Melanopsin ganglion cells extend dendrites into the outer retina during early postnatal development

Abstract

Melanopsin ganglion cells express the photopigment melanopsin and are the first functional photoreceptors to develop in the mammalian retina. They have been shown to play a variety of important roles in visual development and behavior in the early postnatal period (Johnson et al., 2010; Kirkby and Feller, 2013; Rao et al., 2013; Renna et al., 2011). Here, we probed the maturation of the dendritic arbors of melanopsin ganglion cells during this developmental period in mice. We found that some melanopsin ganglion cells (mainly the M1-subtype) transiently extend their dendrites not only into the inner plexiform layer (where they receive synaptic inputs from bipolar and amacrine cells) but also into the outer plexiform layer, where in mature retina, rod and cone photoreceptors are thought to contact only bipolar and horizontal cells. Thus, some immature melanopsin ganglion cells are biplexiform. This feature is much less common though still present in the mature retina. It reaches peak incidence 8–12 days after birth, before the eyes open and bipolar cells are sufficiently mature to link rods and cones to ganglion cells. At this age, some outer dendrites of melanopsin ganglion cells lie in close apposition to the axon terminals of cone photoreceptors and express a postsynaptic marker of glutamatergic transmission, postsynaptic density-95 protein (PSD-95). These findings raise the possibility of direct, monosynaptic connections between cones and melanopsin ganglion cells in the early postnatal retina. We provide a detailed description of the developmental profile of these processes and consider their possible functional and evolutionary significance.

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

“…As ipRGCs send ORDs to the outer retina during the first 2 post-natal weeks of life (Renna et al, 2015; Sondereker et al, 2017), we hypothesized that ipRGCs may be involved in organizing aspects of retinal architecture.…”

“…The recently discovered intrinsically photosensitive RGCs (ipRGCs), which also localize in the GCL, express the photo-pigment melanopsin and regulate photoentrainment and the pupillary light reflex (Güler et al, 2008€ ). Interestingly, ipRGCs have been recently described to send elaborate dendritic projections to the outer retina, which have been termed outer retinal dendrites (ORDs) (Renna et al, 2015; Sondereker et al, 2017). …”

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

“…This negative phototaxis behavior is mediated by melanopsin ganglion cells activity (4). Around this same developmental window of time, a small population of melanopsin ganglion cells extend dendrites through the inner retina into the OPL as early as P4 (8, 9). These Outer Retinal Dendrites (ORDs) are asymmetrically distributed to the dorsal retina, where cones predominately express m-opsin (9).…”

“…These Outer Retinal Dendrites (ORDs) are asymmetrically distributed to the dorsal retina, where cones predominately express m-opsin (9). ORDs are in close apposition to cone photoreceptor terminals and immuno-positive puncta labeling for post-synaptic density marker 95, an indicator of glutamatergic signaling, have been found (8). Taken together, early outer retinal photoreceptors currents have the potential to signal pre-synaptic partners as early as P8, five days earlier than previously thought.…”

“…Recent studies from our group have found anatomical evidence for a direct circuit from cones to a small population of M1-type melanopsin ganglion cells in the dorsal retina between P8 and P12 (8, 9). These studies suggest cones may be able bypass bipolar cells and signal ganglion cells directly, should these cones have the capacity to respond to light in this developmental window of time.…”