Cited by 143Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorMemory and Neural Mechanisms

Behavioral control blunts reactions to contemporaneous and future adverse events: Medial prefrontal cortex plasticity and a corticostriatal network

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Maier, Steven F.·2015·Neurobiology of Stress

Abstract

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).”

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Research works printed but not linked: 2

  1. Amat J. Prior experience with behavioral control over stress blocks the behavioral effects of later uncontrollable stress: role of the ventral medial prefrontal cortex J. Neurosci. 2006 26 PMC6675012 17182776
  2. Strong P.V. 5–HT2C receptors in the dorsal striatum mediate the expression of instrumental learning deficits after uncontrollable stress J. Neurosci. 97 2011 132 144 PMC3235414 21958863

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Authors
Maier, S. F.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Maier, Steven F.
Venue
Neurobiology of Stress
Publisher
Elsevier BV
Published
2015-01
Volume
1
Pages
12-22
ISSN
2352-2895 (ISSN-L)
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
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

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