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Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction
Open accessAbstract
Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction.
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“One consequence of stress-related PFC impairment is enhanced threat learning and impaired extinction retention in rodent models [66, 70].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [70]
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“In rodents, chronic stress also impacts neural activity in both PL and IL cortex [70] and leads to structural changes in IL cortex [71].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [70]
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Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects
Mahar, I., Bambico, F. R., Mechawar, N., & Nobrega, J. N. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.009 · Cited by 694
Maren, S., & Holmes, A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.180 · Cited by 412
Prefrontal cortex, amygdala, and threat processing: implications for PTSD
Alexandra Kredlow, M., Fenster, R. J., Laurent, E. S., Ressler, K. J., & Phelps, E. A. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01155-7 · Cited by 346
“In rodents, chronic stress also impacts neural activity in both PL and IL cortex [70] and leads to structural changes in IL cortex [71].”
BackgroundEpigenetics of stress adaptations in the brain
Stankiewicz, A. M., Swiergiel, A. H., & Lisowski, P. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.07.003 · Cited by 220
Single prolonged stress disrupts retention of extinguished fear in rats.Preprint
Knox, D., George, S. A., Fitzpatrick, C. J., Rabinak, C. A., Maren, S., & Liberzon, I. (2012) · Learning & memory (Cold Spring Harbor, N.Y.) · doi:10.1101/lm.024356.111 · Cited by 202
Metadata
- Authors
- Wilber, A. A., Walker, A. G., Southwood, C. J., Farrell, M. R., Lin, G. L., Rebec, G. V., & Wellman, C. L.
- Affiliations
- Indiana University Bloomington (US)
- Corresponding author
- Wellman, C.L.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 174
- Pages
- 115-131
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3020264
- OpenAlex
- W2039543325
- Semantic Scholar
- ec3c2ff6cfebae04751b5903c47df5b3116789fa
- Cited by
- 115
- References
- 59
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 12 · 2018: 10 · 2017: 5 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 14 · 2012: 10
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (MHR03087794)
- National Institute of Mental Health (F31MH085415, R03MH087794)
- National Institute of Neurological Disorders and Stroke (F31NS066603, F31NS064791)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- chronic restraint stress, medial prefrontal cortex, infralimbic cortex, prelimbic cortex, extinction retrieval, fear extinction, fear conditioning, neuronal firing, conditioned stimulus, neuronal activity
- MeSH terms
- Action Potentials, Animals, Conditioning, Operant, Extinction, Psychological, Fear, Male, Neurons, Restraint, Physical, Stress, Psychological, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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