PREFRONTAL AMYGDALA INTERACTIONS IN FEAR CONDITIONING

描述(改编自申请者的摘要)：研究 近年来，随着对恐惧的研究，情绪的神经生物学取得了进展 条件化的中性刺激(条件化刺激，CS)变成 与令人厌恶的事件(无条件刺激，美国)有关 随后暴露于CS会引起生理和行为上的恐惧 回应。在没有美国的情况下反复提交政务司司长报告导致了 恐惧反应减弱，这一过程被称为消亡。未能做到 消除恐惧反应可能形成焦虑症的基础，如 恐惧症和创伤后应激障碍。而神经回路则是 恐惧条件反射的习得正变得越来越清楚， 物种灭绝的电路相对来说是未知的。杏仁核对于 恐惧条件反射。杏仁核的皮质输入，而不是必需的 恐惧条件作用可能会调节恐惧行为。最近的数据表明， 内侧前额叶皮质和杏仁基底外侧核 (BLA)，它们是相互连接的，可能形成了 灭绝。三个实验将验证这一中心假设。1.老鼠 对有病变的mPFC进行条件性抑制训练 按压，然后灭绝和恢复(假设：大鼠 如果没有mpfc，恐惧反应将会产生，但不会消失)。2.四极管 将用于记录行为大鼠的多个mPFC神经元 经历恐惧条件反射的获得和消退(假设： MPFC神经元将表现出消退引起的音调反应和 在获取过程中没有发生的细胞-细胞相关性，表明 MPFC在学习灭绝期间新的CS-US协会中的作用)。3. 麻醉大鼠记录下丘脑前部神经元时刺激mPFC (假设：mPFC导致对BLA的饲料前向抑制)。和，4.四足动物 将被用来记录动物在恐惧条件反射过程中的BLA神经元 有和没有完整的mPFC(假设：来自对照动物的BLA细胞 会表现出条件音反应的快速消退，而BLA细胞 从病变中，动物会更慢地熄灭)。这项研究将 提高我们对大脑中恐惧处理的理解。特别是， 它将开始告诉我们哪些电路对物种灭绝是重要的，以及它们是如何 已熄灭的刺激与未熄灭的刺激的表示方式不同 一小群神经元中的刺激。最终，它将带来更多 焦虑症的有效治疗，正如我们对 恐惧的神经机制增加。

DESCRIPTION (Adapted from applicant's abstract): Research into the neurobiology of emotion has advanced in recent years with studies of fear conditioning a neutral stimulus (the conditioned stimulus, CS) becomes associated with an aversive event (the unconditioned stimulus, US) so that subsequent exposure to the CS evokes physiological and behavioral fear responses. Repeated presentation of the CS without the US leads to a diminution of fear responses, a process known as extinction. Failure to extinguish fear responses may form the basis of anxiety disorders such as phobias and post traumatic stress disorder. While the neural circuitry for the acquisition of fear conditioning is becoming well understood, the circuitry of extinction is relatively unknown. The amygdala is crucial for fear conditioning. Cortical inputs to the amygdala, while not required for fear conditioning may modulate fear behavior. Recent data suggest that the medial prefrontal cortex (mPFC) and the basolateral nucleus of the amygdala (BLA), which are interconnected, may form part of the neural circuitry of extinction. Three experiments will test this central hypothesis. 1. Rats with lesions of the mPFC will be trained in conditioned suppression of bar pressing, followed by extinction and reinstatement (hypothesis: rats without mPFC will acquire, but not extinguish fear responses). 2. Tetrodes will be used to record from multiple mPFC neurons in behaving rats undergoing acquisition and extinction of fear conditioning (hypothesis: mPFC neurons will show extinction induced changes in tone responses and cell-cell correlations that did not occur during acquisition, suggesting a role of mPFC in learning new CS-US associations during extinction). 3. mPFC will be stimulated in anesthetized rats while recording from BL neurons (hypothesis: mPFC causes feed foward inhibition of BLA). And, 4. Tetrodes will be used to record from BLA neurons during fear conditioning, in animals with and without an intact mPFC (hypothesis: BLA cells from control animals will show rapid extinction of conditioned tone responses, while BLA cells from lesions animals will extinguish more slowly). This research will advance our understanding of fear processing in the brain. In particular, it will begin to tell us what circuits are important for extinction, and how extinguished stimuli are represented differently from non-extinguished stimuli in small groups of neurons. Ultimately, it will lead to more effective treatments for anxiety disorders, as our understanding of the neural mechanisms of fear increases.