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

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Sleep-Wake Neurobiology and Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 253))

Abstract

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 GABAA 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.

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Acknowledgments

We are grateful to many colleagues who contributed to studies from our own laboratory that constitute the body of this chapter. In particular, they include Damien Colas, Craig Garner, Fabian Fernandez, Bayarsaikhan Chuluun, Asya Rolls, Megha Makam, and many Stanford University undergraduates. This work was supported by LumindRDS Foundation and NIMH MH095837.

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  1. Biology Department, Stanford University, Stanford, CA, USA

    H. Craig Heller & Norman F. Ruby

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  1. H. Craig Heller
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  2. Norman F. Ruby
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Correspondence to H. Craig Heller .

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Editors and Affiliations

  1. Human Sleep Psychopharmacology Laboratory, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland

    Hans-Peter Landolt

  2. Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

    Derk-Jan Dijk

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Heller, H.C., Ruby, N.F. (2018). Functional Interactions Between Sleep and Circadian Rhythms in Learning and Learning Disabilities. In: Landolt, HP., Dijk, DJ. (eds) Sleep-Wake Neurobiology and Pharmacology . Handbook of Experimental Pharmacology, vol 253. Springer, Cham. https://doi.org/10.1007/164_2018_176

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