The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
Open accessAbstract
We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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The lateral hypothalamic area contains hypocretin/orexin neurons, which appear to play a critical role in arousal and probably reward.
“Recent data suggest that the lateral hypothalamic area contains hyporcretin/orexin (de Lecea et al., 1998, Sakurai et al., 1998) neurons (Peyron et al., 1998), which appear to play a critical role in arousal (Siegel, 2004; Saper et al., 2005) and probably reward (Harris et al., 2005; Harris and Aston-Jones, 2006).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as de Lecea et al., 1998
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Ghrelin-Induced Food Intake Is Mediated via the Orexin Pathway
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- Authors
- de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., van den Pol, A. N., Bloom, F. E., Gautvik, K. M., & Sutcliffe, J. G.
- Affiliations
- Departments of Molecular Biology and Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; Center for Sleep and Circadian Neurobiology, Stanford University, Stanford, CA 94305; Department of Neurosurgery, Yale University, New Haven, CT 06520; Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway; and The Jackson Laboratory, Bar Harbor, ME 04609
- Scripps Research Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-01-06
- Volume
- 95
- Issue
- 1
- Pages
- 322-327
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18213
- OpenAlex
- W2152211310
- Cited by
- 3,878
- References
- 46
- Citations by year
- 2026: 83 · 2025: 126 · 2024: 108 · 2023: 123 · 2022: 156 · 2021: 133 · 2020: 137 · 2019: 133 · 2018: 170 · 2017: 159 · 2016: 159 · 2015: 173 · 2014: 208 · 2013: 186 · 2012: 188
- FWCI
- 55.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Fondation Fyssen
- Norges Forskningsråd
- National Institutes of Health (5r01ns033396-03, 5p01ag011084-05)
- National Institute on Aging (AG-11084)
- National Institute of General Medical Sciences (GM-32355, R01GM032355)
- National Institute of Neurological Disorders and Stroke (NS33396)
- Army Research Office
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- orexin, hypothalamus, hypothalamic neurons, secretin, neuropeptides, neurotransmitters, hypothalamic projections, brainstem, thalamus
- MeSH terms
- Orexins, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Chromosomes, Homeostasis, Hypothalamus, Posterior, Male, Molecular Sequence Data, Neurons, Neuropeptides, Protein Precursors, Secretin, Synaptic Vesicles, Consensus Sequence, Rats, Wistar, Neurotransmitter Agents, Intracellular Signaling Peptides and Proteins, Mice, Rats
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