Locus ceruleus control of slow-wave homeostasis.
Sleep intensity is regulated by the duration of previous wakefulness, suggesting that waking results in the progressive accumulation of sleep need (Borbely and Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which increases in proportion to the time spent awake. However, the mechanisms responsible for the increase of NREM SWA after wakefulness remain unclear. According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA occurs because during wakefulness, many cortical circuits undergo synaptic potentiation, as evidenced by the widespread induction of long-term potentiation (LTP)-related genes in the brain of awake animals. A direct prediction of this hypothesis is that manipulations interfering with the induction of LTP-related genes should result in a blunted SWA response. Here, we examined SWA response in rats in which cortical norepinephrine (NA) was depleted, a manipulation that greatly reduces the induction of LTP-related genes during wakefulness (Cirelli and Tononi, 2004). We found that the homeostatic response of the lower-range SWA was markedly and specifically reduced after NA depletion. These data suggest that the wake-dependent accumulation of sleep need is causally related to cellular changes dependent on NA release, such as the induction of LTP-related genes, and support the hypothesis that sleep SWA homeostasis may be related to synaptic potentiation during wakefulness.
Cirelli
Chiara
C
Department of Psychiatry, University of Wisconsin, Madison, Madison, Wisconsin 53719, USA. ccirelli@wisc.edu
Huber
Reto
R
Gopalakrishnan
Anupama
A
Southard
Teresa L
TL
Tononi
Giulio
G
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D004569:Electroencephalography / Q000379:methods; D005473:Fluoxetine / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology*; D012893:Sleep Wake Disorders / Q000503:physiopathology*; D013057:Spectrum Analysis / Q000379:methods; D013997:Time Factors; D014851:Wakefulness
D001596:Benzylamines; D004298:Dopamine; D005473:Fluoxetine; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C012102:DSP 4