Altered fear learning across development in both mouse and human
Open accessAbstract
The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective.
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Cross-species evidence suggests that extinction is diminished during adolescence relative to childhood and adulthood.
“Moreover, cross-species evidence suggests that extinction is diminished during adolescence relative to childhood and adulthood (10).”
From When Uncertainty Is a Certainty: Optimizing Exposure-Based Therapies (2021) · cites this paper as [10]
Fear extinction during adolescence is reduced in both humans and mice.
“fear extinction during adolescence is reduced in both humans and mice [26]”
From Towards a youth mental health paradigm: a perspective and roadmap (2023) · cites this paper as [26]
Adolescents show attenuated fear extinction learning relative to children and adults, although all groups show similar acquisition of cued fear.
“Although all groups showed similar acquisition of cued fear, the adolescents showed attenuated fear extinction learning relative to children and adults (Pattwell et al., 2012).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Pattwell et al., 2012
Immunohistochemical evidence points to reduced synaptic plasticity in areas of the mPFC after extinction recall in adolescent rodents.
“Immunohistochemical evidence points to reduced synaptic plasticity in areas of the mPFC after extinction recall in adolescent rodents7,10.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [7]
Adolescents continue to show signs of defensive responding to previously learned threat cues, suggesting an age-specific relative dysregulation of the process that updates threat associations as safe.
“For example, adolescents continue to show signs of defensive responding to previously learned threat cues (freezing in rodents and elevated skin conductance in humans), suggesting an age-specific relative dysregulation of the process that updates threat associations as safe7,10–13.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [7]
In vulnerable populations such as children and adolescents, sound stimuli are recommended over mild electric shocks in threat conditioning paradigms.
“In vulnerable populations, such as children and adolescents, sound stimuli are recommended over mild electric shocks in threat conditioning paradigms7,8,13,43.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [7]
Recent research with rodents and humans has shown distinctive developmental profiles of blunted threat extinction recall in adolescents relative to children and adults.
“Recent research with rodents and humans has shown distinctive developmental profiles of blunted threat extinction recall in adolescents6–11, relative to children and adults.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [7]
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- Authors
- Pattwell, S. S., Duhoux, S., Hartley, C. A., Johnson, D. C., Jing, D., Elliott, M. D., Ruberry, E. J., Powers, A., Mehta, N., Yang, R. R., Soliman, F., Glatt, C. E., Casey, B. J., Ninan, I., & Lee, F. S.
- Affiliations
- Cornell University (US)
- Department of Psychiatry,
- New York University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-17
- Volume
- 109
- Issue
- 40
- Pages
- 16318-16323
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3479553
- OpenAlex
- W1996307224
- Cited by
- 404
- References
- 57
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 25 · 2023: 20 · 2022: 24 · 2021: 29 · 2020: 38 · 2019: 42 · 2018: 28 · 2017: 36 · 2016: 42 · 2015: 28 · 2014: 25 · 2013: 23 · 2012: 1
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- New York Community Trust
- International Mental Health Research Organization
- Monique Weill-Caulier Trust
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (123643)
- National Institutes of Health (MH079513)
- National Institute of Mental Health (P50MH079513, MH079513)
- National Institute of General Medical Sciences (T32GM007739)
- National Institute of Neurological Disorders and Stroke (NS052819, R01NS052819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD055177, T32HD055177)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fear extinction learning, fear learning, development (biology), adolescence, synaptic plasticity, prefrontal cortex, anxiety disorders, stress-related disorders, exposure therapy, treatment response, individual differences, mouse model
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Animals, Anxiety Disorders, Child, Conditioning, Psychological, Extinction, Psychological, Fear, Female, Galvanic Skin Response, Humans, Immunohistochemistry, Male, Microscopy, Interference, Neuronal Plasticity, Proto-Oncogene Proteins c-fos, Prefrontal Cortex, Mice
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