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Neurons in medial prefrontal cortex signal memory for fear extinction

Author

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  • Mohammed R. Milad

    (Ponce School of Medicine)

  • Gregory J. Quirk

    (Ponce School of Medicine)

Abstract

Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov1 it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction2,3, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.

Suggested Citation

  • Mohammed R. Milad & Gregory J. Quirk, 2002. "Neurons in medial prefrontal cortex signal memory for fear extinction," Nature, Nature, vol. 420(6911), pages 70-74, November.
  • Handle: RePEc:nat:nature:v:420:y:2002:i:6911:d:10.1038_nature01138
    DOI: 10.1038/nature01138
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    Cited by:

    1. Bo Zhou & David E. Moorman & Sam Behseta & Hernando Ombao & Babak Shahbaba, 2016. "A Dynamic Bayesian Model for Characterizing Cross-Neuronal Interactions During Decision-Making," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 111(514), pages 459-471, April.
    2. Zai-Fu Yao & Shulan Hsieh, 2019. "Neurocognitive Mechanism of Human Resilience: A Conceptual Framework and Empirical Review," IJERPH, MDPI, vol. 16(24), pages 1-21, December.
    3. Robert N. Fetcho & Baila S. Hall & David J. Estrin & Alexander P. Walsh & Peter J. Schuette & Jesse Kaminsky & Ashna Singh & Jacob Roshgodal & Charlotte C. Bavley & Viraj Nadkarni & Susan Antigua & Th, 2023. "Regulation of social interaction in mice by a frontostriatal circuit modulated by established hierarchical relationships," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Cheng-Hao Yang & Xiang-Ming Liu & Ji-Jian Si & Hai-Shui Shi & Yan-Xue Xue & Jian-Feng Liu & Yi-Xiao Luo & Chen Chen & Peng Li & Jian-Li Yang & Ping Wu & Lin Lu, 2012. "Role of IKK/NF-κB Signaling in Extinction of Conditioned Place Aversion Memory in Rats," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-8, June.
    5. Emily Tang & Chelsea Jones & Lorraine Smith-MacDonald & Matthew R. G. Brown & Eric H. G. J. M. Vermetten & Suzette Brémault-Phillips, 2021. "Decreased Emotional Dysregulation Following Multi-Modal Motion-Assisted Memory Desensitization and Reconsolidation Therapy (3MDR): Identifying Possible Driving Factors in Remediation of Treatment-Resi," IJERPH, MDPI, vol. 18(22), pages 1-12, November.
    6. Mouna Maroun & Alexandra Kavushansky & Andrew Holmes & Cara Wellman & Helen Motanis, 2012. "Enhanced Extinction of Aversive Memories by High-Frequency Stimulation of the Rat Infralimbic Cortex," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-8, May.
    7. Anthony Burgos-Robles & Hector Bravo-Rivera & Gregory J Quirk, 2013. "Prelimbic and Infralimbic Neurons Signal Distinct Aspects of Appetitive Instrumental Behavior," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-7, February.

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