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.
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Udgave nummer40
Antal sider9
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
ACKNOWLEDGMENTS. A.G.D. is a recipient of a Lundbeck Foundation PhD Fellowship (R263-2017-4062), the project also received additional funding from the Lundbeck Foundation (R155-2016-552), Novo Nordisk Foundation

Funding Information:
(NNFOC0058058 and NNF13O0004258), and R01AT012312RF1AG057575, R01AT011439,the U.S.Army under award MURIW911NF1910280 and the Simon and Adelson foundations.We would like to thank Dan Xue for the graphical design.

Publisher Copyright:
© 2023 the Author(s).

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