Properties of REM sleep alterations with epilepsy
Open accessAbstract
It is usually assumed that individuals rest during sleep. However, coordinated neural activity that presumably requires high energy consumption is increased during REM sleep. Here, using freely moving male transgenic mice, the local brain environment and astrocyte activity during REM sleep were examined using the fibre photometry method with an optical fibre inserted deep into the lateral hypothalamus, a region that is linked with controlling sleep and metabolic state of the entire brain. Optical fluctuations of endogenous autofluorescence of the brain parenchyma or fluorescence of sensors for Ca2+ or pH expressed in astrocytes were examined. Using a newly devised method for analysis, changes in cytosolic Ca2+ and pH in astrocytes and changes in the local brain blood volume (BBV) were extracted. On REM sleep, astrocytic Ca2+ decreases, pH decreases (acidification) and BBV increases. Acidification was unexpected, as an increase in BBV would result in efficient carbon dioxide and/or lactate removal, which leads to alkalinization of the local brain environment. Acidification could be a result of increased glutamate transporter activity due to enhanced neuronal activity and/or aerobic metabolism in astrocytes. Notably, optical signal changes preceded the onset of the electrophysiological property signature of REM sleep by ∼20–30 s. This suggests that changes in the local brain environment have strong control over the state of neuronal cell activity. With repeated stimulation of the hippocampus, seizure response gradually develops through kindling. After a fully kindled state was obtained with multiple days of stimuli, the optical properties of REM sleep at the lateral hypothalamus were examined again. Although a negative deflection of the detected optical signal was observed during REM sleep after kindling, the estimated component changed. The decrease in Ca2+ and increase in BBV were minimal, and a large decrease in pH (acidification) emerged. This acidic shift may trigger an additional gliotransmitter release from astrocytes, which could lead to a state of hyperexcitable brain. As the properties of REM sleep change with the development of epilepsy, REM sleep analysis may serve as a biomarker of epileptogenesis severity. REM sleep analysis may also predict whether a specific REM sleep episode triggers post-sleep seizures.
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REM sleep is marked by a pronounced increase in brain blood volume.
“In contrast, REM sleep was marked by a pronounced increase in BBV, originating in the posterior cortex and slowly propagating across the brain.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [4]
The Discussion reports a prominent increase in local brain blood volume during REM sleep in the lateral hypothalamus of mice. The cited paper does not establish the citing sentence’s further claim that the increase originates in the posterior cortex and slowly propagates across the brain. (LLM, conf=0.88)
Experimental — accuracy not yet measuredFluorescence emitted from parenchymal cells is attenuated by overlying blood vessels, which appear as shadows in wide-field images.
“Our earlier studies showed that fluorescence emitted from parenchymal cells is attenuated by overlying blood vessels, which therefore appear as shadows in wide-field images2,4,36.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [4]
The 'Optical measurements of REM sleep with autofluorescence' section says increased blood-vessel volume near an optical fibre can obstruct detection of fluorescence from brain parenchyma, and reports a corresponding decrease in the measured signal. It does not describe overlying vessels appearing as shadows in wide-field images; its measurements use fibre photometry. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCerebral blood flow and BBV rise during REM sleep.
“Prior work has shown that cerebral blood flow and BBV rise during REM sleep4.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [4]
Astrocytic acidification during REM sleep has been reported in the lateral hypothalamus.
“Supporting this idea, astrocytic acidification during REM sleep has been reported in the lateral hypothalamus4.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [4]
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Reviewer #1 (Public Review): Plastic vasomotion entrainment
Sasaki, D., Imai, K., Ikoma, Y., et al. (2024) · eLife · doi:10.7554/elife.93721.1.sa2
Reviewer #3 (Public Review): Plastic vasomotion entrainment
Sasaki, D., Imai, K., Ikoma, Y., et al. (2024) · eLife · doi:10.7554/elife.93721.1.sa0
Author Response: Plastic vasomotion entrainment
Sasaki, D., Imai, K., Ikoma, Y., & Matsui, K. (2024) · eLife · doi:10.7554/elife.93721.1.sa4
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Sasaki, D., Imai, K., Ikoma, Y., & Matsui, K. (2024) · eLife · doi:10.7554/elife.93721.2
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Epilepsy as a Wilding of Sleep
Szűcs, A., & Halász, P. (2025) · Current Treatment Options in Neurology · doi:10.1007/s11940-024-00819-1
Abnormal Synchronization Between Cortical Delta Power and Ripples in Hippocampal Sclerosis
Iwata, T., Yanagisawa, T., Fukuma, R., Ikegaya, Y., Oshino, S., Tani, N., Khoo, H. M., Sugano, H., Iimura, Y., Suzuki, H., et al. (2025) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70032
Diurnal modulation of optogenetically evoked neural signals
Donen, Y., Ikoma, Y., & Matsui, K. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.104981 · Cited by 1 · see citing works
Self-citationVagal nerve stimulation induces vascular oscillations and enhances long-term learning
Chen, J. U., Ikoma, Y., & Matsui, K. (2026) · iScience · doi:10.1016/j.isci.2026.117413
Self-citationAlam, B. B., Mahmood, R., Nasir, S., Ishaq, A., Ghazala, S., & Jabeen, M. (2026) · Journal of Rawalpindi Medical College · doi:10.37939/jrmc.2984
- Authors
- Ikoma, Y., Takahashi, Y., Sasaki, D., & Matsui, K.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Matsui, Ko
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-03-03
- Volume
- 146
- Issue
- 6
- Pages
- 2431-2442
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W4323037385
- Cited by
- 33
- References
- 61
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 14 · 2023: 9
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Grant-in-Aid for Transformative Research Areas
- Grant-in-Aid for Scientific Research on Innovative Areas
- Grant-in-Aid for Scientific Research
- Grant-in-Aid for Young Scientists
- Research Foundation for Opto-Science and Technology
- NOVARTIS Foundation
- Takeda Science Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- REM sleep, epilepsy, astrocytes, lateral hypothalamus, kindling, epileptogenesis, gliotransmitter release, seizure prediction, biomarkers
- MeSH terms
- Animals, Calcium, Epilepsy, Male, Seizures, Sleep, Sleep, REM, Mice
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