Determining astrocytic contributions to memory-related dimensions of PTSD

项目总结 创伤后应激障碍(PTSD)是一种破坏性的神经精神障碍，在 精神创伤。既往的压力暴露史显著增加了在以下情况下发生创伤后应激障碍的可能性 创伤性事件。消退性学习障碍是创伤后应激障碍的一种衰弱和核心症状。这种无能为力 了解以前与创伤有关的刺激不再具有威胁性，导致不适应的恐惧表达 对这些刺激的反应。减少压力导致的灭绝学习缺陷的努力包括识别 应激引起的大脑分子通路的紊乱。这项研究的大部分工作要么治疗了大脑 这些区域是同质的细胞群体，或者主要集中在神经元。而胶质细胞是人口最多的 神经系统中的细胞，我们对它们在应激诱导的缺陷中的作用了解很少 灭绝学习。在这个提议中，我们研究了星形胶质细胞(最主要的 神经胶质细胞群)影响应激诱导的消亡学习障碍。更具体地说，我们研究 大脑边缘下部前额叶皮质星形胶质细胞之间的关系 学习和压力导致的消退性学习缺陷。我们假设，在成年人的大脑中，压力- 在灭绝学习中诱导的缺陷，部分是由应激激素作用和增加的神经元活性调节的。 发育信号通路，在下缘前额叶皮质的星形胶质细胞。为了检验这一假设， 我们将在操纵压力激素受体功能后，研究压力导致的消亡学习缺陷。 而发育信号的活动在下缘前额叶皮质的星形胶质细胞中级联。 我们工作的成功结果将为星形胶质细胞的分子功能如何有助于 应激导致的消亡学习障碍。此外，我们的工作有可能推荐新的 细胞类型的特定分子通路，可靶向减轻高度流行和衰弱的 创伤后应激障碍的记忆相关维度。

PROJECT SUMMARY Post Traumatic Stress Disorder (PTSD) is a devastating neuropsychiatric disorder that develops after trauma. A previous history of stress exposure significantly increases the likelihood of developing PTSD after a traumatic event. Deficits in extinction learning are a debilitating and core symptom of PTSD. This inability to learn that stimuli previously linked to trauma are no longer threatening causes maladaptive fear expression toward these stimuli. Efforts to reduce stress-induced deficits in extinction learning have included identifying stress-induced perturbations of molecular pathways in the brain. Most of this work has either treated brain regions as a homogeneous population of cells or mainly focused on neurons. While glia are the most populous cells in the nervous system, we have little appreciation for their contribution to stress-induced deficits in extinction learning. In this proposal, we examine how molecular events in astrocytes (the most predominant glial cell population) influence stress-induced deficits in extinction learning. More specifically, we study the relationship between astrocytes in the infra-limbic prefrontal cortex, a brain region important for extinction learning and stress-induced deficits in extinction learning. We hypothesize that in the adult brain, stress- induced deficits in extinction learning are, in part, mediated by stress hormone action and increased activity of developmental signaling pathways, in astrocytes of the infra-limbic prefrontal cortex. To test this hypothesis, we will study stress-induced deficits in extinction learning after manipulating stress hormone receptor function and the activity of developmental signaling cascades in astrocytes of the infra-limbic prefrontal cortex. Successful outcomes from our work will shed new light on how molecular function in astrocytes contribute to stress-induced impairments in extinction learning. Additionally, our work has the potential to recommend new cell-type specific molecular pathways that could be targeted to mitigate a highly prevalent and debilitating memory-related dimension of PTSD.