Identification of sleep-promoting neurons in vitro
Open accessAbstract
The neurons responsible for the onset of sleep are thought to be located in the preoptic area and more specifically, in the ventrolateral preoptic nucleus (VLPO). Here we identify sleep-promoting neurons in vitro and show that they represent an homogeneous population of cells that must be inhibited by systems of arousal during the waking state. We find that two-thirds of the VLPO neurons are multipolar triangular cells that show a low-threshold spike. This proportion matches that of cells active during sleep in the same region. We then show, using single-cell reverse transcriptase followed by polymerase chain reaction, that these neurons probably contain gamma-aminobutyric acid (GABA). We also show that these neurons are inhibited by noradrenaline and acetylcholine, both of which are transmitters of wakefulness. As most of these cells are also inhibited by serotonin but unaffected by histamine, their overall inhibition by transmitters of wakefulness is in agreement with their relative inactivity during waking with respect to sleep. We propose that the reciprocal inhibitory interaction of such VLPO neurons with the noradrenergic, serotoninergic and cholinergic waking systems to which they project is a key factor for promoting sleep.
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Fatigue in individuals with hypothalamic syndrome could potentially be related to disordered signaling from GABAergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei.
“Commonly reported fatigue (72, 73) could potentially be related to disordered signaling from γ-aminobutyric acid (GABA)-ergic neurons in the suprachiasmatic, ventrolateral, and preoptic nuclei (74, 75).”
From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [74]
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- Authors
- Gallopin, T., Fort, P., Eggermann, E., Cauli, B., Luppi, P.-H., Rossier, J., Audinat, E., Mühlethaler, M., & Serafin, M.
- Affiliations
- University of Geneva (CH)
- Centre National de la Recherche Scientifique (FR)
- ESPCI Paris (FR)
- Corresponding author
- Mühlethaler, Michel
- Venue
- Nature
- Published
- 2000-04
- Volume
- 404
- Issue
- 6781
- Pages
- 992-995
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1612453552
- Cited by
- 504
- References
- 2
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 9 · 2023: 16 · 2022: 13 · 2021: 19 · 2020: 6 · 2019: 24 · 2018: 19 · 2017: 15 · 2016: 18 · 2015: 24 · 2014: 18 · 2013: 17 · 2012: 24
- FWCI
- 14.10
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- 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 › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep-promoting neurons, ventrolateral preoptic nucleus, preoptic area, sleep onset, GABAergic neurons, norepinephrine, acetylcholine, serotonin, histamine, wakefulness, neuronal inhibition, low-threshold spikes, multipolar neurons, reciprocal inhibition
- MeSH terms
- Action Potentials, Animals, Carbachol, Choline O-Acetyltransferase, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Histamine, Neural Inhibition, Neurons, Norepinephrine, Preoptic Area, Serotonin, Sleep, Rats, In Vitro Techniques
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