Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states
Open accessAbstract
Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.
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During REM sleep, neuronal ATP levels declined sharply.
“This was accompanied by elevated astrocytic pyruvate; paradoxically, however, neuronal ATP levels declined sharply.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [31]
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- Authors
- Natsubori, A., Tsunematsu, T., Karashima, A., Imamura, H., Kabe, N., Trevisiol, A., Hirrlinger, J., Kodama, T., Sanagi, T., Masamoto, K., Takata, N., Nave, K.-A., Matsui, K., Tanaka, K. F., & Honda, M.
- Affiliations
- Tokyo Metropolitan Institute of Medical Science (JP)
- Tohoku University (JP)
- Tohoku Institute of Technology (JP)
- Kyoto University (JP)
- Max Planck Institute of Experimental Medicine (DE)
- University of Electro-Communications (JP)
- Keio University (JP)
- Corresponding author
- Natsubori, Akiyo
- ORCID
- Venue
- Communications Biology
- Published
- 2020-09-07
- Volume
- 3
- Issue
- 1
- Pages
- 491-491
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC7477120
- OpenAlex
- W3083336922
- Cited by
- 54
- References
- 70
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 9
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Meiji Yasuda Life Foundation of Health and Welfare
- Japan Society for the Promotion of Science (19H05027, 20H05896, 17K00932, 20H03221, 20H05894, 20H05047, 19K06944, 18K14756)
- Precursory Research for Embryonic Science and Technology (JPMJPR1887)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- intracellular ATP, sleep-wake states, cortical excitatory neurons, neuronal energy metabolism, REM sleep, cerebral hemodynamics, neuronal activation, energy homeostasis, mouse brain
- MeSH terms
- Adenosine Triphosphate, Animals, Cerebral Cortex, Cerebrovascular Circulation, Cortical Synchronization, Cytosol, Electric Stimulation, Mice, Inbred C57BL, Neurons, Sleep, Wakefulness, Intracellular Space, Optical Imaging
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