Programming of mice circadian photic responses by postnatal light environment.

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.

Development of circadian rhythms: role of postnatal light environment.

Mammals are born with an immature circadian system, which completes its development postnatally. Evidence suggests that the environment experienced by a newborn will impact and shape its development, which will have future consequences at the levels of circadian system function, circadian behaviour and physiology, and potentially, the animal's long-term health and welfare. Here we review the various stages in postnatal development of the circadian system, and discuss the data available on the long-term effects of early environment, in particular light environment, on the animal's brain, physiology and behaviour.

Differential hypothalamic tyrosine hydroxylase distribution and activation by light in adult mice reared under different light conditions during the suckling period.

In mammals, early light experience during a critical period within the first 3 weeks of postnatal development has long-lasting effects on circadian locomotor activity behaviour and neuropeptide expression in the suprachiasmatic nucleus (SCN) of the hypothalamus, site of the principal pacemaker. Dopamine is thought to be involved in the modulation of photic input within the SCN and in tadpoles, the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of dopamine, in the SCN is altered by previous light history. We thus hypothesised that dopaminergic neurons may be important for the development of the adapted responses to light that we have previously observed. To test this, we raised mice in either constant darkness, 12:12 h light-dark cycles or constant light during the first 3 weeks after birth, and later examined the expression of TH and FOS in the hypothalamus of these mice as adults, both in the dark and after exposure to a light pulse. We found that early light experience affects TH and FOS expression, both baseline levels and in response to a light pulse, in brain areas which are directly connected to the SCN, and are associated with the circadian control of neuroendocrine function. Therefore, our results suggest that the long-lasting alterations induced by early light environment on several hypothalamic nuclei may be relayed through the SCN, and that TH-expressing cells may play a role in conveying/establishing these alterations. These data suggest a role of early light experience in the regulation of future hormonal homeostasis and circadian behaviour.