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Spatial sensitivity of human circadian response: Melatonin suppression from on-axis and off-axis light exposures.

ABSTRACT: A better understanding of the spatial sensitivity of the human circadian system to photic stimulation can provide practical solutions for optimized circadian light exposures. Two psychophysical experiments, involving 25 adult participants in Experiment 1 (mean age = 34.0 years [SD 15.5]; 13 females) and 15 adult participants in Experiment 2 (mean age = 43.0 years [SD 12.6]; 12 females), were designed to investigate whether varying only the spatial distribution of luminous stimuli in the environment while maintaining a constant spectrally weighted irradiance at the eye could influence nocturnal melatonin suppression. Two spatial distributions were employed, one where the luminous stimulus was presented On-axis (along the line of sight) and one where two luminous stimuli were both presented Off-axis (laterally displaced at center by 14°). Two narrowband LED light sources, blue (λ_max = 451 nm) for first experiment and green (λ_max = 522 nm) for second experiment, were used in both the On-axis and the Off-axis spatial distributions. The blue luminous stimulus targeting the fovea and parafovea (On-axis) was about three times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis). The green luminous stimulus targeting the fovea and parafovea (On-axis) was about two times more effective for suppressing melatonin than the photometrically and spectrally matched stimulus targeting the more peripheral retina (Off-axis).

SUBMITTER: Nagare R

PROVIDER: S-EPMC8278206 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated.

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Spatial sensitivity of human circadian response: Melatonin suppression from on-axis and off-axis light exposures.

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