Amygdala lesions reduce cataplexy in orexin knock-out mice
Open accessAbstract
Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.
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Environmental enrichment reduces anxiety and promotes positive affective states in rodents.
“Environmental enrichment has previously been shown to reduce anxiety and promote positive affective states in rodents [10–12], making it a suitable paradigm to study long-term positive olfactory memory.”
From Positive early-life olfactory memory is rooted in the olfactory bulb and triggers large-scale changes beyond the olfactory system (2026) · cites this paper as [12]
The Results section reports that a running wheel and chocolate increased cataplexy in orexin knock-out mice and describes these as stimuli associated with positive emotions. Our copy does not address whether environmental enrichment reduces anxiety or promotes positive affective states in rodents; searches for environmental enrichment and anxiety found no supporting passage. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAn enriched playful environment enhances animal well-being.
“an enriched playful environment, which is reported to enhance animal well-being [10–12].”
From Positive early-life olfactory memory is rooted in the olfactory bulb and triggers large-scale changes beyond the olfactory system (2026) · cites this paper as [12]
The Results section reports that a running wheel and chocolate increased cataplexy and wakefulness in orexin knock-out mice. The Discussion describes these stimuli as presumably triggering positive affect, but neither section assesses whether an enriched playful environment enhances animal well-being. Searches for enrichment, play, welfare, and well-being found no passage establishing that claim. (LLM, conf=0.76)
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- Authors
- Burgess, C. R., Oishi, Y., Mochizuki, T., Peever, J. H., & Scammell, T. E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Toronto (CA)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-06-05
- Volume
- 33
- Issue
- 23
- Pages
- 9734-9742
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3704329
- OpenAlex
- W2150993098
- Cited by
- 108
- References
- 72
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 11 · 2014: 8 · 2013: 3
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Heart, Lung, and Blood Institute (P01HL095491)
- National Institute of Neurological Disorders and Stroke (R01NS055367, NS-055367)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- cataplexy, amygdala, orexin knockout mice, narcolepsy, muscle atonia, emotional arousal, GABAergic neurons, central amygdala, ventrolateral periaqueductal gray, pontine tegmentum, locus coeruleus, dorsal raphe nucleus, excitotoxic lesions, sleep-wake behavior
- MeSH terms
- Orexins, Amygdala, Animals, Cataplexy, Electroencephalography, Male, Mice, Inbred C57BL, Neuropeptides, Mice, Knockout, Intracellular Signaling Peptides and Proteins, Mice
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