INVESTIGATING HOW NOVELTY ENHANCES FEAR LEARNING & MEMORY

项目摘要 我们将研究一种具有高度特征性的学习形式，恐惧消亡(FE)，这是已知的几种 创伤和焦虑相关障碍的不适应表型。暴露疗法在很大程度上是基于恐惧 FE，在此期间，个体在缺乏恐惧的情况下反复暴露于恐惧条件刺激 令人厌恶的结果，导致恐惧反应逐渐减少。FE训练被认为创造了一个新的 抑制习得的恐惧反应的记忆。先前的研究表明，神经元的激活 编码FE记忆随着时间的推移迅速减弱，导致糟糕的FE回忆和恐惧的回归。我们和 其他人则发现，接触新奇事物会增强自学能力。在这项建议中，我们寻求：(1)确定 新颖性促进FE学习的具体参数；(2)询问 海马体调节新奇事物的FE增强效应；以及(3)映射神经激活模式 在FE期间，在存在或不存在新颖性的情况下进行更改。最后，考虑到 在人类对暴露治疗的反应性方面，我们将调查遗传背景在 塑造FE疗效和神经激活之间的功能关系。

Project Summary We will study a highly characterized forms of learning, fear extinction (FE), which is known to underlie several maladaptive phenotypes in trauma- and anxiety-related disorders. Exposure therapy is largely based on fear FE, during which individuals are repeatedly exposed to a fear-conditioned stimulus in the absence of the aversive outcome, leading to a gradual decrease in the fear response. FE training is believed to create a new memory that inhibits learned fear responses. Previous research suggests that the activation of neurons encoding FE memories rapidly wanes over time, resulting in poor FE recall and the return of fear. We and others have found that exposure to novelty enhances FE learning. In this proposal we seek: (1) to determine the specific parameters under which novelty enhances FE learning; (2) to interrogate the role of the hippocampus modulating the FE-enhancing effects of novelty; and (3) to map how neural activation patterns are altered in the presence or absence of novelty during FE. Finally, given the high individual variation in the responsiveness to exposure therapy among humans, we will investigate the role of genetic background in shaping functional relationships between the efficacy of FE and neural activation.