Abstract

Early life programming has important consequences for future health and wellbeing. A key new aspect is the impact of perinatal light on the circadian system. Postnatal light environment will program circadian behavior, together with cell morphology and clock gene function within the suprachiasmatic nucleus (SCN) of the hypothalamus, the principal circadian clock in mammals. Nevertheless, it is still not clear whether the observed changes reflect a processing of an altered photic input from the retina, rather than an imprinting of the intrinsic molecular clock mechanisms. Here, we addressed the issue by systematically probing the mouse circadian system at various levels. Firstly, we used electroretinography, pupillometry and histology protocols to show that gross retinal function and morphology in the adult are largely independent of postnatal light experiences that modulate circadian photosensitivity. Secondly, we used circadian activity protocols to show that only the animal's behavioral responses to chronic light exposure, but not to constant darkness or the acute responses to a light stimulus depend on postnatal light experience. Thirdly, we used real-time PER2::LUC rhythm recording to show long-term changes in clock gene expression in the SCN, but also heart, lung and spleen. The data showed that perinatal light mainly targets the long-term adaptive responses of the circadian clock to environmental light, rather than the retina or intrinsic clock mechanisms. Finally, we found long-term effects on circadian peripheral clocks, suggesting far-reaching consequences for the animal's overall physiology.

Highlights

  • The suprachiasmatic nucleus (SCN) in the hypothalamus organizes physiology and behavior of an individual in a 24 h fashion, and synchronizes them to the particular environment the animal lives in

  • Effects of postnatal light environment on adult mouse retinal function and structure Light is key to synchronize the internal clock to the external environment [26]

  • It is detected by rod and cone photoreceptors in the retina, which convey image-forming visual information [27], along with the intrinsically photosensitive retinal ganglion cells, which express melanopsin and play an important role in circadian entrainment [28]

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Summary

Introduction

The suprachiasmatic nucleus (SCN) in the hypothalamus organizes physiology and behavior of an individual in a 24 h fashion, and synchronizes them to the particular environment the animal lives in. Several studies in the last few years have highlighted the fact that postnatal environment, and in particular light, exerts a major long-lasting influence on the individual’s circadian system later in life [2]. This may occur in preterm babies exposed to abnormal light environments in Neonatal Intensive Care Units, as this experience can affect their short-term recovery and growth [3], together with their long-term sleep patterns and neurodevelopment [4,5]. It is critical to determine the mechanisms behind early programming of the circadian system by light, as a first step towards uncovering the consequences of abnormal light exposure during development

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