Extinguished second-order conditioned fear responses are renewed but not reinstated.

Holmes, Nathan M.; Cai, Stefanie Yuxuan; Lay, Belinda P. P.; Watts, Nicola; Westbrook, R. Frederick

doi:10.1037/xan0000036

Cited by 19 publications

(19 citation statements)

References 33 publications

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“…However, one limitation of our study is the observation of higher freezing levels during the habituation phase of the extinction retrieval compared to the habituation phase of the extinction training. This might be explained by second-order conditioning to the context and exclusively occurs following a weak extinction protocol, which limits already the efficacy of the extinction (Holmes et al 2014;Lay et al 2018;Rizley & Rescorla 1972).…”

Section: Discussionmentioning

confidence: 99%

Effects of ghrelin receptor activation on forebrain dopamine release, conditioned fear and fear extinction in C57BL/6J mice

Pierre

Schuerbeek

Allaoui

et al. 2020

Journal of Neurochemistry

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The ghrelin system was previously proposed to mediate an independent branch of the stress response that curbs fear processing. Interestingly, the ghrelin system was also shown to control the activity of midbrain dopamine neurons. Given that dopamine neurons of the ventral tegmental area appear to have a critical role in fear processing, we aimed to investigate their contribution to the effects of ghrelin on fear processing. Our data show that systemic administration of the ghrelin receptor agonist MK0677, in a dose that induces food intake, has no significant effect on auditory fear processing and does not significantly affect dopamine release in the nucleus accumbens of male C57BL/6J mice. Local administration of the ghrelin receptor agonist MK0677 into the ventral tegmental area significantly increases food intake and it also significantly increased dopamine release in the nucleus accumbens, the medial prefrontal cortex and the amygdala. Nevertheless, it did not significantly affect auditory fear extinction. Our data indicate that pharmacological activation of midbrain dopamine neurons using a ghrelin receptor agonist does not affect auditory fear extinction. We also investigated the effect of non‐pharmacological manipulation of the ghrelin system on auditory fear processing. However, we found that neither overnight food deprivation nor genetic ablation of the ghrelin receptor had a significant effect on auditory fear extinction. We conclude that the effects of manipulation of the ghrelin system on fear processing are subject to boundary conditions that remain poorly understood. image

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Section: Discussionmentioning

confidence: 99%

Effects of ghrelin receptor activation on forebrain dopamine release, conditioned fear and fear extinction in C57BL/6J mice

Pierre

Schuerbeek

Allaoui

et al. 2020

Journal of Neurochemistry

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“…For example, Rescorla (2008) has argued that, during extinction, inhibition accrues to a unique configural cue, X, which represents the conjunction of a CS in its extinction context (see also Harris et al 2000;Holmes and Westbrook 2013;Holmes et al 2014). Hence, presentation of an extinguished CS inside its extinction context yields low levels of performance, while presentation of an extinguished CS in a different context, one matched with the extinction context for its associative history, removes the influence of inhibition accrued to X and renews performance (in either ABA or ABC designs).…”

Section: Discussionmentioning

confidence: 99%

Counterconditioned fear responses exhibit greater renewal than extinguished fear responses

