Abstract
Purpose: :
It is well established that the retina contains intrinsically photosensitive ganglion cells (ipRGCs), which express melanopsin as their photopigment and serve non-image forming visual functions. Indirect evidence suggests there may be multiple types of ipRGCs in rodents, and a recent report in the primate introduced a novel, inner-stratifying type with a possible role in form vision. Here we identify a similar ipRGC, previously unknown in the rodent retina.
Methods: :
Ganglion cells with somata much larger than those of known rodent ipRGCs were targeted for whole-cell patch-clamp recordings in unlabelled mouse retinae. Their responses to bright light stimuli were tested in Ames medium and under synaptic blockade by drugs. The cells were filled with Lucifer Yellow and Neurobiotin and the retinae immunostained for melanopsin.
Results: :
We did indeed encounter a large ganglion cell type that continued to respond to light in the presence of blockers of major retinal transmitter receptors (n = 13 of 55). The intrinsic photosensitivity of these cells persisted when Co2+ blocked synaptic release (n = 2) and in connexin-36 knock-out mice, which lack most retinal gap junctions (n = 5). The newly identified cells differ markedly in morphology from previously reported rodent ipRGCs, which innervate the suprachiasmatic nucleus (SCN). They have very large somata and large alpha-like dendritic arbors that stratify in the ON sublamina of the inner plexiform layer. These cells receive ON rod/cone inputs and show weaker intrinsic light responses than the original ipRGCs. The sluggish kinetics and short-wavelength preference of their intrinsic responses point to melanopsin-based phototransduction. However, we couldn’t detect melanopsin immunofluorescence in these cells. We suspect this is due to low expression levels, because a sensitive immunoperoxidase method did reveal faint profiles of large cells in the ganglion cell layer.
Conclusions: :
We have found a new ipRGC type in the mouse retina. These cells have ON morphology and physiology. Their intrinsic light responses are probably melanopsin based, but they do not project to the SCN. Our findings are in agreement with parallel observations in a mouse line expressing fluorescent proteins in melanopsin ganglion cells (see abstract by Wong et al.).
Keywords: ganglion cells • photoreceptors • electrophysiology: non-clinical