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

Research output: Contribution to journalArticlepeer-review

250 Scopus citations


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.

Original languageEnglish
Pages (from-to)550-555
Number of pages6
Issue number6285
StatePublished - Apr 29 2016


Dive into the research topics of 'Changes in the composition of brain interstitial ions control the sleep-wake cycle'. Together they form a unique fingerprint.

Cite this