Modeling the circadian dynamics of morning and evening oscillators and the role of circadian rhythm in learning and memory

Abstract

Circadian rhythms (CR) are 24h endogenous oscillations seen in all organisms that control different biological processes including sleep-wake cycles, body temperature, cell division cycle, heartbeat, and metabolic rates. Light, the prime zeitgeber, accounts for the day-night changes and seasonal variation of the environment, and it modifies the endogenous (free running) period of the circadian rhythm, known as entrainment. In mammals, suprachiasmatic nucleus (SCN) is the main brain region that acts as a circadian master oscillator, which controls all the other peripheral oscillators. The circadian pacemaker in SCN plays an important role in encoding day length and seasonal changes. Identifying the molecular mechanism responsible for this encoding is an interesting problem that has attracted attention for a considerable period of time. A set of hypothesis has been proposed by Daan and his colleagues that the encoding is done by the circadian pacemaker that consists of two distinct oscillators of which one is the morning (M) oscillator that locks on to dawn and controls the morning activities, while the other is an evening (E) oscillator that locks on to the dusk and controls the evening activities. So far Daan’s hypotheses have neither been confirmed nor verified. The other problems that have attracted attention recently are the experimental generation of daily variation in firing patterns and the circadian modulation of synaptic plasticity, learning, and memory. However, molecular mechanisms responsible for the generation of daily varying firing patterns and the role of circadian rhythms in modulating learning and memory are not clearly delineated. Understanding of these problems requires careful construction of mathematical models with different time scales based on molecular mechanism of gene regulatory and signaling pathways.