Changes in the composition of brain interstitial ions control the sleep-wake cycle

Fengfei Ding; John O'Donnell; Qiwu Xu; Ning Kang; Nanna Goldman; Maiken Nedergaard

doi:10.1126/science.aad4821

Changes in the composition of brain interstitial ions control the sleep-wake cycle

Fengfei Ding, John O'Donnell, Qiwu Xu, Ning Kang, Nanna Goldman, Maiken Nedergaard

143 Citationer (Scopus)

Abstract

Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K⁺ concentration ([K⁺]_e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K⁺]_e concomitant with decreases in [Ca²⁺]_e, [Mg²⁺]_e, [H⁺]_e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K⁺]_e while increasing [Ca²⁺]_e, [Mg²⁺]_e, and [H⁺]_e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.

Originalsprog	Engelsk
Tidsskrift	Science
Vol/bind	352
Udgave nummer	6285
Sider (fra-til)	550-555
Antal sider	6
ISSN	0036-8075
DOI	https://doi.org/10.1126/science.aad4821
Status	Udgivet - 29 apr. 2016

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abstract = "Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.",

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author = "Fengfei Ding and John O'Donnell and Qiwu Xu and Ning Kang and Nanna Goldman and Maiken Nedergaard",

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T1 - Changes in the composition of brain interstitial ions control the sleep-wake cycle

AU - Ding, Fengfei

AU - O'Donnell, John

AU - Xu, Qiwu

AU - Kang, Ning

AU - Goldman, Nanna

AU - Nedergaard, Maiken

PY - 2016/4/29

Y1 - 2016/4/29

N2 - Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.

AB - Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.

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KW - Calcium

KW - Cations

KW - Cerebral Cortex

KW - Electroencephalography

KW - Magnesium

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Neurons

KW - Neurotransmitter Agents

KW - Potassium

KW - Receptors, AMPA

KW - Sleep

KW - Sodium Channel Blockers

KW - Tetrodotoxin

KW - Wakefulness

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1126/science.aad4821

DO - 10.1126/science.aad4821

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ER -

Changes in the composition of brain interstitial ions control the sleep-wake cycle

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