Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Daniela Schiller, Jonathan W. Kanen, Joseph E. LeDoux, Marie-H. Monfils and Elizabeth A. Phelps
PNAS November 25, 2013. 201320322; published ahead of print November 25, 2013. https://doi.org/10.1073/pnas.1320322110
Daniela Schiller
aDepartment of Psychiatry, Department of Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mt. Sinai, New York, NY 10029;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: daniela.schiller@mssm.eduliz.phelps@nyu.eduledoux@cns.nyu.edu
Jonathan W. Kanen
bDepartment of Psychology and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph E. LeDoux
cCenter for Neural Science, New York University, New York, NY 10003;dNathan Kline Institute, Orangeburg, NY 10962; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: daniela.schiller@mssm.eduliz.phelps@nyu.eduledoux@cns.nyu.edu
Marie-H. Monfils
eDepartment of Psychology, University of Texas at Austin, Austin, TX 78712
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth A. Phelps
bDepartment of Psychology andcCenter for Neural Science, New York University, New York, NY 10003;dNathan Kline Institute, Orangeburg, NY 10962; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: daniela.schiller@mssm.eduliz.phelps@nyu.eduledoux@cns.nyu.edu
  1. Contributed by Joseph E. LeDoux, October 30, 2013 (sent for review August 13, 2013)

  • Article
  • Authors & Info
  • PDF
Loading

Significance

An advantage of targeting reconsolidation to control reactions to learned threats is that the memory appears to be persistently altered, not inhibited. When these memories are diminished through extinction, the amygdala’s representation remains largely intact and the prefrontal cortex inhibits its expression, thus allowing the learned responses to recover. Targeting reconsolidation, therefore, should eliminate the necessity of prefrontal inhibition. We tested this hypothesis by contrasting standard extinction with extinction occurring during reconsolidation. We observed that behavioral interference of reconsolidation appears to bypass the prefrontal circuitry of extinction, inducing a more persistent loss of learned responses. Application of this strategy, which targets underlying learned threat processes, to fear and anxiety disorders may provide a more effective approach to treatment.

Abstract

Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders.

  • fear
  • Pavlovian conditioning
  • defense
  • learning

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: daniela.schiller{at}mssm.edu, liz.phelps{at}nyu.edu, or ledoux{at}cns.nyu.edu.
  • Author contributions: D.S., J.E.L., M.H.M., and E.A.P. designed research; D.S. and J.W.K. performed research; D.S., J.W.K., and E.A.P. analyzed data; and D.S., J.W.K., J.E.L., and E.A.P. wrote the paper.

  • The authors declare no conflict of interest.

Freely available online through the PNAS open access option.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
Extinction during reconsolidation
Daniela Schiller, Jonathan W. Kanen, Joseph E. LeDoux, Marie-H. Monfils, Elizabeth A. Phelps
Proceedings of the National Academy of Sciences Nov 2013, 201320322; DOI: 10.1073/pnas.1320322110

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Extinction during reconsolidation
Daniela Schiller, Jonathan W. Kanen, Joseph E. LeDoux, Marie-H. Monfils, Elizabeth A. Phelps
Proceedings of the National Academy of Sciences Nov 2013, 201320322; DOI: 10.1073/pnas.1320322110
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

More Articles of This Classification

Social Sciences

  • Neural precursors of future liking and affective reciprocity
  • The Matthew effect in science funding
  • Social contagion of ethnic hostility
Show more

Psychological and Cognitive Sciences

  • Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress
  • The computational form of craving is a selective multiplication of economic value
  • Individuals, institutions, and innovation in the debates of the French Revolution
Show more

Biological Sciences

  • β-Amyloid accumulation in the human brain after one night of sleep deprivation
  • Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction
  • Nucleus-specific expression in the multinuclear mushroom-forming fungus Agaricus bisporus reveals different nuclear regulatory programs
Show more

Neuroscience

  • Long-wavelength (reddish) hues induce unusually large gamma oscillations in the primate primary visual cortex
  • Neural precursors of future liking and affective reciprocity
  • Spider toxin inhibits gating pore currents underlying periodic paralysis
Show more

Related Content

  • No related articles found.
  • Scopus
  • PubMed
  • Google Scholar

Cited by...

  • REM Sleep Is Causal to Successful Consolidation of Dangerous and Safety Stimuli and Reduces Return of Fear after Extinction
  • Dissociating Value Representation and Inhibition of Inappropriate Affective Response during Reversal Learning in the Ventromedial Prefrontal Cortex
  • Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval
  • Pathway-Selective Adjustment of Prefrontal-Amygdala Transmission during Fear Encoding
  • Young and old Pavlovian fear memories can be modified with extinction training during reconsolidation in humans
  • Hippocampal molecular mechanisms involved in the enhancement of fear extinction caused by exposure to novelty
  • Scopus (89)
  • Google Scholar

Similar Articles

You May Also be Interested in

Karina Guziewicz and Artur Cideciyan explain a potential gene therapy approach for macular degeneration.
Gene therapy for retinal disease
Karina Guziewicz and Artur Cideciyan explain a potential gene therapy approach for macular degeneration.
Listen
Past PodcastsSubscribe
PNAS Profile of Alexander Rudensky, winner of the Vilcek Prize in Biomedical Science
PNAS Profile
PNAS Profile of Alexander Rudensky, winner of the Vilcek Prize in Biomedical Science
Ambrosia beetles, which bore into host trees and cultivate fungi, select trees with elevated ethanol content because ethanol promotes growth of preferred fungal species.
Fungus-farming beetles use alcohol to screen symbionts
Ambrosia beetles, which bore into host trees and cultivate fungi, select trees with elevated ethanol content because ethanol promotes growth of preferred fungal species.
Image courtesy of Gernot Kunz (Karl-Franzens-Universität Graz, Graz, Austria).
A study examines the walking and climbing capabilities of human ancestors.
Evolution of human locomotion
A study examines the walking and climbing capabilities of human ancestors.
Researchers have engineered the complete biosynthetic pathway for a potential cancer drug into a single yeast strain, paving the way toward the commercial brewing of medically important compounds.
Brewer’s yeast engineered to produce potential cancer drug
Researchers have engineered the complete biosynthetic pathway for a potential cancer drug into a single yeast strain, paving the way toward the commercial brewing of medically important compounds.
Image courtesy of Pixabay/Republica.
Proceedings of the National Academy of Sciences: 115 (17)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Authors & Info
  • PDF
Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information for

  • Authors
  • Reviewers
  • Press

Feedback    Privacy/Legal

Copyright © 2018 National Academy of Sciences.