Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear
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The purpose of the present study was to determine whether lesions of areas projected to by the central amygdaloid nucleus (ACE) would disrupt the classical conditioning of autonomic and/or behavioral emotional responses. The areas studied included 3 projection targets of the ACE: the lateral hypothalamic area (LH), midbrain central gray (CG) region, and bed nucleus of the stria terminalis (BNST). Lesions were made either electrolytically or by microinjection of ibotenic acid, which destroys local neurons without interrupting fibers of passage. Two weeks later, the animals were classically conditioned by pairing an acoustic stimulus with footshock. The next day, conditioned changes in autonomic activity (increases in arterial pressure) and emotional behavior (“freezing,” or the arrest of somatomotor activity) evoked by the acoustic conditioned stimulus (CS) were measured during extinction trials. Electrolytic and ibotenic acid lesions of the LH interfered with the conditioned arterial pressure response, but did not affect conditioned freezing. Electrolytic lesions of the rostral CG disrupted conditioned freezing but not conditioned changes in arterial pressure. Ibotenic acid injected into the rostral CG reduced neither the arterial pressure nor the freezing response. Injection of ibotenic acid in the caudal CG, like electrolytic lesions of the rostral CG, disrupted the freezing, but not the arterial pressure response. Injection of ibotenic acid into the BNST had no effect on either response. These data demonstrate that neurons in the LH are involved in the autonomic, but not the behavioral, conditioned response pathway, whereas neurons in the caudal CG are involved in the behavioral, but not the autonomic, pathway. Different efferent projections of the central amygdala thus appear to mediate the behavioral and autonomic concomitants of conditioned fear.
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Connections from the central nucleus of the amygdala to the periaqueductal grey are responsible for behavioural aspects of the defence cascade.
“However, connections from the central nucleus of the amygdala (CE) to the periaqueductal grey (PAG) [47] are responsible for behavioural aspects of the defence cascade.”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [47]
The Conclusion (page unavailable) says the findings are consistent with the hypothesis that central-amygdala projections to the midbrain central gray mediate conditioned emotional behavior. The Midbrain central gray lesions section reports reduced conditioned freezing after caudal lesions. The source supports a role in this behavioral fear response, but the claim states the connection’s responsibility for behavioral aspects of the broader defence cascade more definitively than the paper does. (LLM, conf=0.82)
Experimental — accuracy not yet measuredActivation 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 [24]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDirect projections from the amygdala and limbic forebrain activate specific areas within the LPAG to produce these basic patterns, which control not only limb muscles but also laryngeal muscles resulting in snarling, growling, and howling.
“Direct projections from the amygdala and limbic forebrain activate specific areas within the LPAG to produce these basic patterns, which control not only limb muscles but also laryngeal muscles resulting in snarling, growling, and howling.24,48,49”
From Fear and the Defense Cascade (2015) · cites this paper as [24]
The amygdala–central gray behavioral conditioned response pathway section (page unavailable in our copy) describes projections from the limbic forebrain, including the central amygdala, through the central gray toward spinal motor systems involved in fear behavior. It does not establish activation of specific LPAG areas or describe laryngeal muscle control, snarling, growling, or howling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFlight or fight is the sum total of distinct components activated concurrently: a somatomotor component, a visceromotor component, and a pain-modulation component.
“Studies suggest that flight or fight is the sum total of distinct components activated concurrently: a somatomotor (skeletal muscle) component, a visceromotor (autonomic) component, and a pain-modulation component (see Figures 1 and 2).24,45,46”
From Fear and the Defense Cascade (2015) · cites this paper as [24]
The section on conditioned fear-response pathways (page unavailable) describes defensive behavior accompanied by autonomic changes and distinguishes freezing from cardiovascular responses. It does not establish a pain-modulation component of the response or say that all three components are activated concurrently; its discussion of pain sensitivity concerns whether that could explain a lesion result. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAll defense responses in the animal model of the defense cascade-arousal, freezing, flight or fight, tonic immobility, collapsed immobility, and quiescent immobility-are responses to threat mediated by neural circuits involving the extended amygdala, hypothalamus, periaqueductal gray, ventral pontine tegmentum, ventral and dorsal medulla, and spinal cord.
“All defense responses in the animal model of the defense cascade—arousal, freezing, flight or fight, tonic immobility, collapsed immobility, and quiescent immobility—are responses to threat mediated by neural circuits involving the extended amygdala, hypothalamus, periaqueductal gray (PAG), ventral pontine tegmentum, ventral and dorsal medulla, and spinal cord.22–25”
From Fear and the Defense Cascade (2015) · cites this paper as [24]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
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 [24]
The discussion of defense-response pathways says the central gray is involved in defensive behavior, and the discussion of conditioned fear describes it as a possible link to motor systems. The paper does not identify the lateral periaqueductal gray as mediating flight or fight or attribute attack, running, treading, or burying to it; its lesion findings concern conditioned freezing. (LLM, conf=0.76)
Experimental — accuracy not yet measuredFreezing depends on amygdala projections to the brainstem (periaqueductal grey) in rodents.
“Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey).”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [47]
The amygdala has been implicated in both threat learning and threat extinction processes.
“For thirty years, the amygdala has been implicated in both threat learning [48] and threat extinction [49] processes.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [48]
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- Authors
- LeDoux, J., Iwata, J., Cicchetti, P., & Reis, D.
- Affiliations
- Cornell University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1988-07-01
- Volume
- 8
- Issue
- 7
- Pages
- 2517-2529
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6569498
- OpenAlex
- W1738778520
- Cited by
- 1,580
- References
- 4
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 35 · 2023: 35 · 2022: 40 · 2021: 39 · 2020: 52 · 2019: 64 · 2018: 59 · 2017: 53 · 2016: 64 · 2015: 68 · 2014: 56 · 2013: 55 · 2012: 49
- FWCI
- 11.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (HL-18974)
- National Institute of Mental Health (MH38774)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- central amygdala, fear conditioning, classical fear conditioning, lateral hypothalamus, periaqueductal gray, bed nucleus of the stria terminalis, freezing behavior, autonomic responses, fear extinction, ibotenic acid lesions, efferent projections
- MeSH terms
- Amygdala, Animals, Autonomic Nervous System, Behavior, Animal, Conditioning, Classical, Fear, Hypothalamus, Male, Mesencephalon, Synaptic Transmission, Periaqueductal Gray, Rats, Inbred Strains, Thalamus, Rats
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