Local extracellular K+ in cortex regulates norepinephrine levels, network state, and behavioral output

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Extracellular potassium concentration ([K+]e) is known to increase as a function of arousal. [K+]e is also a potent modulator of transmitter release. Yet, it is not known whether [K+]e is involved in the neuromodulator release associated with behavioral transitions. We here show that manipulating [K+]e controls the local release of monoaminergic neuromodulators, including norepinephrine (NE), serotonin, and dopamine. Imposing a [K+]e increase is adequate to boost local NE levels, and conversely, lowering [K+]e can attenuate local NE. Electroencephalography analysis and behavioral assays revealed that manipulation of cortical [K+]e was sufficient to alter the sleep-wake cycle and behavior of mice. These observations point to the concept that NE levels in the cortex are not solely determined by subcortical release, but that local [K+]e dynamics have a strong impact on cortical NE. Thus, cortical [K+]e is an underappreciated regulator of behavioral transitions.

Original languageEnglish
Article numbere2305071120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number40
Number of pages9
ISSN0027-8424
DOIs
Publication statusPublished - 2023

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© 2023 the Author(s).

    Research areas

  • cortical state change, ions, neuromodulators

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