Out-of-Context Activation of Memory: Limits of Stress-Induced Memory Enhancement

Abstract

Posttraumatic stress disorder (PTSD) can be a sequela of a traumatic event that elicits an extremely fearful reaction, and is accompanied by re-experiencing of the trauma, numbing or avoidance behavior, and persistent hyperarousal. A signature feature of PTSD is the recurrent, involuntary, and intrusive recollection of a traumatic memory, colloquially referred to as flashbacks, which occur outside of the original experience. Whether an aberrant stress response is a contributing factor to eliciting these intrusive memories, our rodent studies suggest that the response to a stressful experience can activate previously acquired memories in a context that is unrelated to the original learning situation. This observation, which we call 'out-of-context activation of memory' (OCAM), may be a useful model with which to study how an extreme stress response can influence unrelated memories, and that the subsequent modification of these unrelated memories may interfere with normal functioning and contribute to the behavioral alterations and disturbances that characterize disorders such as PTSD. Our previous work reported that after a swim-stress experience, the expression of an unrelated memory was enhanced. The learning environment and the swim environment had no physically identifiable common feature, and yet swim-stress, conducted one day after learning a left/right (L/R) discrimination task, enhanced the subsequent recall of the L/R discrimination task. In addition, swim-stress induced a stable memory to become susceptible to amnestic treatments such as propranolol and electro-convulsive shock. Taken together, this evidence suggests that the stress response to an adverse situation can modify stable, unrelated memories. The goal of my work was to evaluate and characterize the limitations of a stress-induced modification of stable, unrelated memories. There four main findings: (1) the level of physiological stress was not a common feature between the learning and swim-stress experience, (2) corticosteroids play a necessary but not sufficient role in enhancing the expression of a stable, unrelated memory, (3) swim-stress can enhance the expression of a stable, unrelated memory within a time-limited window of up to at least one week after learning, and (4) swim-stress does not enhance memories that are dependent on the hippocampus for its expression.