Melanopsin Signalling: Low Pigment Density, Large Single-Photon Response, And High-Efficiency Transmission

A subset of retinal ganglion cells has recently been discovered to be intrinsically photosensitive. These cells use melanopsin as the visual pigment and are the only photoreceptors known in mammals besides rods and cones. They project primarily to brain centers that serve non-image-forming visual functions such as the pupillary light reflex and circadian photoentrainment. How well these cells signal intrinsic light absorption to drive such behaviors remains unclear. We have used perforated-patch and loose-patch recordings to study mouse ipRGCs that are genetically labeled by a fluorescent protein, tdTomato. Here we report fundamental parameters that govern their intrinsic light responses, and the associated spike generation. They express melanopsin at a membrane density that is four orders of magnitude lower than that of rod and cone pigments (∼3 μm2), giving rise to a low photon-catch and thus a phototransducing role in relatively bright light. Nonetheless, the single-photon response is even larger than that of rods, suggesting high amplification in melanopsin phototransduction. It is also extraordinarily prolonged, with an integration time that is ∼20-fold longer than that of rods, and has a unique shape among known photoreceptors. Remarkably, ipRGCs are capable of signalling single-photon absorption to the brain. Moreover, a flash resulting in a few hundred isomerized melanopsin molecules in a retina is sufficient for reaching the threshold of the pupillary light reflex.