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Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems
Open accessAbstract
The novel neuropeptides called hypocretins (orexins) have recently been identified as being localized exclusively in cell bodies in a subregion of the tuberal part of the hypothalamus. The structure of the hypocretins, their accumulation in vesicles of axon terminals, and their excitatory effect on cultured hypothalamic neurons suggest that the hypocretins function in intercellular communication. To characterize these peptides further and to help understand what physiological functions they may serve, we undertook an immunohistochemical study to examine the distribution of preprohypocretin-immunoreactive neurons and fibers in the rat brain. Preprohypocretin-positive neurons were found in the perifornical nucleus and in the dorsal and lateral hypothalamic areas. These cells were distinct from those that express melanin-concentrating hormone. Although they represent a restricted group of cells, their projections were widely distributed in the brain. We observed labeled fibers throughout the hypothalamus. The densest extrahypothalamic projection was found in the locus coeruleus. Fibers were also seen in the septal nuclei, the bed nucleus of the stria terminalis, the paraventricular and reuniens nuclei of the thalamus, the zona incerta, the subthalamic nucleus, the central gray, the substantia nigra, the raphe nuclei, the parabrachial area, the medullary reticular formation, and the nucleus of the solitary tract. Less prominent projections were found in cortical regions, central and anterior amygdaloid nuclei, and the olfactory bulb. These results suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep-waking cycle.
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“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 Peyron et al., 1998
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Self-citation
Metadata
- Authors
- Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., & Kilduff, T. S.
- Affiliations
- Stanford University (US)
- Scripps Research Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-12-01
- Volume
- 18
- Issue
- 23
- Pages
- 9996-10015
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793310
- OpenAlex
- W1627229807
- Cited by
- 3,466
- References
- 49
- Citations by year
- 2026: 48 · 2025: 88 · 2024: 102 · 2023: 123 · 2022: 128 · 2021: 122 · 2020: 144 · 2019: 111 · 2018: 146 · 2017: 145 · 2016: 157 · 2015: 156 · 2014: 183 · 2013: 169 · 2012: 182
- FWCI
- 36.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- 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 (R01NS034887, 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 › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- orexin, hypothalamic neurons, neuronal projections, melanin-concentrating hormone, locus coeruleus, septal nuclei, bed nucleus of the stria terminalis, thalamic nuclei, raphe nuclei, parabrachial area, medullary reticular formation, nucleus tractus solitarius, sleep-wake cycle, blood pressure regulation, neuroendocrine regulation, thermoregulation
- MeSH terms
- Orexins, Animals, Antibody Specificity, Blood Pressure, Brain Chemistry, Carrier Proteins, Dendrites, Eating, Male, Microscopy, Electron, Nerve Fibers, Neurons, Afferent, Neurons, Efferent, Neuropeptides, Rats, Wistar, Neurotransmitter Agents, Intracellular Signaling Peptides and Proteins, Rats
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