Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states

Akiyo Natsubori, Tomomi Tsunematsu, Akihiro Karashima, Hiromi Imamura, Naoya Kabe, Andrea Trevisiol, Johannes Hirrlinger, Tohru Kodama, Tomomi Sanagi, Kazuto Masamoto, Norio Takata, Klaus Armin Nave, Ko Matsui, Kenji F. Tanaka, Makoto Honda

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Article number491
JournalCommunications biology
Issue number1
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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