{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:48:58Z","timestamp":1790765338077,"version":"4.1.0"},"reference-count":50,"publisher":"Society for Neuroscience","issue":"49","license":[{"start":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T00:00:00Z","timestamp":1496793600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2016,12,7]]},"abstract":"<jats:p>During non-rapid eye movement (NREM) sleep, cortical neurons alternate between ON periods of firing and OFF periods of silence. This bi-stability, which is largely synchronous across neurons, is reflected in the EEG as slow waves. Slow-wave activity (SWA) increases with wake duration and declines homeostatically during sleep, but the underlying mechanisms remain unclear. One possibility is neuronal \u201cfatigue\u201d: high, sustained firing in wake would force neurons to recover with more frequent and longer OFF periods during sleep. Another possibility is net synaptic potentiation during wake: stronger coupling among neurons would lead to greater synchrony and therefore higher SWA. Here, we obtained a comparable increase in sustained firing (6 h) in cortex by: (1) keeping mice awake by exposure to novel objects to promote plasticity and (2) optogenetically activating a local population of cortical neurons at wake-like levels during sleep. Sleep after extended wake led to increased SWA, higher synchrony, and more time spent OFF, with a positive correlation between SWA, synchrony, and OFF periods. Moreover, time spent OFF was correlated with cortical firing during prior wake. After local optogenetic stimulation, SWA and cortical synchrony decreased locally, time spent OFF did not change, and local SWA was not correlated with either measure. Moreover, laser-induced cortical firing was not correlated with time spent OFF afterward. Overall, these results suggest that high sustained firing per se may not be the primary determinant of SWA increases observed after extended wake.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>A long-standing hypothesis is that neurons fire less during slow-wave sleep to recover from the \u201cfatigue\u201d accrued during wake, when overall synaptic activity is higher than in sleep. This idea, however, has rarely been tested and other factors, namely increased cortical synchrony, could explain why sleep slow-wave activity (SWA) is higher after extended wake. We forced neurons in the mouse cortex to fire at high levels for 6 h in 2 different conditions: during active wake with exploration and during sleep. We find that neurons need more time OFF only after sustained firing in wake, suggesting that fatigue due to sustained firing alone is unlikely to account for the increase in SWA that follows sleep deprivation.<\/jats:p>","DOI":"10.1523\/jneurosci.1614-16.2016","type":"journal-article","created":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T17:05:10Z","timestamp":1481130310000},"page":"12436-12447","source":"Crossref","is-referenced-by-count":77,"title":["Why Does Sleep Slow-Wave Activity Increase After Extended Wake? Assessing the Effects of Increased Cortical Firing During Wake and Sleep"],"prefix":"10.1523","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0547-8842","authenticated-orcid":false,"given":"Alexander V.","family":"Rodriguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-7803","authenticated-orcid":false,"given":"Chadd M.","family":"Funk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-6681","authenticated-orcid":false,"given":"Vladyslav V.","family":"Vyazovskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5433-6349","authenticated-orcid":false,"given":"Yuval","family":"Nir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Tononi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-677X","authenticated-orcid":false,"given":"Chiara","family":"Cirelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2016,12,7]]},"reference":[{"key":"2023041803223505000_36.49.12436.1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-015-0176-7"},{"key":"2023041803223505000_36.49.12436.2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)00057-O"},{"key":"2023041803223505000_36.49.12436.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3607-05.2006"},{"key":"2023041803223505000_36.49.12436.4","first-page":"195","article-title":"A two process model of sleep regulation","volume":"1","author":"Borb\u00e9ly","year":"1982","journal-title":"Hum Neurobiol"},{"key":"2023041803223505000_36.49.12436.5","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(81)90225-X"},{"key":"2023041803223505000_36.49.12436.6","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12371"},{"key":"2023041803223505000_36.49.12436.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3520-07.2007"},{"key":"2023041803223505000_36.49.12436.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.016"},{"key":"2023041803223505000_36.49.12436.9","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91001-9"},{"key":"2023041803223505000_36.49.12436.10","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199809140-00016"},{"key":"2023041803223505000_36.49.12436.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-062111-150444"},{"key":"2023041803223505000_36.49.12436.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3241"},{"key":"2023041803223505000_36.49.12436.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2339-11.2011"},{"key":"2023041803223505000_36.49.12436.14","doi-asserted-by":"crossref","first-page":"9187","DOI":"10.1523\/JNEUROSCI.20-24-09187.2000","article-title":"Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system","volume":"20","author":"Cirelli","year":"2000","journal-title":"J Neurosci"},{"key":"2023041803223505000_36.49.12436.