Role of the extended amygdala in short-duration versus sustained fear: a tribute to Dr. Lennart Heimer
Abstract
The concept of the "extended amygdala", developed and explored by Lennart Heimer, Jose de Olmos, George Alheid, and their collaborators, has had an enormous impact on the field of neuroscience and on our own work. Measuring fear-potentiated startle test using conditioned stimuli that vary in length we suggest that the central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST(L)) are involved in short-term versus long-term fear responses we call phasic versus sustained fear, respectively. Outputs from the basolateral amygdala (BLA) activate the medial division of the CeA (CeA(M)) to very rapidly elicit phasic fear responses via CeA(M) projections to the hypothalamus and brainstem. The BLA also projects to the BNST(L), which together with other BNST(L) inputs from the lateral CeA (CeA(L)) initiate a slower developing, but sustained fear response, akin to anxiety. We hypothesize this occurs because the CeA(L) releases the peptide corticotropin releasing hormone (CRF) into the BNST(L) which facilitates the release of glutamate from BLA terminals. This activates the BNST(L) which projects to hypothalamic and brainstem areas similar to those innervated by the CeA(M) that mediate the specific signs of fear and anxiety. The generality of this idea is illustrated by selective studies looking at context conditioning, social defeat, drug withdrawal and stress induced reinstatement.
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The amygdala's function is detecting and controlling behavioural and physiological responses to immediate danger, while uncertain threats are processed by the bed nucleus of the stria terminalis (BNST).
“According to recent research, the amygdala's function is detecting and controlling the behavioural and physiological responses to immediate danger while the uncertain threats are processed by the bed nucleus of the stria terminalis (BNST; Walker and Davis 2008; Hammack et al . 2015) (Fig. 2).”
From Recent findings in the pathogenesis and treatment of fear and anxiety (2022) · cites this paper as Walker and Davis 2008
Rodent data suggest phasic fear responses rely on the central nucleus of the amygdala, which in humans is located in the dorsal part of the amygdala.
“Rodent data suggest that phasic fear responses rely on the central nucleus of the amygdala (CeA), which in humans is located in the dorsal part of the amygdala (Amunts et al., 2005)”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Walker and Davis, 2008
Sustained fear responses depend on the bed nucleus of the stria terminalis, located in the ventromedial basal forebrain and receiving input from the central nucleus of the amygdala and the basolateral amygdala complex.
“sustained fear responses are dependent on the bed nucleus of the stria terminalis (BNST), which is located in the ventromedial basal forebrain and receives input from the CeA and the more ventrally located basolateral amygdala complex (BLC) (Walker and Davis, 2008)”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Walker and Davis, 2008
It has been suggested that anterior insula might mediate cognitive aspects of worry.
“It has been suggested that anterior insula might mediate cognitive aspects of worry (Walker and Davis, 2008).”
From Phasic and sustained fear in humans elicits distinct patterns of brain activity (2011) · cites this paper as Walker and Davis, 2008
In the LN, these changes may directly affect fear conditioning, whereas changes in the BN may impact on hippocampal context learning, and involvement of the CE, ME and ABN suggests direct effects on the bed nucleus of the stria terminalis, speculatively impacting on sustained fear mechanisms.
“In the LN, these changes may directly affect fear conditioning, whereas changes in the BN may impact on hippocampal context learning, and involvement of the CE, ME and ABN suggests direct effects on the bed nucleus of the stria terminalis, speculatively impacting on sustained fear mechanisms.95, 96, 97, 98”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [96]
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References 142 · Cited by 231
- Authors
- Walker, D. L., & Davis, M.
- Affiliations
- Emory University (US)
- Corresponding author
- Walker, David L.
- ORCID
- Walker, David L.
- Venue
- Brain Structure and Function
- Published
- 2008-06-05
- Volume
- 213
- Issue
- 1-2
- Pages
- 29-42
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- OpenAlex
- W2166054235
- Cited by
- 231
- References
- 142
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 15 · 2019: 13 · 2018: 19 · 2017: 15 · 2016: 23 · 2015: 14 · 2014: 16 · 2013: 13 · 2012: 15
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Brain Structure and Function (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Emory University
- Neurosciences Foundation
- National Institutes of Health (5u19mh069056-10)
- National Institute of Mental Health (MH59906, MH-57250, R01MH057250, R01MH059906, MH 47840, MH069056)
- 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
- extended amygdala, central amygdala, bed nucleus of the stria terminalis, basolateral amygdala, corticotropin-releasing factor, fear-potentiated startle, anxiety, hypothalamus, brainstem, contextual conditioning, social defeat, drug withdrawal, stress-induced reinstatement
- MeSH terms
- Amygdala, Animals, Anxiety, Corticotropin-Releasing Hormone, Fear, Neural Pathways, Neurons, Septal Nuclei, Reflex, Startle, Stress, Psychological
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