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Identification of preoptic sleep neurons using retrograde labelling and gene profiling
Open accessAbstract
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.
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“the ventrolateral preoptic nucleus (VLPO) contains neurons that are sleep-active [96, 97]”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [97]
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Metadata
- Authors
- Chung, S., Weber, F., Zhong, P., Tan, C. L., Nguyen, T. N., Beier, K. T., Hörmann, N., Chang, W.-C., Zhang, Z., Do, J. P., Yao, S., Krashes, M. J., Tasic, B., Cetin, A., Zeng, H., Knight, Z. A., Luo, L., & Dan, Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Allen Institute for Brain Science (US)
- National Institutes of Health (US)
- Corresponding author
- Dan, Yang
- ORCID
- Venue
- Nature
- Published
- 2017-05
- Volume
- 545
- Issue
- 7655
- Pages
- 477-481
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5554302
- OpenAlex
- W2616271045
- Cited by
- 317
- References
- 44
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 32 · 2023: 28 · 2022: 27 · 2021: 31 · 2020: 26 · 2019: 40 · 2018: 69 · 2017: 10
- FWCI
- 22.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1dp2dk109533-01)
- National Institute of Mental Health (U01MH105982)
- National Institute on Drug Abuse (F32DA038913, K99DA041445)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2-DK109533, R01DK106399)
- National Institute of Neurological Disorders and Stroke (R01NS094781)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- preoptic area, hypothalamus, sleep regulation, sleep-promoting neurons, GABAergic neurons, tuberomammillary nucleus, retrograde tracing, optogenetics, single-cell RNA sequencing, translating ribosome affinity purification, cholecystokinin, corticotropin-releasing factor
- MeSH terms
- Channelrhodopsins, Animals, Cholecystokinin, Corticotropin-Releasing Hormone, Female, Hypothalamic Area, Lateral, Male, Neurons, Preoptic Area, Ribosomes, Sleep, Wakefulness, Tachykinins, Biomarkers, Proto-Oncogene Proteins c-fos, Sequence Analysis, RNA, Chloride Channels, Mice, Neuroanatomical Tract-Tracing Techniques, Single-Cell Analysis, GABAergic Neurons, Transcriptome, Optogenetics
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