A Broad Role for Melanopsin in Nonvisual Photoreception

Aug 9, 2003The Journal of neuroscience : the official journal of the Society for Neuroscience

A wide role for melanopsin in light detection beyond vision

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Abstract

Melanopsin is expressed in two-thirds of retinal ganglion cells (RGCs) projecting to the suprachiasmatic nucleus (SCN) and contralateral pretectal area (PTA).

Rod and cone photoreceptors are not necessary for light-induced circadian entrainment or other nonvisual photoreceptive responses.
Melanopsin is found in a majority of RGCs that project to the SCN, ventral subparaventricular zone (vSPZ), and ventrolateral preoptic nucleus (VLPO).
A significant portion of RGCs that express melanopsin mRNA also innervate the PTA and intergeniculate leaflet (IGL), but not the dorsal lateral geniculate nucleus or superior colliculus.
Approximately one-fifth of RGCs project to the ipsilateral IGL while two-thirds project to both the SCN and contralateral PTA.
Double-retrograde tracing indicates that a specific subgroup of RGCs projects to both the SCN and PTA, with most containing melanopsin mRNA.

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The rod and cone photoreceptors that mediate visual phototransduction in mammals are not required for light-induced circadian entrainment, negative masking of locomotor activity, suppression of pineal melatonin, or the pupillary light reflex. The photopigment melanopsin has recently been identified in intrinsically photosensitive retinal ganglion cells (RGCs) that project to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus, suggesting that melanopsin might influence a variety of irradiance-driven responses. We have found novel projections from RGCs that express melanopsin mRNA to the ventral subparaventricular zone (vSPZ), a region involved in circadian regulation and negative masking, and the sleep-active ventrolateral preoptic nucleus (VLPO) and determined the subsets of melanopsin-expressing RGCs that project to the SCN, the pretectal area (PTA), and the IGL division of the lateral geniculate nucleus (LGN). Melanopsin was expressed in the majority of RGCs that project to the SCN, vSPZ, and VLPO and in a subpopulation of RGCs that innervate the PTA and the IGL but not in RGCs projecting to the dorsal LGN or superior colliculus. Two-thirds of RGCs containing melanopsin transcript projected to each of the SCN and contralateral PTA, and one-fifth projected to the ipsilateral IGL. Double-retrograde tracing from the SCN and PTA demonstrated a subpopulation of RGCs projecting to both sites, most of which contained melanopsin mRNA. Our results suggest that melanopsin expression defines a subset of RGCs that play a broad role in the regulation of nonvisual photoreception, providing collateralized projections that contribute to circadian entrainment, negative masking, the regulation of sleep-wake states, and the pupillary light reflex.

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A Broad Role for Melanopsin in Nonvisual Photoreception

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