Parallel circuits mediating distinct emotional coping reactions to different types of stress
Abstract
All animals, including humans, react with distinct emotional coping strategies to different types of stress. Active coping strategies (e.g. confrontation, fight, escape) are evoked if the stressor is controllable or escapable. Passive coping strategies (e.g. quiescence, immobility, decreased responsiveness to the environment) are usually elicited if the stressor is inescapable and help to facilitate recovery and healing. Neural substrates mediating active versus passive emotional coping have been identified within distinct, longitudinal neuronal columns of the midbrain periaqueductal gray (PAG) region. Active coping is evoked by activation of either the dorsolateral or lateral columns of the PAG; whereas passive coping is triggered by activation of the ventrolateral PAG. Recent anatomical studies indicate that each PAG column receives a distinctive set of ascending (spinal and medullary) and descending (prefrontal cortical and hypothalamic) afferents. Consistent with the anatomy, functional studies using immediate early gene expression (c-fos) as a marker of neuronal activation have revealed that the preferential activation of a specific PAG column reflects (i) the type of emotional coping reaction triggered, and (ii) whether a physical or psychological stressor was used.
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Flight or fight is mediated through the lateral periaqueductal gray (LPAG), which activates the basic, stereotypical motor patterns of flight or fight-for example, attack, running, treading, burying.
“Flight or fight is mediated through the lateral periaqueductal gray (LPAG), which activates the basic, stereotypical motor patterns of flight or fight—for example, attack, running, treading, burying (see Figures 1 and 2).24,28,47,48”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
The LPAG activates premotor centers in the pons and medulla, which then activate motor networks in the spinal cord or brain stem.
“The LPAG, in turn, activates premotor centers in the pons and medulla, which then activate motor networks in the spinal cord or brain stem.28,47”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
Activation of autonomic centers in the dorsal hypothalamus causes a generalized sympathetic response that includes activation of the heart and increased vascular resistance in the viscera, which increases perfusion pressure of tissues, especially muscles, heart, and brain.
“Activation of autonomic centers in the dorsal hypothalamus causes a generalized sympathetic response that includes activation of the heart (increased heart rate and cardiac output) and increased vascular resistance in the viscera, which increases the perfusion pressure of tissues, especially the muscles, heart, and brain.24,28”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
Flight or fight involves non-opioid analgesia, which can be evoked by activation of the LPAG, and projections to the spinal cord block ascending pain signals.
“Flight or fight involves non-opioid analgesia,28,29 which can be evoked by activation of the LPAG.28 Projections to the spinal cord block ascending pain signals.30”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
Non-opioid analgesia accompanies the active defense responses (flight or fight), and opioid analgesia accompanies the passive defense responses (freezing, tonic immobility, collapsed immobility, and quiescent immobility).
“Non-opioid analgesia accompanies the “active” defense responses (flight or fight), and opioid analgesia accompanies the “passive” defense responses (freezing, tonic immobility, collapsed immobility, and quiescent immobility).28–30”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
A number of parallel pathways that include projections from the amygdala and VLPAG to the DMN are likely to mediate this inhibitory vagal response.
“A number of parallel pathways that include projections from the amygdala and VLPAG to the DMN28 are likely to mediate this inhibitory vagal response.”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
The integrated freeze response includes an opioid-mediated analgesia, which is itself mediated by the PAG and the rostral ventromedial medulla pain circuit.
“The integrated freeze response includes an opioid-mediated analgesia,28,29 which is itself mediated by the PAG and the rostral ventromedial medulla pain circuit.71”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
The waxy immobility that characterizes tonic immobility is mediated by activation of the VLPAG.
“The “waxy” immobility that characterizes tonic immobility is also mediated by activation of the VLPAG.28,47,97”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
The VLPAG receives signals from deep somatic (muscle, joint) or visceral tissues via the dorsal horn of the spinal cord, from the parabrachial nucleus, and from the vagal sensory nucleus (the solitary track nucleus).
“The VLPAG receives signals from deep somatic (muscle, joint) or visceral tissues via the dorsal horn of the spinal cord, from the parabrachial nucleus,25,94,95 and from the vagal sensory nucleus (the solitary track nucleus).28,96”
From Fear and the Defense Cascade (2015) · cites this paper as [28]
The fight or flight response involves non-opioid (endocannabinoid-mediated) analgesia evoked by the lateral PAG.
“Notably, the fight or flight response involves non-opioid (endocannabinoid-mediated) analgesia evoked by the lateral PAG (Keay and Bandler, 2001;Kozlowska et al., 2015).”
From A review of the relation between dissociation, memory, executive functioning and social cognition in military members and civilians with neuropsychiatric conditions (2016) · cites this paper as Keay and Bandler, 2001
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- Authors
- Keay, K. A., & Bandler, R.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Bandler, Richard
- ORCID
- Keay, Kevin A.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 25
- Issue
- 7-8
- Pages
- 669-678
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2006563521
- Cited by
- 512
- References
- 3
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 24 · 2023: 23 · 2022: 22 · 2021: 22 · 2020: 19 · 2019: 22 · 2018: 23 · 2017: 23 · 2016: 21 · 2015: 24 · 2014: 19 · 2013: 21 · 2012: 21
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- 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
- emotional coping, stress, periaqueductal gray, active coping, passive coping, immobility, Fos expression, neuronal activation, midbrain, psychological stress, physical stress
- MeSH terms
- Adaptation, Psychological, Animals, Emotions, Humans, Nerve Net, Stress, Psychological
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