INVESTIGATING HOW NOVELTY ENHANCES FEAR LEARNING & MEMORY

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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.