Behavioral control blunts reactions to contemporaneous and future adverse events: Medial prefrontal cortex plasticity and a corticostriatal network
Open accessAbstract
It has been known for many years that the ability to exert behavioral control over an adverse event blunts the behavioral and neurochemical impact of the event. More recently, it has become clear that the experience of behavioral control over adverse events also produces enduring changes that reduce the effects of subsequent negative events, even if they are uncontrollable and quite different from the original event controlled. This review focuses on the mechanism by which control both limits the impact of the stressor being experienced and produces enduring, trans-situational "immunization". The evidence will suggest that control is detected by a corticostriatal circuit involving the ventral medial prefrontal cortex (mPFC) and the posterior dorsomedial striatum (DMS). Once control is detected, other mPFC neurons that project to stress-responsive brainstem (dorsal raphe nucleus, DRN) and limbic (amygdala) structures exert top-down inhibitory control over the activation of these structures that is produced by the adverse event. These structures, such as the DRN and amygdala, in turn regulate the proximate mediators of the behavioral and physiological responses produced by adverse events, and so control blunts these responses. Importantly, the joint occurrence of control and adverse events seems to produce enduring plastic changes in the top-down inhibitory mPFC system such that this system is now activated by later adverse events even if they are uncontrollable, thereby reducing the impact of these events. Other issues are discussed that include a) whether other processes such as safety signals and exercise, that lead to resistance/resilience, also use the mPFC circuitry or do so in other ways; b) whether control has similar effects and neural mediation in humans, and c) the relationship of this work to clinical phenomena.
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Exercising behavioral control over aversive stimuli can persistently diminish learned threat responses in rodents.
“Studies in rodents suggest that exercising behavioral control over aversive stimuli can persistently diminish learned threat responses (Cain and LeDoux, 2007; Maier, 2015; LeDoux et al., 2017).”
From Active avoidance: Neural mechanisms and attenuation of pavlovian conditioned responding (2017) · cites this paper as Maier, 2015
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- Authors
- Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Maier, Steven F.
- ORCID
- Maier, Steven F.
- Venue
- Neurobiology of Stress
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 1
- Pages
- 12-22
- ISSN
- 2352-2895 (ISSN-L)
- PMC
- PMC4260419
- OpenAlex
- W2009382390
- Cited by
- 143
- References
- 94
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 12 · 2021: 14 · 2020: 10 · 2019: 16 · 2018: 20 · 2017: 19 · 2016: 16 · 2015: 6
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Stress (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Mental Health (R37MH050479, R01MH050479)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- behavioral control, adverse events, stress resilience, medial prefrontal cortex, dorsomedial striatum, corticostriatal circuits, dorsal raphe nucleus, amygdala, top-down inhibition, neuroplasticity, safety signals, physical activity, stress tolerance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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