Acuqisition, extinction, and spontaneous recovery of fear conditioning for neural mechanisms

Abstract

Whether rats exposed to the same context without footshock after context-footshock conditioning retain or forget the fear memory remains debatable. Elucidating the brain areas involved in fear conditioning, its extinction, and spontaneous recovery may reveal answers. The present study utilized a passive avoidance learning paradigm to test for the interference versus unlearning/forgetting hypothesis. Rats were subjected to three sessions of context/footshock (0.5 mA, 2 s) pairings followed by 12 extinction sessions (context-no footshock). After the last extinction test, rats were assigned to one of three groups, with the group assignments reflecting the timing of the test session (context-no footshock): Day 8, Day 9, and Day 10. Only the Day 10 group exhibited spontaneous recovery during the test session. The acquisition of fear affected c-fos expression in the amygdala and cingulate cortex areas 1 (Cg1). The extinction of fear affected c-fos expression in the Cg1, cingulate cortex 2 (Cg2), piriform cortex (Pir), and entorhinal cortex (Ect). Spontaneous recovery affected c-fos expression in the amygdala, Pir, and Ect. In conclusion, conditioned fear effect recovered since rather longer testing time on the same context. It was suggested once new context-no footshock learning became weaker than context-footshock learning; supporting the interference hypothesis. Our results suggest that competition between long-term potentiation and long-term depression may be involved in extinction and spontaneous recovery. The implication of the present findings may be useful for the clinical understanding and prevention of spontaneous relapse for phobias, anxiety disorders, and posttraumatic stress disorder. ? Keywords: fear conditioning, extinction, spontaneous recovery, interference hypothesis, unlearning hypothesis