Neural circuits of platform avoidance

描述（由申请人提供）：PTSD的常见症状包括惊恐发作和持续回避与创伤相关的刺激。为了理解恐慌的潜在机制，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。与恐惧条件反射相比，人们对回避回路知之甚少。持续的回避会干扰目标的实现和回报（成本），从而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，在这个任务中，大鼠暴露在与电击搭配的音调中，可以通过走上平台来避免电击。由于平台远离食物栏，回避剥夺了大鼠获得食物的机会（成本），从而模拟了临床回避的一个重要方面。在目的1中，我们将测试前额叶亚区，前边缘和边缘下皮层是否对回避是必要的。我们还将测试作为前额叶目标的杏仁核和纹状体是否也对平台回避至关重要。在目标2中，我们将描述回避表达过程中边缘前和纹状体神经元的反应，以及纹状体中回避反应依赖于边缘前输入的程度。了解主动回避的神经回路将有助于指导PTSD持续性回避的治疗。

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.