Postextinction of conditioned fear: between two CS-related memories.

In his classical studies, Pavlov (1927) demonstrated that when a neutral stimulus is frequently paired with an event (unconditioned stimulus: US), which always produces innate or unconditioned responses, it becomes capable (conditioned stimulus: CS) of eliciting learned or conditioned responses. Conditioned responses typically have adaptive functions. However, conditioning of certain states, such as fear, can also be nonproductive. Fortunately, both animals and humans can exhibit opposing central mechanisms that weaken the strength of conditioned responses in certain conditions. For example, if after conditioning (CS–US pairing), the CS is repeatedly presented without the US, the strength of the conditioned response diminishes progressively over time. According to Pavlov (1927), this process, which he termed extinction, occurs as the result of the activation of a central inhibitory state that prevents the expression of conditioned responses. He also demonstrated that the engagement of this inhibitory state declines with the passage of time, a phenomenon known as spontaneous recovery (Pavlov 1927). This observation is not only true in appetitive conditioning (Pavlov’s studies; Bouton 1993; Brooks and Bouton 1993), but has also been validated in aversive conditioning (Brooks et al. 1999). In this issue of Learning & Memory, Quirk (2002) investigates several questions pertaining to the persistence of extinction memory and the development of spontaneous recovery and presents results indicating that conditioning and extinction of cued fear conditioning are mediated by independent systems. Studies on postextinction effects of CS, particularly the phenomenon of spontaneous recovery, have fundamentally contributed to the understanding of certain aspects of the nature of extinction. For example, these studies indicate that extinction does not erase memory of conditioning (see Fig. 1). Thus, conditioning and extinction result from the formation of distinct CS-related memories that are separately accessible after the extinction period (Falls et al. 1992; Bouton 1993; Rescorla 2001; Santini et al. 2001). However, it remains unclear whether the extinction memory trace progressively fades with the passage of time or whether this memory persists despite spontaneous recovery. To examine these issues, Quirk (2002) measured spontaneous recovery at various time points up to 14 d. Rats were previously conditioned to express freezing response toward a tone following tone–footshock (CS–US) pairings and then exposed to the CS-alone presentations for extinction of the conditioned fear, which was characterized by a progressive reduction of conditioned freezing to negligible levels. Remarkably, when rats were reexposed to the CSalone, they started displaying, from days 1–2, low levels of fear return (spontaneous recovery), which increased as a function of retention interval reaching 100% of preextinction values by day 10. Data from control rats, submitted to conditioning but not to extinction, showed that the passage of time alone did not increase the expression of conditioned freezing. Thus, the observed progressive spontaneous recovery was likely due to reduced activation of extinction memory rather than to increased activation of conditioning memory. The finding opens up the possibility that extinction memory is a short-lasting phenomenon that fades completely when long delays elapse between extinction and testing. Quirk also examined this possibility by resubmitting rats to extinction at day 14. Although all rats exhibit a full return of conditioned fear on day 14, they significantly reextinguished this fear faster than they did during the initial extinction, suggesting savings from the initial learning training (initial postconditioning CS-alone presentations). If, following extinction, both forms of memory (extinction and conditioning memories) are simultaneously accessible, which factors preferentially activate one or the other type of memory during further exposure to the CS? Environmental cues have been suggested to play a key role. Bouton (1993) has suggested that the passage of time may produce temporal context changes, which may, in turn, incur a failure to retrieve the extinction memory. In this condition the perception of the CS automatically activates the CS–US memory (signaling a possible occurrence of the US); the outcome being stronger conditioned responses. In Quirk’s study, because conditioning and extinction took place in the same context, it may be possible that with longer retention intervals the CS preferentially activated the CS–US memory rather than the CS–no-US memory. However, if such conditioning (i.e., tone–footshock pairings) E-MAIL rene.garcia@unice.fr; FAX (33)-4-9207-6162. Article and publication are at http://www.learnmem. org/cgi/doi/ 10.1101/lm.56402.