A clock in mouse cones contributes to the retinal oscillator network and to synchronization of the circadian system

Multiple circadian clocks dynamically regulate mammalian physiology. In retina, rhythmic gene expression serves to align vision and tissue homeostasis with daily light changes. Photic input is relayed to the suprachiasmatic nucleus to entrain the master clock, which matches behaviour to environmental changes. Circadian organization of the mouse retina involves coordinated, layer-specific oscillators, but so far little is known about the cone photoreceptor clock and its role in the circadian system. Using the cone-only Nrl-/- mouse model we show that cones contain a functional self-sustained molecular clockwork. By bioluminescence-combined imaging we also show that cones provide substantial input to the retinal clock network. Furthermore, we found that light entrainment and negative masking in cone-only mice are subtly altered and that constant light displayed profound effects on their central clock. Thus, our study demonstrates the contribution of cones to retinal circadian organisation and their role in finely tuning behaviour to environmental conditions.

A Chimera Oscillatory State in a Globally Delay-Coupled Oscillator Network

Oscillatory behavior is absolutely necessary for the normal functioning of various organisms and their performance. Therefore, it is necessary to protect the oscillatory behavior in an aging network which consists of oscillatory and nonoscillatory nodes. In this work, we investigate numerically and theoretically the effect of time delay on oscillatory behaviors in a network which includes active and inactive Stuart–Landau oscillators. Interestingly, we find a chimera oscillatory state where a part of oscillators is a steady state while other oscillators preserve oscillatory motion; such dynamical behaviors are considered generally to be impossible for globally coupled systems when the coupling strength is sufficiently large. Furthermore, our results reveal that time delay can effectively inhibit aging transition and recover the oscillatory behavior from the aging network.

A myogenic motor pattern in mice lacking myenteric interstitial cells of Cajal explained by a second coupled oscillator network

The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are a network of coupled oscillators in the small intestine that generate rhythmic electrical phase waves leading to corresponding waves of contraction, yet rhythmic action potentials and intercellular calcium waves have been recorded from c-kit-mutant mice that lack the ICC-MP, suggesting that there may be a second pacemaker network. The gap junction blocker carbenoxolone induced a “pinstripe” motor pattern consisting of rhythmic “stripes” of contraction that appeared simultaneously across the intestine with a period of ~4 s. The infinite velocity of these stripes suggested they were generated by a coupled oscillator network, which we call X. In c-kit mutants rhythmic contraction waves with the period of X traveled the length of the intestine, before the induction of the pinstripe pattern by carbenoxolone. Thus X is not the ICC-MP and appears to operate under physiological conditions, a fact that could explain the viability of these mice. Individual stripes consisted of a complex pattern of bands of contraction and distension, and between stripes there could be slide waves and v waves of contraction. We hypothesized that these phenomena result from an interaction between X and the circular muscle that acts as a damped oscillator. A mathematical model of two chains of coupled Fitzhugh–Nagumo systems, representing X and circular muscle, supported this hypothesis. The presence of a second coupled oscillator network in the small intestine underlines the complexity of motor pattern generation in the gut. NEW & NOTEWORTHY Physiological experiments and a mathematical model indicate a coupled oscillator network in the small intestine in addition to the c-kit-expressing myenteric interstitial cells of Cajal. This network interacts with the circular muscle, which itself acts as a system of damped oscillators, to generate physiological contraction waves in c-kit (W) mutant mice.