The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Behavioral State Instability in Orexin Knock-Out Mice
Open accessAbstract
Narcolepsy is caused by a lack of orexin (hypocretin), but the physiologic process that underlies the sleepiness of narcolepsy is unknown. Using orexin knock-out (KO) mice as a model of narcolepsy, we critically tested the three leading hypotheses: poor circadian control of sleep and wakefulness, inadequate activation of arousal regions, or abnormal sleep homeostasis. Compared with wild-type (WT) littermates, orexin KO mice had essentially normal amounts of sleep and wake, but wake and non-rapid eye movement (NREM) bouts were very brief, with many more transitions between all behavioral states. In constant darkness, orexin KO mice had normal amplitude and timing of sleep-wake rhythms, providing no evidence for disordered circadian control. When placed in a new, clean cage, both groups of mice remained awake for ∼45 min, demonstrating that, even in the absence of orexin, fundamental arousal regions can be engaged to produce sustained wakefulness. After depriving mice of sleep for 2-8 hr, orexin KO mice recovered their NREM and rapid eye movement sleep deficits at comparable rates and to the same extent as WT mice, with similar increases in EEG delta power, suggesting that their homeostatic control of sleep is normal. These experiments demonstrate that the fragmented wakefulness of orexin deficiency is not a consequence of abnormal sleep homeostasis, poor circadian control, or defective fundamental arousal systems. Instead, the fragmented behavior of orexin KO mice may be best described as behavioral state instability, with apparently low thresholds to transition between states.
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Cites
Neurons containing hypocretin (orexin) project to multiple neuronal systems
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Narcolepsy in orexin Knockout Mice
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Self-citationDijk, D., & Czeisler, C. (1995) · The Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03526.1995 · Cited by 1,356
Fos Expression in Orexin Neurons Varies with Behavioral State
Estabrooke, I. V., McCarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., Saper, C. B., & Scammell, T. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01656.2001 · Cited by 654
Self-citationA neural circuit for circadian regulation of arousal
Aston-Jones, G., Chen, S., Zhu, Y., & Oshinsky, M. L. (2001) · Nature Neuroscience · doi:10.1038/89522 · Cited by 632
Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms
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Self-citationIdentification of sleep-promoting neurons in vitro
Gallopin, T., Fort, P., Eggermann, E., Cauli, B., Luppi, P.-H., Rossier, J., Audinat, E., Mühlethaler, M., & Serafin, M. (2000) · Nature · doi:10.1038/35010109 · Cited by 504
Cited by
Hypothalamic regulation of sleep and circadian rhythms
Saper, C. B., Scammell, T. E., & Lu, J. (2005) · Nature · doi:10.1038/nature04284 · Cited by 2,804
Self-citationControl of sleep and wakefulness
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Self-citationHypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish
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Tranah, G. J., Blackwell, T., Stone, K. L., Ancoli‐Israel, S., Paudel, M. L., Ensrud, K. E., Cauley, J. A., Redline, S., Hillier, T. A., Cummings, S. R., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22468 · Cited by 525
Metadata
- Authors
- Mochizuki, T., Crocker, A., McCormack, S., Yanagisawa, M., Sakurai, T., & Scammell, T. E.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-07-14
- Volume
- 24
- Issue
- 28
- Pages
- 6291-6300
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2115070641
- Cited by
- 397
- References
- 7
- FWCI
- 9.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Mochizuki, T., Crocker, A., McCormack, S., Yanagisawa, M., Sakurai, T., & Scammell, T. E. (2004). Behavioral State Instability in Orexin Knock-Out Mice. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.0586-04.2004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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