Abstract
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous organization of the SCN is presented and used to study the implication of the SCN network topology on synchronization and entrainment properties. The results show that oscillations with larger amplitude can be obtained with scale-free networks, in contrast to random and local connections. Networks with the small-world property such as the scale-free networks used in this work can adapt faster to a delay or advance in the light/dark cycle (jet lag). Interestingly a certain level of cellular heterogeneity is not detrimental to synchronization performances, but on the contrary helps resynchronization after jet lag. When coupling two networks with different topologies that mimic the two regions of the SCN, efficient filtering of pulse-like perturbations in the entrainment pattern is observed. These results suggest that the complex and heterogeneous architecture of the SCN decreases the sensitivity of the network to short entrainment perturbations while, at the same time, improving its adaptation abilities to long term changes.
Highlights
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker [1,2]
The circadian pacemaker is composed of about 20,000 neurons, called the suprachiasmatic nucleus (SCN) located in the hypothalamus
The SCN receives light signals from the retina and controls peripheral circadian clocks to ensure the proper timing of physiological processes
Summary
The suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker [1,2]. The SCN comprises about 20000 densely packed neurons organized into bilateral pairs of nuclei on each side of the third ventricle, above the optic chiasm [2] (Fig. 1). The SCN controls circadian rhythms in other parts of the brain including the cortex and the pineal gland, as well as in peripheral tissues such as the liver, kidney, and heart. This hierarchical organization of the circadian system ensures the proper timing of physiological processes and behavior [1,3]. In response and anticipation to this cycling environment, the circadian pacemaker adjusts the phase of clock-controlled processes with respect to the light-dark cycle
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