Extinction depends, at least partly, on new learning that is specific to the context in which it is learned. Several behavioral phenomena (renewal, reinstatement, spontaneous recovery, and rapid reacquisition) suggest the importance of context in extinction. The present article reviews research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval. Contexts appear to select or retrieve the current relationship of the conditional stimulus (CS) with the unconditional stimulus (US), and they are provided by physical background cues, interoceptive drug cues, emotions, recent trials, and the passage of time. The current article pays particular attention to the effects of recent trials and trial spacing. Control of fear extinction by physical context involves interactions between the dorsal hippocampus and the lateral nucleus of the amygdala. This interaction may be mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.
The amygdala has long been considered to be both necessary and sufficient for classical fear conditioning, but recent evidence suggests that the medial prefrontal cortex (mPFC) may also be involved. The prelimbic (PL) subregion of mPFC projects to the amygdala, and neurons in PL show fear-related increases in activity. It is unknown, however, whether PL activity is necessary for expression of learned fears, expression of innate fears, or the learning of fear associations. To address this, we used the sodium channel blocker tetrodotoxin to inactivate PL during fear learning or expression. Inactivation of PL reduced freezing to both a tone and a context that had been previously paired with footshock (learned fear) but had no effect on freezing to a cat (innate fear). Inactivation of PL before conditioning, however, did not prevent the formation of auditory or contextual fear memories. Thus, activity in PL is critical for the expression, but not the acquisition, of learned fears. We suggest that PL integrates information from auditory and contextual inputs and regulates expression of fear memories via projections to the basal nucleus of the amygdala.
Recent studies implicate the hippocampus in contextual memory retrieval. The present experiments explore this possibility by examining the impact of reversible inactivation of the dorsal hippocampus (DH) on the context-specific expression of extinction. In experiment 1, rats were conditioned to fear a tone conditional stimulus (CS) and subsequently extinguished either in the same context as conditioning or in a novel context. A third group of rats underwent fear conditioning but did not receive extinction. After extinction, conditional fear to the tone CS was assessed in the conditioning context by measuring freezing. Rats extinguished in the conditioning context exhibited low levels of freezing, whereas those extinguished in a different context and those that received no extinction showed high levels of freezing. This indicates that the expression of extinction is context-specific. In experiment 2, the context-specific expression of extinction was disrupted by infusion of muscimol, a GABA(A) receptor agonist, into the DH. Rats that received muscimol infusions into the DH showed little freezing to the tone CS, regardless of whether the CS had been extinguished in the testing context or another context. In experiment 3, intrahippocampal muscimol infusions did not disrupt the expression of conditional freezing to the tone CS in rats that did not receive extinction. Thus, muscimol infusion into the DH produced a selective impairment in the context-specific expression of extinction. These results extend findings from other behavioral paradigms and provide additional support for a role for the hippocampus in contextual memory retrieval.
In recent studies, inactivation of the dorsal hippocampus before the retrieval of extinguished fear memories disrupted the contextdependent expression of these memories. In the present experiments, we examined the role of the dorsal hippocampus in the acquisition of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock [unconditional stimulus (US)], rats received an extinction session in which the CS was presented without the US. In experiment 1, infusion of muscimol, a GABA A receptor agonist, into the dorsal hippocampus before the extinction training session decreased the rate of extinction. Moreover, when later tested for fear to the extinguished CS, all rats that had received hippocampal inactivation before extinction training demonstrated renewed fear regardless of the context in which testing took place. This suggests a role for the dorsal hippocampus in both acquiring the extinction memory and encoding the CS-context relationship that yields the context dependence of extinction. In experiment 2, inactivation of the dorsal hippocampus before testing also disrupted the context dependence of fear to the extinguished CS. In experiment 3, quantitative autoradiography revealed the boundaries of muscimol diffusion after infusion into the dorsal hippocampus. Together, these results reveal that the dorsal hippocampus is involved in the acquisition, contextual encoding, and context-dependent retrieval of fear extinction. Learning and remembering when and where aversive events occur is essential for adaptive emotional regulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with đź’™ for researchers
Part of the Research Solutions Family.