Coexistence within one cell of microvillous and ciliary phototransductions across M1- through M6-IpRGCs

Significance

Intrinsically photosensitive retinal ganglion cells (ipRGCs) were discovered relatively recently. They mediate non-image and partly image vision and are currently divided into six subtypes (M1 through M6) based on their dendritic morphology and arborization locations. Previously, we found that M1-, M2-, and M4-ipRGCs have two co-existent phototransduction mechanisms within a given cell, one involving phospholipase C beta 4 (PLCβ4) and canonical transient receptor potential 6 and 7 (TRPC6,7) channels (microvillous motif) and the other involving cyclic Adenosine Monophosphate (cAMP) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ciliary motif). We now found the same in M3-, M5-, and M6-ipRGCs, although different percentage representations by the two mechanisms are present broadly across the six subtypes for bright-flash responses.

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as primary photoceptors by expressing the photopigment, melanopsin, and also as retinal relay neurons for rod and cone signals en route to the brain, in both cases for the purpose of non-image vision as well as aspects of image vision. So far, six subtypes of ipRGCs (M1 through M6) have been characterized. Regarding their phototransduction mechanisms, we have previously found that, unconventionally, rhabdomeric (microvillous) and ciliary signaling motifs co-exist within a given M1-, M2-, and M4-ipRGC, with the first mechanism involving PLCβ4 and TRPC6,7 channels and the second involving cAMP and HCN channels. We have now examined M3-, M5-, and M6-cells and found that each cell likewise uses both signaling pathways for phototransduction, despite differences in the percentage representation by each pathway in a given ipRGC subtype for bright-flash responses (and saturated except for M6-cells). Generally, M3- and M5-cells show responses quite similar in kinetics to M2-responses, and M6-cell responses resemble broadly those of M1-cells although much lower in absolute sensitivity and amplitude. Therefore, similar to rod and cone subtypes in image vision, ipRGC subtypes possess the same phototransduction mechanism(s) even though they do not show microvilli or cilia morphologically.