Abstract
Abstract
Intrinsically light sensitive retinal ganglion cells through melanopsin photoreception (mRGCs) are important for fundamental regulatory brain processes such as circadian rhythms, mood, acute sleep, and pupillary constriction. While previous research in animal models indicates temporal differences in maturation of mRGC mediated projections, corresponding developmental patterns have not been studied in human infants. To elucidate the roles of mRGCs in early development of regulation of pupillary constriction and sleep/wake patterns, we here explore the maturation of mRGC mediated photoentrainment in human infants aged 1 to 12 months, using non-invasive eye tracking pupillometry and sleep diaries. Although the mRGCs relay rod/cone activation in a range of light intensities, it is possible to separate rod/cone/mRGC activation due to the photoreceptors’ color sensitivity and temporal responsiveness. We therefore used sustained red and blue light stimulation after partial dark adaptation to characterize developmental changes in wavelength-dependent mRGC-relayed pupillary responses. Infants’ pupil responses indicate a prolonged post-natal mRGC maturation to the shell of the olivary pretectal nucleus during the first year. This response was separate from infants’ sleep/wake patterns, which parallels findings from cellular research on murines: the mRGCs have separate pathways for photoentrainment of pupillary constriction and sleep/wake patterns, which develop with different temporal dynamics. Together, these findings provide the first characterization of developmental changes in mRGC-relayed pupillary responses in human infants, and an initial step towards bridging human mRGC network development with murine and human adult mRGC research.
Statement of significance
The retina contains rods, cones, and a more recently discovered photoreceptor called intrinsically photosensitive retinal ganglion cells (mRGC). One subtype of mRGCs project to the brain’s main area for circadian rhythms, the suprachiasmatic nucleus, and control photoentrainment of circadian rhythms such as day/night sleep patterns. While mRGCs have been extensively studied in murines and with adults there are no previous studies on typically developing infants. We here fill this gap and examine infant mRGC mediated activation using pupillary responses to red and blue light in relation to sleep/wake behavior, at an age range where light entrained sleep patterns emerge. The results parallels findings in animal research, and thereby start bridging literatures in animal research, adult sleep, and infant sleep.