Heller H Craig, Ruby Norman F
Biology Department, Stanford University, Stanford, CA, USA.
Handb Exp Pharmacol. 2019;253:425-440. doi: 10.1007/164_2018_176.
The propensity for sleep is timed by the circadian system. Many studies have shown that learning and memory performance is affected by circadian phase. And, of course it is well established that critical processes of memory consolidation occur during and depend on sleep. This chapter presents evidence that sleep and circadian rhythms do not just have separate influences on learning and memory that happen to coincide because of the circadian timing of sleep, but rather sleep and circadian systems have a critical functional interaction in the processes of memory consolidation. The evidence comes primarily from research on two models of learning disability: Down's syndrome model mice and Siberian hamsters. The Down's syndrome model mouse (Ts65Dn) has severe learning disability that has been shown to be due to GABAergic over-inhibition. Short-term, chronic therapies with GABA antagonists restore learning ability in these mice long-term, but only if the antagonist treatments are given during the dark or sleep phase of the daily rhythm. The Siberian hamster is a model circadian animal except for the fact that a light treatment that gives the animal a phase advance on one day and a phase delay on the next day can result in total circadian arrhythmia for life. Once arrhythmic, the hamsters cannot learn. Learning, but not rhythmicity, is restored by short-term chronic treatment with GABA antagonists. Like many other species, if these hamsters are made arrhythmic by SCN lesion, their learning is unaffected. However, if made arrhythmic and learning disabled by the light treatment, subsequent lesions of their SCNs restore learning. SCN lesions also appear to restore learning in the Ts65Dn mice. The collective work on these two animal models of learning disability suggests that the circadian system modulates neuroplasticity. Our hypothesis is that a previously unrecognized function of the circadian system is to dampen neuroplasticity during the sleep phase to stabilize memory transcripts during their transfer to long-term memory. Thus, sleep and circadian systems have integrated roles to play in memory consolidation and do not just have separate but coincident influences on that process.
睡眠倾向由昼夜节律系统定时。许多研究表明，学习和记忆表现受昼夜节律阶段的影响。当然，记忆巩固的关键过程在睡眠期间发生且依赖于睡眠，这一点已得到充分证实。本章提供的证据表明，睡眠和昼夜节律不仅仅是由于睡眠的昼夜定时而对学习和记忆产生单独影响，而且睡眠和昼夜节律系统在记忆巩固过程中具有关键的功能相互作用。证据主要来自对两种学习障碍模型的研究：唐氏综合征模型小鼠和西伯利亚仓鼠。唐氏综合征模型小鼠（Ts65Dn）存在严重的学习障碍，已证明这是由于GABA能过度抑制所致。用GABA拮抗剂进行短期慢性治疗可长期恢复这些小鼠的学习能力，但前提是拮抗剂治疗要在每日节律的黑暗或睡眠阶段进行。西伯利亚仓鼠是一种典型的昼夜节律动物，但有一种光照处理方式，即让动物在一天中提前一个阶段，在第二天延迟一个阶段，这可能导致其终生完全昼夜节律紊乱。一旦出现节律紊乱，仓鼠就无法学习。用GABA拮抗剂进行短期慢性治疗可恢复学习能力，但不能恢复节律性。与许多其他物种一样，如果通过损毁视交叉上核（SCN）使这些仓鼠出现节律紊乱，它们的学习不受影响。然而，如果通过光照处理使其出现节律紊乱并导致学习障碍，随后损毁它们的SCN可恢复学习能力。损毁SCN似乎也能恢复Ts65Dn小鼠的学习能力。对这两种学习障碍动物模型的综合研究表明，昼夜节律系统调节神经可塑性。我们的假设是，昼夜节律系统以前未被认识的功能是在睡眠阶段抑制神经可塑性，以便在记忆转录本向长期记忆转移过程中使其稳定。因此，睡眠和昼夜节律系统在记忆巩固中发挥着整合作用，而不仅仅是对该过程产生单独但同时发生的影响。
