Abstract
BackgroundIntrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30.ResultsMelanopsin-positive cell density decreases by 17 % between post-natal days 8 and 15 and by 25 % between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes – Types I-III – have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology.ConclusionsType I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose melanopsin expression in development. These cells constitute a unique morphologic and physiologic class of ipRGCs functioning early in postnatal development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-015-0042-x) contains supplementary material, which is available to authorized users.
Highlights
Photosensitive retinal ganglion cells mediate circadian light entrainment and the pupillary light response in adult mice
The density of total melanopsin-positive cells decreased by 17 % between post-natal day 8 (P8) and P15, 10 % between P15 and P30, and 25 % between P8 and P30 (173 mm−2 to 129 mm−2, p = 0.001) (Table 1, Fig. 1b)
These densities are consistent with other recent intrinsically photosensitive retinal ganglion cells (ipRGC) surveys [16, 17]
Summary
Photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. Changes in ipRGC photosensitivity between early post-natal and adult ages have been reported in rd1/rd mice [5] and in transgenic mice expressing eGFP under the melanopsin promoter [13] These differences have not been systematically studied in large numbers of cells from wild-type mice. We study wild-type ipRGC light responses over the course of post-natal development using multi-electrode array recording, and find a general reduction in photosensitivity with increasing age. This reduction in light sensitivity is largely restricted to one electrophysiologic subtype of ipRGC (the Type I cell). Mice possess a specific population of ipRGCs with heightened intrinsic photosensitivity in early development that is largely lost in adulthood
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