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。 在长期的压力下。GABA能神经元占VTA神经元的35%，但相对较少 知道他们的事。这些细胞是邻近的多巴胺能神经元的关键调节器，并且 被剧烈的压力强烈地激活。因此，VTA-GABA神经元可能是一种重要的介质。 压力对VTA的影响。然而，目前尚不清楚这些神经元是如何对慢性 压力。在这项提案中，我们将采取多学科方法，利用电生理学， 光遗传学、行为学和纤维光度学解决慢性应激导致 VTA-GABA神经元的持续性多动，这是出现适应不良的基础 行为反应。在第一个目标中，我们将研究VTA多巴胺的抑制动力学。 VTA GABA神经元在应激过程中的作用。在第二节中，我们将调查和的活动 VTA GABA神经元的突触输入强度在应激过程中发生变化。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对个体差异有贡献 应激后出现社会性快感缺失。这些研究具有做出重大贡献的潜力 我们对压力如何改变奖赏系统的理解，并可能导致新的途径 用于开发抑郁症和其他与压力相关的疾病的治疗方法。

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.