Prefrontal amygdala interactions in fear conditioning

追求奖励和回避威胁是两种主要的行为动机。无法平衡这些 动机导致不适应的决定，并可能成为各种病理状况的基础。的 NIMH研究领域标准（RDoC）的持续威胁结构包括避免、冲突 检测和持续行为。持续的威胁反应干扰了对奖励的追求 减少社交互动并引发抑郁症的活动。人们对决策是如何 在接近-回避冲突中引导行为。MERIT的第一阶段将我们的重点从 巴甫洛夫恐惧条件反射到主动回避，探索前额叶-杏仁核-纹状体回路如何表达 并消除主动回避。在第二个MERIT阶段，我们制定了一项新任务， 最大限度地接近回避冲突内的定时提示遇到坑主动回避对 追求食物。新的接近-回避冲突任务揭示了三种不同的行为 表型：1）偏好食物的大鼠，在整个音调中几乎不回避或不回避地追求食物; 2） 回避偏好大鼠，其在整个音调中回避，很少或不寻找食物;和3）定时器， 及早寻找食物，避免晚些时候，从而最大限度地获得食物和安全。我们将 利用这些独特的行为表型来表征电路介导的方法- 回避决策，使用电生理学，免疫组织化学和光遗传学方法。我们将 在我们所有的目标中都使用雄性和雌性老鼠。目的1将免疫组化结合 电生理学和纤维光度学来识别参与冲突决策的电路。目标2将 用光遗传学操作测试目标1中确定的电路。目标3将评估这项任务的威力 识别新的多维行为表型，将冲突策略与焦虑相结合， 社交互动这项研究计划将使我们能够表征决策电路的基础 不同的策略来解决接近-回避冲突。 相关性（参见说明）： 如果不能在追求奖励和避免威胁之间取得平衡，就会导致适应不良的决定， 包括焦虑和抑郁的病理状况。使用一种新的啮齿动物任务， 接近-回避冲突，我们将描述电路调解接近-回避决策 使用电生理学、免疫组织化学和光遗传学方法。这项研究计划将 使我们能够表征解决接近-回避冲突的电路。

Pursuit of reward and avoidance of threat are two major behavioral motivators. Failure to balance these motivations results in maladaptive decisions and may underlie various pathological conditions. The sustained threat construct of the NIMH Research Domain Criteria (RDoC) includes avoidance, conflict detection, and perseverative behaviors. Sustained threat reactions interfere with the pursuit of rewarding activities that can decrease social interactions and trigger depression. Little is known about how decisions guide behavior during approach-avoidance conflict. The first phase of this MERIT shifted our focus from Pavlovian fear conditioning to active avoidance, exploring how prefrontal-amygdala-striatal circuits express and extinguish active avoidance. For the second MERIT phase, we have developed a new task that maximizes approach-avoidance conflict within a timed cue encounter that pits active avoidance against the pursuit of food. The new approach-avoidance conflict task has revealed three distinct behavioral phenotypes: 1) food-preferring rats that pursue food throughout the tone with little or no avoidance; 2) avoidance-preferring rats which avoid throughout the tone with little or no food-seeking; and 3) timers which seek food early in the tone and avoid later, thereby maximizing both access to food and safety. We will capitalize on these unique behavioral phenotypes to characterize the circuits mediating approach- avoidance decisions, using electrophysiological, immunohistochemical, and optogenetic methods. We will use both male and female rats in all our aims. Aim 1 will use immunohistochemistry combined with electrophysiology and fiber photometry to identify the circuits involved in conflict decision making. Aim 2 will test the circuits identified in Aim 1 with optogenetic manipulations. Aim 3 will assess the power of this task to identify new multi-dimensional behavioral phenotypes integrating conflict strategies with anxiety and social interactions. This research program will enable us to characterize decision-making circuits underlying different strategies for resolving approach-avoidance conflict. RELEVANCE (See instructions): Failure to balance pursuit of reward and avoidance of threat results in maladaptive decisions and pathological conditions including anxiety and depression. Using a novel rodent task that maximizes approach-avoidance conflict, we will characterize the circuits mediating approach-avoidance decisions using electrophysiological, immunohistochemical, and optogenetic methods. This research program will enable us to characterize circuits for resolving approach-avoidance conflict.