Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

Stafford, James M.; Maughan, Dee Anna K.; Ilioi, Elena C.; Lattal, K. Matthew

doi:10.1101/lm.029801.112

Cited by 44 publications

(47 citation statements)

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“…Schiller et al (2010) translated this procedure to humans; perhaps the most amazing finding of that study was that humans given a single retrieval trial 10 min prior to extinction showed no reinstatement of fear even when tested 1 yr later. However, there are several reports where extinction learning after retrieval did not prevent the recovery of fear in adult humans (Golkar et al 2012;Kindt and Soeter 2013) and adult mice (Stafford et al 2013), and even increased the recovery of fear in adult rats (Chan et al 2010).…”

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confidence: 94%

Memory retrieval before or after extinction reduces recovery of fear in adolescent rats

2013

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Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a retrieval -extinction procedure would reduce the recovery of extinguished fear in adolescent rats. Furthermore, the effect of the retrievalextinction sequence on fear recovery was examined by presenting the retrieval trial following extinction to some animals. In Experiment 1 adolescent rats received one nonreinforced CS presentation (a retrieval trial) or equivalent context exposure (no retrieval) 10 min before fear extinction. A retrieval trial shortly before extinction reduced overall levels of fear in both test contexts (i.e., it improved extinction retention and reduced renewal). In Experiment 2 a weakening of renewal was observed with a retrieval -extinction manipulation, regardless of whether the retrieval trial occurred in the training or extinction context. A key result was that a retrieval trial 10 min, but not 6 h, after extinction led to reduced overall levels of fear similar to that observed if the retrieval trial was given before extinction (Experiments 3 and 4), inconsistent with the current interpretation of the reduction in relapse being due to a disruption of reconsolidation. Together, these findings show that the impaired extinction retention observed in adolescents can be ameliorated by a very simple behavioral manipulation, but also raise some questions about the mechanisms underlying the retrieval-extinction effect.

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confidence: 94%

Memory retrieval before or after extinction reduces recovery of fear in adolescent rats

2013

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“…Pavlov (1927) was the first to suggest that recently formed associations should be more readily extinguished. Consistent with this prediction, there is evidence that fear memories in a labile state due to recent acquisition (Myers et al 2006) or recent retrieval (Monfils et al 2009;Schiller et al 2010) are especially susceptible to extinction, although the literature regarding these phenomena is mixed (Chan et al 2010;Stafford et al 2013; for review, see Maren 2014). To our knowledge, the effect on fear conditioning of variation in the amount of postshock context exposure within the same session as acquisition has not been investigated parametrically (but see Kiernan et al 1995;Lattal and Abel 2001).…”

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confidence: 61%

“…An initial study by Myers et al (2006) using fearpotentiated startle reported that extinction within a few minutes after acquisition (immediate extinction) caused a more durable suppression of the conditioned response than did extinction 24 h after acquisition. However, subsequent studies using aversive (Maren and Chang 2006;Woods and Bouton 2008;Chang and Maren 2009;Archbold et al 2010;Stafford et al 2013) and appetitive procedures (Rescorla 2004;Woods and Bouton 2008) in rodents as well as humans (Norrholm et al 2008;Schiller et al 2008) failed to observe superiority of immediate extinction. Indeed, in a number of studies immediate extinction was less effective than delayed extinction at suppressing the CR (Rescorla 2004;Maren and Chang 2006;Woods and Bouton 2008;Chang and Maren 2009;Stafford et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In the earlier fear conditioning studies that failed to observe immediate extinction superiority, the level of fear exhibited during immediate extinction was as high or higher than that displayed during delayed extinction, because most studies used stronger conditioning procedures involving multiple shocks (one exception is Stafford et al 2013). In contrast, in our single-shock CFC paradigm, mice displayed very low levels of freezing during the immediate postshock period.…”

Section: Discussionmentioning

confidence: 99%

“…It is well established that cued and context fear conditioning recruit distinct neural mechanisms (Kim and Fanselow 1992;Phillips and LeDoux 1992;Maren et al 1997), raising the possibility that cued and context conditioning are differentially sensitive to immediate extinction. However, two recent studies (Archbold et al 2010;Stafford et al 2013) compared the effectiveness of immediate and delayed extinction of context fear and failed to observe superiority of immediate extinction. Thus, the use of contextual versus discrete-cue conditioning does not explain the differences between our findings and those studies failing to observe immediate extinction superiority.…”

Section: Discussionmentioning

confidence: 99%

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Potent attenuation of context fear by extinction training contiguous with acquisition

Bernier

Lacagnina

Drew³

2014

Learn. Mem.

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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...

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Minimizing Variability in Developmental Fear Studies in Mice: Toward Improved Replicability in the Field

Premachandran,

Wilkin,

Arruda‐Carvalho

2024

Current Protocols

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In rodents, the first weeks of postnatal life feature remarkable changes in fear memory acquisition, retention, extinction, and discrimination. Early development is also marked by profound changes in brain circuits underlying fear memory processing, with heightened sensitivity to environmental influences and stress, providing a powerful model to study the intersection between brain structure, function, and the impacts of stress. Nevertheless, difficulties related to breeding and housing young rodents, preweaning manipulations, and potential increased variability within that population pose considerable challenges to developmental fear research. Here we discuss several factors that may promote variability in studies examining fear conditioning in young rodents and provide recommendations to increase replicability. We focus primarily on experimental conditions, design, and analysis of rodent fear data, with an emphasis on mouse studies. The convergence of anatomical, synaptic, physiological, and behavioral changes during early life may increase variability, but careful practice and transparency in reporting may improve rigor and consensus in the field. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

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Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuits

Cited by 44 publications

References 51 publications

Memory retrieval before or after extinction reduces recovery of fear in adolescent rats

Memory retrieval before or after extinction reduces recovery of fear in adolescent rats

Potent attenuation of context fear by extinction training contiguous with acquisition

Minimizing Variability in Developmental Fear Studies in Mice: Toward Improved Replicability in the Field

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