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0949-04.2004"},{"key":"2023041803223505000_36.49.12436.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5290.1211"},{"key":"2023041803223505000_36.49.12436.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00814-6"},{"key":"2023041803223505000_36.49.12436.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4845-04.2005"},{"key":"2023041803223505000_36.49.12436.19","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21274"},{"key":"2023041803223505000_36.49.12436.20","doi-asserted-by":"crossref","unstructured":"de Vivo L Bellesi M Marshall W Bushong EA Ellisman MH Tononi G Cirelli C (2016) Ultrastructural evidence for synaptic scaling across the wake\/sleep cycle. Science, In press.","DOI":"10.1126\/science.aah5982"},{"key":"2023041803223505000_36.49.12436.21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad4821"},{"key":"2023041803223505000_36.49.12436.22","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/sleep\/30.12.1617","article-title":"Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves","volume":"30","author":"Esser","year":"2007","journal-title":"Sleep"},{"key":"2023041803223505000_36.49.12436.23","doi-asserted-by":"publisher","DOI":"10.1038\/nn1568"},{"key":"2023041803223505000_36.49.12436.24","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(78)90266-3"},{"key":"2023041803223505000_36.49.12436.25","first-page":"155","article-title":"Genetic determinants of sleep regulation in inbred mice","volume":"22","author":"Franken","year":"1999","journal-title":"Sleep"},{"key":"2023041803223505000_36.49.12436.26","doi-asserted-by":"crossref","unstructured":"Grill WM (2008) in Indwelling neural implants: strategies for contending with the in vivo environment, Signal considerations for chronically implanted electrodes for brain interfacing, ed Reichert WM (CRC, Boca Raton, FL), pp 41\u201362.","DOI":"10.1201\/9781420009309.pt2"},{"key":"2023041803223505000_36.49.12436.27","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/sleep\/32.6.719","article-title":"Effects of skilled training on sleep slow wave activity and cortical gene expression in the rat","volume":"32","author":"Hanlon","year":"2009","journal-title":"Sleep"},{"key":"2023041803223505000_36.49.12436.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.11.024"},{"key":"2023041803223505000_36.49.12436.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)63818-2"},{"key":"2023041803223505000_36.49.12436.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02248-9"},{"key":"2023041803223505000_36.49.12436.31","doi-asserted-by":"publisher","DOI":"10.1038\/nature02663"},{"key":"2023041803223505000_36.49.12436.32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1636-08.2008"},{"key":"2023041803223505000_36.49.12436.33","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/sleep\/32.10.1273","article-title":"Sleep-dependent improvement in visuomotor learning: a causal role for slow waves","volume":"32","author":"Landsness","year":"2009","journal-title":"Sleep"},{"key":"2023041803223505000_36.49.12436.34","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90496-3"},{"key":"2023041803223505000_36.49.12436.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120997109"},{"key":"2023041803223505000_36.49.12436.36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.20.1.185"},{"key":"2023041803223505000_36.49.12436.37","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs389"},{"key":"2023041803223505000_36.49.12436.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01124-7"},{"key":"2023041803223505000_36.49.12436.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.03.070"},{"key":"2023041803223505000_36.49.12436.40","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1998.0051"},{"key":"2023041803223505000_36.49.12436.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.013"},{"key":"2023041803223505000_36.49.12436.42","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1152\/jn.2001.85.5.1969","article-title":"Natural waking and sleep states: a view from inside neocortical neurons","volume":"85","author":"Steriade","year":"2001","journal-title":"J Neurophysiol"},{"key":"2023041803223505000_36.49.12436.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2005.05.002"},{"key":"2023041803223505000_36.49.12436.44","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/415250"},{"key":"2023041803223505000_36.49.12436.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.12.025"},{"key":"2023041803223505000_36.49.12436.46","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3494"},{"key":"2023041803223505000_36.49.12436.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.024"},{"key":"2023041803223505000_36.49.12436.48","doi-asserted-by":"publisher","DOI":"10.1038\/nature10009"},{"key":"2023041803223505000_36.49.12436.49","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20814"},{"key":"2023041803223505000_36.49.12436.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.06.004"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1614-16.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T10:48:24Z","timestamp":1681814904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1614-16.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,7]]},"references-count":50,"journal-issue":{"issue":"49","published-online":{"date-parts":[[2016,12,7]]},"published-print":{"date-parts":[[2016,12,7]]}},"alternative-id":["10.1523\/JNEUROSCI.1614-16.2016"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1614-16.2016","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,7]]}}}