Gene regulation during memory storage provides insight into the cognitive role of neural circuits

Memories occur as a result of experience and can affect behavior. I investigated the biological correlates of memory storage by focusing on gene regulation following classical conditioning for contextual fear in mice. This model task requires configural representation of a novel environment and association of the environment with an aversive stimulus, footshock. The time course of memory storage can be well-defined for this task, because learning occurs following a single training session. While previous reports had identified many genes that are regulated in the hippocampus following fear conditioning, I expanded this list and additionally identified genes regulated in the amygdala. I found that while gene regulation was predominantly driven by the novel context exposure, the amygdala demonstrated additional regulation in response to associative learning. Computational methods were used to generate hypotheses regarding the molecular circuitry regulating these events. Because previous studies implicated the transcription factors CREB and Elk-1 in regulating genes during memory storage, I created a method to detect signaling events that activate these transcription factors using reporter genes. The reporter system I created had the additional benefit of being controllable because it utilized the tetracycline-sensitive DNA binding activity of the bacterial TetR gene. Although I was unable to demonstrate this system in transgenic mice, recent methods have demonstrated the utility of treating gene regulation as an intrinsic signal of neural activity. Therefore, the results of my study could provide vital information for future investigation of brain-region specific activity during memory storage