Neural circuits of platform avoidance

描述（由申请人提供）：PTSD的常见症状包括恐慌发作和持续回避与创伤相关的刺激。为了了解恐慌的潜在机制，研究人员在啮齿动物中使用了巴甫洛夫恐惧条件反射模型。与恐惧条件反射相反，人们对回避回路知之甚少。持续的回避会通过干扰目标达成和奖励（成本）严重降低患者的生活质量。在这个提议中，我们将研究大鼠回避的神经机制，使用平台回避任务，在该任务中，暴露于与电击配对的音调的大鼠可以通过踏上平台来避免电击。由于平台位于远离食物栏，避免剥夺大鼠获得食物（成本），从而模拟临床避免的一个重要方面。在目标1中，我们将测试前额叶次区域前边缘和边缘下皮层是否是必要的回避。我们还将测试杏仁核和纹状体，这是前额叶的目标，是否也是平台回避的关键。在目标2中，我们将描述前边缘系统和纹状体神经元在回避表达过程中的反应，以及纹状体中的回避反应在多大程度上取决于前边缘系统的输入。了解主动回避的神经回路将有助于指导PTSD中持续回避的治疗。

DESCRIPTION (provided by applicant): Common symptoms of PTSD include panic attacks and persistent avoidance of stimuli associated with the trauma. To understand the underlying mechanisms of panic, researchers have used the model of Pavlovian fear conditioning in rodents. In contrast to fear conditioning, little is known about the circuits of avoidance. Persistent avoidance can severely decrease patients' quality of life by interfering with goal- attainment and reward (cost). In this proposal, we will investigate the neural mechanisms of avoidance in rats, using a platform avoidance task, in which rats exposed to a tone paired with a shock can avoid the shock by stepping onto a platform. Because the platform is located away from the food bar, avoidance deprives rats of access to food (cost), thereby modeling an important aspect of clinical avoidance. In Aim 1, we will test whether the prefrontal subregions prelimbic and infralimbic cortex are necessary for avoidance. We will also test whether the amygdala and striatum, which are prefrontal targets, are also critical for platform avoidance. In Aim 2, we will characterize the responses of prelimbic and striatal neurons during expression of avoidance, and the extent to which avoidance responses in striatum depend upon prelimbic input. Understanding the neural circuits of active avoidance will help guide treatment for persistent avoidance in PTSD.