Functional Interactions Between Sleep and Circadian Rhythms in Learning and Learning Disabilities

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_A 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.