Abstract
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.