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Melanopsin is a photopigment found in specialized ganglion cells of the retina that are involved in the regulation of circadian rhythms and pupillary reflex. In structure, melanopsin is an opsin, a variety of G-protein-coupled receptor. It is presumed that melanopsin signals through a G-protein of the Gq family, as invertebrate opsins are known to do, but this is not firmly established. It is also believed to be similar to invertebrate opsins in possessing an intrinsic photoisomerase activity.

The first electrophysiological light responses recorded from melanopsin ganglion cells were done in the lab of Dr. David Berson at Brown University. By using a combination of pharmacological agents to block synaptic communication in the retina, and isolating single melanopsin ganglion cells, his lab established melanopsin ganglion cells as being intrinsically photosensitive, and thus being a third class of mammalian photoreceptors. Further studies from his lab have concluded that melanopsin ganglion cells exhibit both light and dark adaptation, similar to classic rod and cone photoreceptors. Unlike rods and cones, however, melanopsin ganglion cells are responsible for non-image forming visual reflexes.

When light activates the melanopsin signaling system, the melanopsin-containing ganglion cells discharge nerve impulses, which are conducted through their axons in the optic nerve to specific brain targets. These targets include the suprachiasmatic nucleus of the hypothalamus (the master pacemaker of circadian rhythms) and the olivary pretectal nucleus (a center responsible for controlling the pupil of the eye). Melanopsin ganglion cells are thought to influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP).

Experiments have shown that light entrainment, by which periods of behavioral activity or inactivity (sleep) are synchronized with the light-dark cycle, is not as effective in melanopsin knockout mice, while rod and cone photoreceptor double knockouts still exhibit circadian entrainment and pupillary reflex.

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