2016

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This series of experiments used rats to compare counterconditioning and extinction of conditioned fear responses (freezing) with respect to the effects of a context shift. In each experiment, a stimulus was paired with shock in context A, extinguished or counterconditioned through pairings with sucrose in context B, and then tested for renewal outside of context B. Counterconditioned fear responses exhibited greater ABA renewal than extinguished fear responses. This result was observed using a between-subjects design (Experiment 1) and a within-subject design in which counterconditioned and extinguished stimuli were equated in all respects other than their signaling of sucrose (Experiment 2). Counterconditioned fear responses also exhibited greater ABC renewal than extinguished fear responses (Experiment 3). This result was observed using a within-subject design in which context C was identical to context B in terms of its associative history, and when counterconditioned and extinguished CSs were tested in compounds matched for their association with both shock and sucrose (Experiment 4). These results are consistent with models which hold that context regulates expression of associations formed in counterconditioning and extinction, and allow the level of regulation to be greater following counterconditioning than extinction, as noted in previous studies.One way to eliminate conditioned fear is extinction. A relatively innocuous stimulus, such as a tone, is first paired with an innate source of danger (typically, brief but aversive footshock in rodents). These pairings produce an association between the tone [conditioned stimulus (CS)] and the aversive foot shock [unconditioned stimulus (US)] that is expressed on subsequent presentations of the CS in a range of defensive responses indicative of fear in people. Extinction consists in repeated presentations of the CS in the absence of the aversive US. The fear responses, such as freezing, elicited by the CS decline across these presentations and eventually cease. Fear of the CS is said to be extinguished. It is now well-established that the learning produced by conditioning survives extinction in spite of the fact that the CS failed to elicit fear responses. For example, the fear response that has been extinguished can be restored by testing the CS outside the context where extinction occurred (renewal), interpolating US alone presentations between extinction and testing (reinstatement), or testing the CS sometime after extinction (spontaneous recovery). These fear restoration phenomena imply that extinction involves new learning that inhibits retrieval and/ or expression of the original learning in fear responses (Bouton 1991(Bouton , 1993(Bouton , 1994(Bouton , 2002(Bouton , 2004Delamater 2004;Delamater and Westbrook 2014).A second way to eliminate conditioned fear is counterconditioning. Here, the CS is again presented in the absence of the aversive shock US. However, in contrast to extinction where the CS is presented alone, in counterconditioning the CS is p...

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“…In each case, rats express what is learned about S1 and S2 in autonomic and defensive responses indicative of fear in people (Davis, 1992;Fanselow, 1998;McNally and Westbrook, 2006). Following Pavlov (1927), the fear elicited by S1 is termed first-order conditioned fear, and that elicited by S2 is termed second-order conditioned fear (Rizley and Rescorla, 1972;Yin et al, 1994;Parkes and Westbrook, 2010;Witnauer and Miller, 2011;Holmes et al, 2013Holmes et al, , 2014Leidl et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

2019

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Consolidation of conditioned fear to a stimulus (S1) paired with shock requires de novo protein synthesis in the basolateral amygdala complex (BLA), whereas consolidation of conditioned fear to a stimulus (S2) paired with the fear-eliciting S1 requires DNA methylation but not de novo protein synthesis in the BLA. The present experiments merged these protocols by exposing rats to pairings of a serial S2-S1 compound and shock to examine if/when protein synthesis in the BLA is required to consolidate fear to S2. Rats received a BLA infusion of the protein synthesis inhibitor, cycloheximide, immediately after the S2-S1-shock session and were subsequently tested with S2. The infusion disrupted consolidation of fear to S2 when there had been no prior training of S1 (Experiment 1), the prior training had consisted of unpaired presentations of S1 and shock (Experiment 4), or in pairings of S1 and sucrose (Experiment 5). Consolidation of fear to S2 was unaffected by the infusion of cycloheximide but was disrupted by the DNA methyltransferase inhibitor, 5-AZA, when S1 had been previously fear-conditioned (Experiments 2a, 2b, and 3). These findings imply that what has already been learned about S1 determines the BLA processes that consolidate fear to S2. The already-fear-conditioned S1 blocks the S2-shock association that otherwise forms (and whose consolidation requires de novo protein synthesis in the BLA) while simultaneously acting as a learned source of danger for its S2 associate (whose consolidation requires DNA methylation but not de novo protein synthesis in the BLA).

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Extinguished second-order conditioned fear responses are renewed but not reinstated.

Cited by 19 publications

References 33 publications

Effects of ghrelin receptor activation on forebrain dopamine release, conditioned fear and fear extinction in C57BL/6J mice

Effects of ghrelin receptor activation on forebrain dopamine release, conditioned fear and fear extinction in C57BL/6J mice

Counterconditioned fear responses exhibit greater renewal than extinguished fear responses

The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

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