000 02464 am a22003133u 4500
042 _adc
100 1 0 _aAlfonsa, Hannah
_eauthor
_92084
700 1 0 _aBurman, Richard J.
_eauthor
_92085
700 1 0 _aBrodersen, Paul J. N.
_eauthor
_92086
700 1 0 _aNewey, Sarah E.
_eauthor
_92087
700 1 0 _aMahfooz, Kashif
_eauthor
_92088
700 1 0 _aYamagata, Tomoko
_eauthor
_92089
700 1 0 _aPanayi, Marios C.
_eauthor
_92090
700 1 0 _aBannerman, David M.
_eauthor
_92091
700 1 0 _aVyazovskiy, Vladyslav V.
_eauthor
_92092
700 1 0 _aAkerman, Colin J.
_eauthor
_92093
245 0 0 _aIntracellular chloride regulation mediates local sleep pressure in the cortex
260 _c2023-01.
500 _a/pmc/articles/PMC7614036/
500 _a/pubmed/36510112
520 _aExtended wakefulness is associated with reduced performance and the build-up of sleep pressure. In the cortex, this manifests as changes in network activity. These changes show local variation depending on the waking experience, and their underlying mechanisms represent targets for overcoming the effects of tiredness. Here we reveal a central role for intracellular chloride regulation, which sets the strength of postsynaptic inhibition via GABA(A) receptors in cortical pyramidal neurons. Wakefulness results in depolarizing shifts in the equilibrium potential for GABA(A) receptors, reflecting local activity-dependent processes during waking, and involving changes in chloride cotransporter activity. These changes underlie electrophysiological and behavioral markers of local sleep pressure within cortex - including the levels of slow-wave activity during non-rapid eye movement sleep - as well as low-frequency oscillatory activity and reduced performance levels in the sleep-deprived awake state. These findings identify chloride regulation as a crucial link between sleep-wake history, cortical activity and behavior.
540 _a
540 _ahttps://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Neurosci
856 4 1 _uhttp://dx.doi.org/10.1038/s41593-022-01214-2
_zConnect to this object online.
999 _c872
_d872