title: Why Does Sleep Slow-Wave Activity Increase After Extended Wake? Assessing the Effects of Increased Cortical Firing During Wake and Sleep.
abstract: 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 "fatigue": 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.
  
  
  
  A long-standing hypothesis is that neurons fire less during slow-wave sleep to recover from the "fatigue" 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.
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719.|Neuroscience Training Program and.
authors.forename: Alexander V
authors.identifier: 0000-0002-0547-8842
authors.initials: AV
authors.lastname: Rodriguez
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719.|Neuroscience Training Program and.|Medical Scientist Training Program, University of Wisconsin Health Sciences Learning Center, Madison, Wisconsin 53705.
authors.forename: Chadd M
authors.identifier: 0000-0001-6399-7803
authors.initials: CM
authors.lastname: Funk
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and.
authors.forename: Vladyslav V
authors.identifier: 0000-0002-4336-6681
authors.initials: VV
authors.lastname: Vyazovskiy
authors.affiliation: Sagol School of Neurosciences and.|Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yuval
authors.identifier: 0000-0002-5433-6349
authors.initials: Y
authors.lastname: Nir
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719, ccirelli@wisc.edu.
authors.forename: Chiara
authors.identifier: 0000-0003-2563-677X
authors.initials: C
authors.lastname: Cirelli
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000502:physiology; D007834:Lasers; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D062308:Optogenetics; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation; D014851:Wakefulness / Q000502:physiology*
keywords: NREM sleep; cerebral cortex; fatigue; mouse; optogenetics; sleep deprivation