Close up image of an eye.

Central Projections of Intrinsically Photosensitive Retinal Ganglion Cells in the Macaque Monkey

The hypothalamic suprachiasmatic nucleus (SCN) is the master clock responsible for controlling circadian rhythms in mammals1. These rhythmic cycles generated by the SCN are entrained to the environmental light/dark cycle via photic signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin. In addition to their critical role in nonimage-forming vision, ipRGCs also project to the lateral geniculate nucleus (LGN) to modulate conscious vision, and the pretectal olivary nucleus (PON) to control pupil constriction2, 3, 4. Orexin is a neuropeptide that regulates arousal, wakefulness, and appetite. Orexingeric cells in the posterior hypothalamus receive input from the circadian system5. It has been reported that orexin is present in melanopsin-expressing ipRGCs6, 7. However, most knowledge of these cells has been gained from studies on nocturnal rodents, whose visual systems are distantly related to those of humans and other diurnal primates. Injection of cholera toxin B (CtB), an anterograde axonal tracer, was used to visualize retinal projections in the brain, and anti-orexin antibodies were used to determine if these projections also contained orexin.

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