperactivity of VTA GABA neurons and that this underlies the emergence of maladaptive behavioral responses. In the first aim, we will examine the dynamics of inhibition of VTA dopamine neurons by VTA GABA neurons during stress. In the second, we will investigate how activity of and strength of synaptic inputs onto VTA GABA neurons changes during stress. In the third aim, we will examine whether in vivo activity of VTA GABA neurons contributes to individual differences in the emergence of social anhedonia post-stress. These studies hold the potential to contribute significantly to our understanding of how the reward system is altered by stress and may lead to novel avenues for the development of therapeutic treatments for depression and other stress-linked disorders.