Extinction of Recent Fear: Behavioral and Neural Mechanisms.

Abstract

Fear is an evolutionarily conserved emotion that helps organisms respond to current danger and avoid future threats. However, in some individuals, a fearful experience yields persistent psychological disturbances. Early intervention (e.g., debriefing) following trauma is suggested to be an effective strategy for limiting subsequent psychopathology. In animals, therapeutic interventions for fear can be modeled using extinction procedures, in which a stimulus that has been associated with an aversive event is presented alone many times. Interestingly, there has been no systematic study of the effectiveness of extinction given shortly after a traumatic experience. Here, we examined this issue in rats by comparing the magnitude of extinction generated by delivering extinction trials either 15 min or 24 hours after auditory fear conditioning, a form of learning in which an acoustic tone is paired with an aversive footshock. We hypothesized that immediate extinction would produce fear suppression and impair the consolidation of long-term fear memory. Contrary to our hypothesis, immediate extinction produced minimal fear suppression assessed twenty-four hours after training, and this deficit was related to sensitized fear prior to extinction. Although immediate extinction failed to produce long-term fear suppression, it did produce a short-term suppression that exhibited properties of habituation. We next examined the neural substrates of the immediate extinction deficit. We focused on the medial prefrontal cortex, a brain structure involved in extinction learning and consolidation. Using electrophysiological recording and pharmacological manipulations, we found that that the immediate extinction deficit was due to dysfunction of the infralimbic division (IL) of the medial prefrontal cortex. Moreover, the deficit could be rescued by pharmacological manipulations that facilitate the IL function. Taken together, these results suggest that the IL is important for the acquisition of long-term extinction, and that recent fear suppresses IL function leading to an immediate extinction deficit. These data suggest early interventions for trauma in humans may not be optimal, particularly if the acute stress associated with trauma is extreme. Pharmacological interventions that manage acute stress and augment prefrontal cortical function may improve the efficacy of extinction, increase long-term fear reduction, and limit the incidence of anxiety disorders.