PREFRONTAL AMYGDALA INTERACTIONS IN FEAR CONDITIONING

描述（改编自申请人摘要）：研究 近年来，随着对恐惧的研究，情绪的神经生物学已经取得了进展 条件化中性刺激（条件化刺激，CS）变成 与厌恶事件（无条件刺激，US）相关， 随后暴露于CS引起生理和行为恐惧 应答 在没有US的情况下重复展示CS导致 恐惧反应的减弱，这一过程被称为灭绝。 未能 消除恐惧反应可能形成焦虑症的基础， 恐惧症和创伤后应激障碍 而大脑的神经回路 恐惧条件反射的获得正变得越来越好理解， 灭绝的电路相对未知。 杏仁核对于 恐惧条件反射 大脑皮层对杏仁核的输入， 恐惧条件反射可以调节恐惧行为。 最近的数据显示， 内侧前额叶皮质（mPFC）和杏仁核基底外侧核 (BLA)，它们相互连接，可以形成神经回路的一部分， 灭绝 三个实验将检验这一核心假设。 1. 大鼠 mPFC损伤的患者将接受bar的条件性抑制训练 压迫，然后消退和恢复（假设：大鼠 没有mPFC将获得，但不会消除恐惧反应）。 2. 河豚属 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神经元将表现出衰减诱导的音调反应变化， 细胞与细胞之间的相关性在采集过程中没有发生，这表明 mPFC在灭绝期间学习新的CS-US关联中的作用）。 3. 在麻醉大鼠中，在BL神经元记录的同时刺激mPFC （假设：mPFC导致BLA的前向摄食抑制）。 第四 河豚属 将用于记录动物在恐惧条件反射期间BLA神经元的活动 有和没有完整的mPFC（假设：来自对照动物的BLA细胞 将显示快速消退的条件音反应，而BLA细胞 从病变动物将更缓慢地熄灭）。 这项研究将 推进我们对大脑恐惧处理的理解。 特别是， 它将开始告诉我们什么电路对灭绝很重要， 熄灭的刺激与非熄灭的刺激的表现方式不同 刺激小的神经元群体。 最终，它将导致更多 有效的治疗焦虑症，因为我们的理解， 恐惧的神经机制增强。

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.