Reduced plasticity in coupling strength in the SCN clock in aging as revealed by Kuramoto modelling

The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consist of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is plastic and driven by the length of the day. With aging the capacity to behaviorally adapt to changes in the light regime reduces. The mechanisms underlying photoperiodic adaptation are largely unknown, but are important to unravel for the development of novel interventions to improve the quality of life of the elderly. We analyzed the neuronal synchronization of PER2::LUC protein expression in the SCN of young and old mice entrained to either long or short photoperiod and used the synchronization levels as input for a two-community noisy Kuramoto model. With the Kuramoto model we estimated the coupling strength between and within neuronal subpopulations. The model revealed that the coupling strength between and within subpopulations contributes to photoperiod induced changes in the phase relationship among neurons. We found that the SCN of young mice adapts in coupling strength over a large range, with low coupling strength in long photoperiod and higher coupling strength in short photoperiod. In aged mice we also found low coupling strength in long photoperiod, but strongly reduced capacity to reach high coupling strength in short photoperiod. The inability to respond with an increase in coupling strength shows that manipulation of photoperiod is not a suitable strategy to enhance clock function with aging. We conclude that the inability of aged mice to reach high coupling strength makes aged mice less capable to seasonal adaptation than young mice. Author SummaryCircadian clocks drive daily rhythms in physiology and behavior. In mammals the clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consist of a network of coupled neurons which are synchronized to produce a coherent rhythm. Due to plasticity of the network, seasonal adaptation to short winter days and long summer days occurs. Disturbances in circadian rhythmicity of the elderly have negative health effects, such as neurodegenerative diseases. With the rise in life expectancy this is becoming a major issue. In our paper, we used a model to compare the neuronal coupling in the SCN between young and old animals. We investigated whether exposure to short photoperiod can strengthen coupling among clock cells, and thereby clock function, in old animals. We observed that this is not possible, indicating that simple environmental manipulations are not an option. We suggest that receptor targeted interventions are required, setting the path for further investigation.