INVESTIGATING HOW NOVELTY ENHANCES FEAR LEARNING & MEMORY

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.

Grant Number: 1R15MH129947-01A1
NIH Institute/Center: NIH
Principal Investigator: Victor Cazares