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K. Y. Wong, J. L. Ecker, O. N. Dumitrescu, D. M. Berson, S. Hattar; Multiple Morphological Types of Melanopsin Ganglion Cells with Distinct Light Responses and Axonal Targets. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1518. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically photosensitive retinal ganglion cells (ipRGCs) use the photopigment melanopsin and drive non-image-forming visual behaviors such as circadian photoentrainment and the pupil reflex. There is increasing evidence in the literature that the ipRGCs we originally described (Berson et al., Science 2002; Hattar et al., Science 2002) represent just one subtype of melanopsin-containing RGCs. We wanted to identify the remaining types and characterize their light responses and potential functions.
Using the Cre-lox system in mice, all melanopsin-containing RGCs were made to express either alkaline phosphatase (to visualize their form and projections), or EGFP (to target them for whole-cell recording and dye-filling). Melanopsin-based photoresponses were recorded under synaptic blockade in heterozygotes.
Three morphological types of melanopsin-expressing RGC photoreceptors were identified. "M1" cells correspond to the established ipRGC type, with relatively small somas and sparse, disordered dendritic arbors in the OFF sublamina of the inner plexiform layer (IPL). M1s generate the fastest and largest intrinsic photoresponses. Two novel types were found. "M2" cells have medium-sized somas. Their dendritic arbors are more highly branched than those of M1 cells and they stratify in the ON sublamina. M2 cells generate slower and smaller intrinsic light responses than M1s. "M3" cells resemble ON alpha cells, with very large somas, and large radiate arbors of thick dendrites stratifying in the inner IPL. M3 cells generate the slowest and weakest photoresponses (see also abstract by Dumitrescu and Berson). M2 and/or M3 cells apparently share several central targets with M1 cells (suprachiasmatic nucleus [SCN], intergeniculate leaflet, ventral lateral geniculate nucleus [vLGN]), but terminate in different subregions of the olivary pretectal nucleus and superior colliculus, have stronger input to the dorsal LGN, and project less heavily if at all to the SCN and habenular region.
There are at least three distinct types of melanopsin-expressing ipRGCs in mice. These data may explain earlier reports of ipRGC response diversity in mice (Sekaran et al., Curr Biol 2003; Tu et al., Neuron 2005). Differences in axonal targets suggest that each type may serve a unique set of non-image-forming visual functions, and that some types may contribute to form vision as previously reported for primate ipRGCs (Dacey et al., Nature 2005).
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