Potent attenuation of context fear by extinction training contiguous with acquisition

Abstract

Studies on the behavioral mechanisms underlying contextual fear conditioning (CFC) have demonstrated the importance of preshock context exposure in the formation of aversive context memories. However, there has been comparatively little investigation of the effects of context exposure immediately after the shock. Some models predict that nonreinforced context exposure at the end of the acquisition session will strongly influence the strength of conditioning and/or recruit distinct neural mechanisms relative to extinction after acquisition. Here we investigate the effects of manipulating postshock context exposure on CFC in mice. Prolonging the period of context exposure immediately following the shock caused a significant and durable reduction in conditioned fear. This immediate postshock context exposure was more effective at attenuating conditioned fear than was an equivalent amount of context exposure a day or more after acquisition. The results suggest that nonreinforced exposure to the context influences conditioned fear through distinct mechanisms depending on whether it occurs during acquisition or after it. The superiority of immediate postshock context exposure was specific to single-shock CFC; in two-shock CFC, immediate and delayed postshock context exposure had similar effects. Consistent with previous reports, we hypothesize that the effectiveness of extinction is modulated by emotional state, and procedures engendering higher postshock freezing (such as two-shock CFC) are associated with weaker immediate extinction.Contextual fear conditioning (CFC) is a form of associative learning that occurs when an aversive experience, usually a footshock in laboratory experiments, occurs within a distinctive place or context. Learned contextual fear typically recruits plasticity in the hippocampus, which is thought to generate a conjunctive mnemonic representation of stimuli present during the learning episode (Rudy et al. 2004;Fanselow 2010). The robustness of this form of learning has made it one of the preferred methods for studying mechanisms of hippocampus-dependent memory and learned fear.While the neural mechanisms of CFC have been researched extensively, there has been comparatively little investigation of the behavioral mechanisms through which the emotional valence of a context is established. One longstanding idea is that the strength of context conditioning is determined by the overall rate of unconditioned stimulus (US) presentation per unit time in the context (Rescorla and Wagner 1972;Gibbon and Balsam 1981). This approach accounts for the observation that increasing the intertrial interval in conditioning experiments tends to decrease the amount of conditioned responding elicited by the context (Fanselow et al. 1993;Barela 1999). However, this model fails to account for a key property of CFC: very brief preshock context exposure leads to an absence of context fear, rather than robust fear as the rate-based model would predict (Fanselow 1986). This phenomenon, known as the immediate shock defici...

A cFos activation map of remote fear memory attenuation

“…In the “Context Only” group, we observed a slight increase in freezing between the first and the last exposure to the context (Fig. 1d, repeated measures ANOVA, F (1.7, 18) = 3.11, P = 0.075, n = 12), which could stem from incremental immobility deriving from a lack of exploratory drive to an already familiar context (Bernier et al 2015, 2017).…”

Know safety, no fear

“…There is some evidence that more extensive extinction training involves depotentiation, which yields a more permanent suppression of learned fear 129 . Similarly, behavioral and pharmacological interventions such as retrieval-extinction 130 , immediate extinction 131,132 , pharmacological blockade of reconsolidation 133,134 , and epigenetic manipulations 135 may more effectively suppress fear than traditional extinction training. However, many questions remain about the generality, effectiveness, and mechanisms of these procedures (for review see 136 ).…”

Behavioral mechanisms of context fear generalization in mice

“…The training protocol for three-shock foreground (uncued) CFC was identical to the three-shock background CFC protocol, except tones were not presented. In one-shock foreground CFC, training consisted of a single shock (2 sec, 0.75 mA) occurring 180 sec into the 212-sec session (Wiltgen et al 2001;Drew et al 2010;Bernier et al 2014).…”