Neuronal signalling of fear memory

Maren, Stephen; Quirk, Gregory J.

doi:10.1038/nrn1535

Cited by 1,313 publications

(1,073 citation statements)

References 105 publications

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“…Abnormally high psychophysiological conditioned responses to reminders of traumatic events can persist as long as 50 years following its cessation (Orr et al, 1993). These data suggest that a deficit in either extinction learning or retention of that learning may underlie failure to recover from the effects of the traumatic stressor (Rauch et al, 2006;Milad et al, 2006b;Davis et al, 2006;SotresBayon et al, 2004;Maren and Quirk, 2004). Consistent with this view, slower extinction of corrugator electromyogram responses were found to represent a pre-trauma risk factor for PTSD-related symptoms following a traumatic event (Guthrie and Bryant, 2006).…”

Section: Introductionmentioning

confidence: 88%

Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Milad

Orr

Lasko

et al. 2008

Journal of Psychiatric Research

464

393

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Recall of fear extinction, which is thought to aid in recovery from a psychologically traumatic event, is hypothesized to be deficient in post-traumatic stress disorder (PTSD), but this has not yet been demonstrated in the laboratory, nor has its origin been investigated. To address these two issues, 14 pairs of monozygotic twins discordant for combat exposure, in 7 of which the combat-exposed twin had PTSD, underwent a two-day fear conditioning and extinction procedure. On Day 1, subjects viewed colored light conditioned stimuli, some of which were paired with mild electric shock, followed by extinction of the conditioned responses. On Day 2, recall of Day 1 extinction learning (i.e., extinction retention) was assessed. Skin conductance response (SCR) was the dependent measure. There were no group differences during acquisition or extinction learning. However, a significant PTSD Diagnosis (in the exposed twin) x combat Exposure interaction emerged during extinction recall, with the PTSD combat veterans having larger SCRs than their own co-twins, and than the non-PTSD combat veterans and their co-twins. These results indicate that retention of extinction of conditioned fear is deficient in PTSD. Furthermore, they support the conclusion that this deficit is acquired as a result of combat trauma leading to PTSD, rather than being a predisposing factor to developing PTSD upon the stress of combat.

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Section: Introductionmentioning

confidence: 88%

Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Milad

Orr

Lasko

et al. 2008

Journal of Psychiatric Research

464

393

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“…The infralimbic medial prefrontal cortex (IL) and basolateral amygdala (BLA) are implicated in acquisition of conditioned fear responses [102]. Moreover, plasticity in these regions is believed to mediate reversal of conditioned fear responses with extinction [103,104]. Peña et al [101] hypothesized that VNS may alter the strength of connections between these areas to enhance the extinction of fear.…”

Section: Preclinical Studies For Post-traumatic Stress Disordermentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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“…Taken together, these previous results suggested that NMDARs in the amygdala are involved in the retention/ consolidation of the long-term extinction memory, but not its initial acquisition (Maren and Quirk, 2004). However, the results are inconclusive, because side effects of the two drugs used to block NMDARs may have interfered with assessment of extinction acquisition during the training session.…”

Section: Introductionmentioning

confidence: 95%

“…Current models for fear extinction propose interactions between the amygdala, medial prefrontal cortex, and hippocampus (Maren and Quirk, 2004;Sotres-Bayon et al, 2004. Understanding the phase of learning and memory (acquisition, consolidation, retention, retrieval) during which each structure participates in extinction will provide a deeper understanding of the mechanisms involved and may lead to better ways to treat fear and anxiety disorders.…”

Section: Lateral Amygdala In the Acquisition Of Fear Extinctionmentioning

confidence: 99%

“…Although fear extinction also involves the amygdala (Davis et al, 2003), its role is less clear than in fear conditioning (Maren and Quirk, 2004;Sotres-Bayon et al, 2004). Much of the evidence implicating the amygdala in fear extinction has involved studies showing that blockade of N-methyl-D-aspartate receptors (NMDARs) in the lateral and basal amygdala, using APV (D,L-2-amino-5-phosphonovaleric acid), prevents the decrease in responding that normally occurs during extinction learning, as assessed in a later test (Falls et al, 1992;Lin et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Sotres-Bayón

Bush

LeDoux

2007

Neuropsychopharmacol

257

207

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N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction.

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Neuronal signalling of fear memory

Cited by 1,313 publications

References 105 publications

Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

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