Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2

Rosin, Diane L.; Weston, Matthew C.; Sevigny, Charles P.; Stornetta, Ruth L.; Guyenet, Patrice G.

doi:10.1002/cne.10860

Cited by 252Sleep and Wakefulness ResearchNeuroscience of respiration and sleepNeuroscience and Neuropharmacology Research

Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2

Rosin, Diane L., Weston, Matthew C., Sevigny, Charles P., Stornetta, Ruth L., Guyenet, Patrice G.·2003·Journal of Comparative Neurology

DOI 10.1002/cne.10860

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Abstract

Initially recognized for their importance in control of appetite, orexins (also called hypocretins) are neuropeptides that are also involved in regulating sleep, arousal, and cardiovascular function. Loss of orexin appears to be the primary cause of narcolepsy. Cells expressing the orexins are restricted to a discrete region of the hypothalamus, but their terminal projections are widely distributed throughout the brain. With the diversity of function and broad distribution of orexin terminals, it is not known whether the orexin cells constitute a homogeneous population. Because orexins produce neuroexcitatory effects, we hypothesized that orexin-containing neurons are glutamatergic. In the present study we used digoxigenin-labeled cRNA probes for the vesicular glutamate transporters, VGLUT1 and VGLUT2, for in situ hybridization studies in combination with immunohistochemical detection of orexin cell bodies in the hypothalamus. In general, cells in the hypothalamus expressed low levels of the vesicular glutamate transporters relative to other areas of the forebrain, such as the cortex and thalamus. Light labeling for VGLUT2 mRNA was detected in about 50% of the orexin-immunoreactive neurons, and a much smaller percentage (approximately 13%) of orexin-immunoreactive cells was found to express VGLUT1. Despite the fact that intense labeling for GAD67 mRNA was found in a large number of cells throughout the hypothalamus, none of the orexin-immunoreactive cells was found to be GABAergic. These findings, showing that many of the orexin neurons are glutamatergic, are consistent with the neuroexcitatory effects of orexin but suggest that another neurochemical phenotype may define the remaining subset of orexin neurons.

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VGLUT2 is highly expressed in the hypothalamus, including OX neurons.
“It is known that glutamate transporters, particularity VGLUT2, are highly expressed in the hypothalamus, including OX neurons (Ziegler et al., 2002, Rosin et al., 2003)”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Rosin et al., 2003

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Untitled work
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Control of sleep and wakefulness
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Authors: Rosin, D. L., Weston, M. C., Sevigny, C. P., Stornetta, R. L., & Guyenet, P. G.
Affiliations: University of Virginia Health System (US)
University of Virginia (US)
Corresponding author: Rosin, Diane L.
ORCID: Rosin, Diane L.
Weston, Matthew C.
Sevigny, Charles P.
Stornetta, Ruth L.
Guyenet, Patrice G.
Venue: Journal of Comparative Neurology
Publisher: Wiley
Published: 2003-09-10
Volume: 465
Issue: 4
Pages: 593-603
ISSN: 0021-9967 (ISSN-L)
1096-9861
DOI: 10.1002/cne.10860
OpenAlex: W2138262820
Cited by: 252
References: 83
Citations by year: 2026: 7 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 7 · 2019: 12 · 2018: 14 · 2017: 20 · 2016: 17 · 2015: 16 · 2014: 14 · 2013: 11 · 2012: 14
FWCI: 4.08
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Comparative Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-28785)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: orexin, hypothalamic neurons, vesicular glutamate transporter, VGLUT1, VGLUT2, glutamatergic neurons, GABAergic neurons, GAD67, narcolepsy, neuronal phenotype
MeSH terms: Orexins, Animals, Appetite Regulation, Carrier Proteins, Efferent Pathways, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Hypothalamus, Isoenzymes, Male, Narcolepsy, Synaptic Transmission, Neurons, Neuropeptides, RNA, Messenger, Rats, Sprague-Dawley, Glutamic Acid, Membrane Transport Proteins, Vesicular Transport Proteins, Intracellular Signaling Peptides and Proteins, Vesicular Glutamate Transport Protein 1, Vesicular Glutamate Transport Protein 2, Rats

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Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2

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