Research Article

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

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Science  29 Apr 2016:
Vol. 352, Issue 6285, pp. 550-555
DOI: 10.1126/science.aad4821

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Sleep induction through ion changes

How do we switch from sleep to arousal and back? Ding et al. found that a combination of modulatory neurotransmitters influenced the levels of extracellular ions in the brain (see the Perspective by Landolt and Holst). This influence was not driven by changes in local neuronal firing, suggesting direct effects of the neuromodulators on extracellular ion composition. However, these changes in interstitial ion levels could switch a brain from wakefulness to sleep. Changes in extracellular ions may thus be a cause, rather than a consequence, of sleep/wake-dependent changes in neuronal activity.

Science, this issue p. 550; see also p. 517

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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