Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA.
Curr Top Med Chem. 2011;11(19):2472-82. doi: 10.2174/156802611797470312.
Sleep is homeostatically regulated in all species that have been carefully studied. In mammals and birds, the best characterized marker of sleep pressure is slow wave activity (SWA), defined as the electroencephalogram (EEG) power between 0.5 and 4 Hz during NREM sleep. SWA peaks at sleep onset and decreases with time spent asleep, and reflects the synchronous firing of cortical neurons coordinated by an underlying slow oscillation, the fundamental cellular phenomenon of NREM sleep. We have recently proposed the synaptic homeostasis hypothesis of sleep, which claims that an important function of sleep is to maintain synaptic balance. This hypothesis states that plastic processes during wake are biased towards synaptic potentiation, resulting in a net increase in synaptic strength in many brain circuits. Such increased synaptic weight would be unsustainable in the long run, due to increased demand for energy, space and supplies, and risk of synaptic saturation. Thus, according to the synaptic homeostasis hypothesis, sleep is important to renormalize synaptic strength to a baseline level that is sustainable and beneficial for memory and performance. There is strong evidence that the amplitude and slope of EEG slow waves is related to the number of neurons that enter an up state or a down state of the slow oscillation near-synchronously, and that synchrony is directly related to the number, strength, and efficacy of synaptic connections among them. Thus, the average synaptic strength (number or efficacy of synapses) reached in a given cortical area at the end of the major wake phase should be reflected by the level of SWA in the EEG at sleep onset. Moreover, according to the hypothesis, sleep SWA is not only a useful proxy of wake-related cortical synaptic strength, but could mediate the renormalization of neural circuits by favoring net synaptic depression, perhaps aided by low levels of norepinephrine, serotonin, and acetylcholine during NREM sleep. Here we briefly review human and animal studies showing that, consistent with this hypothesis, 1) in the adult cerebral cortex wake is associated with a net increase in synaptic strength, and sleep with a net decrease; and 2) SWA reflects not just prior "use" of specific neuronal circuits, but rather the occurrence of plastic changes, with increases in SWA after synaptic potentiation, and decreases in SWA after synaptic depression. We end by discussing current challenges to this hypothesis and future research directions.
在所有经过精心研究的物种中，睡眠都受到稳态调节。在哺乳动物和鸟类中，睡眠压力的最佳特征标志物是慢波活动（SWA），定义为 NREM 睡眠期间 0.5 至 4 Hz 之间的脑电图（EEG）功率。SWA 在睡眠开始时达到峰值，并随睡眠时间的增加而减少，反映了皮质神经元在潜在慢波下的同步放电，这是 NREM 睡眠的基本细胞现象。我们最近提出了睡眠的突触稳态假说，该假说声称睡眠的一个重要功能是维持突触平衡。该假说指出，清醒时的可塑性过程偏向于突触增强，导致许多脑回路中的突触强度净增加。由于对能量、空间和供应的需求增加以及突触饱和的风险，这种增加的突触重量从长远来看是不可持续的。因此，根据突触稳态假说，睡眠对于将突触强度恢复到可持续且有益于记忆和表现的基线水平非常重要。有强有力的证据表明，EEG 慢波的幅度和斜率与同步进入慢波上下状态的神经元数量有关，而同步性与它们之间的突触连接数量、强度和功效直接相关。因此，在主要清醒阶段结束时，特定皮质区域中达到的平均突触强度（突触数量或功效）应反映在睡眠开始时 EEG 中的 SWA 水平。此外，根据该假说，睡眠 SWA 不仅是与清醒相关的皮质突触强度的有用替代物，而且可以通过有利于净突触抑制来调节神经回路的重新正常化，也许在 NREM 睡眠期间，去甲肾上腺素、血清素和乙酰胆碱的低水平可以辅助这种抑制。在这里，我们简要回顾了人类和动物研究，这些研究表明，与该假说一致，1）在成人大脑皮质中，清醒与突触强度的净增加有关，而睡眠则与突触强度的净减少有关；2）SWA 不仅反映了特定神经元回路的先前“使用”，而且反映了可塑性变化的发生，突触增强后 SWA 增加，突触抑制后 SWA 减少。最后，我们讨论了该假说的当前挑战和未来研究方向。
