Circadian rhythms and memory formation

Key Points The regulation of memory formation by circadian rhythms and/or time-of-day effects is phylogenetically conserved in many species — including invertebrates and vertebrates — and correlates with cycling levels of melatonin. These features may be independent of changes in behavioural state (that is, wakefulness and sleep). The time-of-day-dependent regulation of neurophysiological parameters, such as spontaneous firing rate and resting membrane potential of neurons, are also phylogenetically conserved between invertebrate and vertebrate models. Circadian and time-of-day-dependent regulation of synaptic plasticity occurs in various mammalian models and can be considered a natural form of metaplasticity. Across phylogeny, similar molecular machinery underlies the processes of generating circadian rhythms and memory formation. These involve the expression of clock genes and the cyclic AMP–mitogen-activated protein kinase (MAPK)–cAMP-responsive element-binding protein (CREB) cascade. The maintenance of long-term memory seems to require oscillation of the cAMP–MAPK–CREB pathway. From these data, a model emerges suggesting that this maintenance of memory requires essentially autonomous molecular oscillators within memory-forming cells. Circadian cycling of biological processes is widely conserved across phylogeny. Gerstner and Yin discuss how regulators of circadian rhythms — including clock genes, melatonin and the suprachiasmatic nucleus — affect synaptic plasticity and memory formation. There has been considerable progress in elucidating the molecular mechanisms that contribute to memory formation and the generation of circadian rhythms. However, it is not well understood how these two processes interact to generate long-term memory. Recent studies in both vertebrate and invertebrate models have shown time-of-day effects on neurophysiology and memory formation, and have revealed a possible role for cycling molecules in memory persistence. Together, these studies suggest that common mechanisms underlie circadian rhythmicity and long-term memory formation.