Erasing Fear Memories with Extinction Training: Figure 1.

Quirk, Gregory J.; Paré, Denis; Richardson, Rick; Herry, Cyril; Monfils, Marie‐H.; Schiller, Daniela; Vicentic, Aleksandra

doi:10.1523/jneurosci.4268-10.2010

Cited by 206 publications

(178 citation statements)

References 67 publications

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“…Traditionally, extinction has been thought of not as an erasure or reversal of the initial fear memory but rather as leading to the formation of a new inhibitory memory, based on the behavioral properties of extinction such as spontaneous recovery (28). Interestingly, we do not observe a spontaneous recovery (the return of the conditioned fear response) of freezing behavior 3 wk following olfactory extinction (Fig.…”

Section: Discussionmentioning

confidence: 59%

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Morrison

Dias

Ressler

2015

Proc. Natl. Acad. Sci. U.S.A.

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Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learninginduced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.fear extinction | olfaction | neural plasticity I ncreasing evidence suggests that the cellular, neuroanatomical, and receptive field organizations of vertebrate sensory systems are continually reshaped throughout adulthood by cues from the external environment. Activity-dependent changes are known to occur both during critical periods of development and also in the adult brain, allowing the animal to optimally perform behaviors based on the demands of the surrounding environment. Postmitotic organizational changes, along with activity-dependent plasticity, have been largely implicated in shaping sensory circuits from development through adulthood (1-4). In particular, the olfactory sensory system of adult mice exhibits functional and neuroanatomical learning-dependent changes following olfactory fear conditioning in adulthood (5-7). The M71-LacZ transgenic mouse line expresses LacZ under the M71 odorant receptor (OR) promoter (encoded by the olfactory receptor 151 gene, Olfr151) (8) in the M71 OR-expressing, acetophenone-responsive population of olfactory sensory neurons (OSNs). Using this line, we previously demonstrated an increased number of M71-expressing OSNs in the main olfactory epithelium (MOE) of adult mice following olfactory fear conditioning to acetophenone (5, 7), an odorant that activates the M71/M72 ORs (9, 10). This increase in receptor-specific OSNs within the MOE was directly correlated with an increase in the area of M71+ axons innervating the M71 glomeruli within the olfactory bulbs (OBs). Behaviorally, these olfactory fear-conditioned mice also exhibited enhanced fear-potentiated startle (FPS) and freezing specific to the conditioned odor stimulus. Notably such changes were never seen with equivalent odorant exposure alone but only when the odorant was paired with an aversive or appetitive cue (5, 7), sugges...

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Section: Discussionmentioning

confidence: 59%

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Morrison

Dias

Ressler

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…1C). Thus, the pupil CR did not undergo reversal, in terms of tone affiliation, after contingency reversal, but rather "extinguished" then (23)(24)(25)(26). This remains the case even when considering only later parts of phase 3.…”

Section: Resultsmentioning

confidence: 86%

Plasticity of human auditory-evoked fields induced by shock conditioning and contingency reversal

Kluge

Bauer

Leff

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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We used magnetoencephalography (MEG) to assess plasticity of human auditory cortex induced by classical conditioning and contingency reversal. Participants listened to random sequences of high or low tones. A first baseline phase presented these without further associations. In phase 2, one of the frequencies (CS + ) was paired with shock on half its occurrences, whereas the other frequency (CS − ) was not. In phase 3, the contingency assigning CS + and CS − was reversed. Conditioned pupil dilation was observed in phase 2 but extinguished in phase 3. MEG revealed that, during phase-2 initial conditioning, the P1m, N1m, and P2m auditory components, measured from sensors over auditory temporal cortex, came to distinguish between CS + and CS − . After contingency reversal in phase 3, the later P2m component rapidly reversed its selectivity (unlike the pupil response) but the earlier P1m did not, whereas N1m showed some new learning but not reversal. These results confirm plasticity of human auditory responses due to classical conditioning, but go further in revealing distinct constraints on different levels of the auditory hierarchy. The later P2m component can reverse affiliation immediately in accord with an updated expectancy after contingency reversal, whereas the earlier auditory components cannot. These findings indicate distinct cognitive and emotional influences on auditory processing.

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“…The association between human reality filtering and the capacity to abandon previously valid anticipations suggests that extinction trials in reward tasks would be an appropriate animal model of human reality filtering. In contrast to extinction of fear memories (in which the animals gain access to a previously avoided stimulus) (LeDoux, 1996;Quirk et al, 2010) extinction of reward associations (in which the animals give up a previously rewarding association) has rarely been studied because such trials rapidly discourage the animals from participating. Experimentation would Frontiers in Behavioral Neuroscience www.frontiersin.org thus take longer.…”

Section: Perspectivesmentioning

confidence: 99%

Orbitofrontal reality filtering

Schnider¹

2017

Oxford Scholarship Online

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Decades of research have deepened our understanding of how the brain forms memories and uses them to build our mental past and future. But how does it determine whether an evoked memory refers to the present and can be acted upon? The study of patients who confuse reality, as evident from confabulation and disorientation, has opened ways to explore this vital capacity. Results indicate that the brain recurs to a phylogenetically old faculty of the orbitofrontal cortex -extinction -and structures of the reward system to keep thought and behavior in phase with reality.

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Erasing Fear Memories with Extinction Training: Figure 1.

Cited by 206 publications

References 67 publications

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Plasticity of human auditory-evoked fields induced by shock conditioning and contingency reversal

Orbitofrontal reality filtering

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