Intrinsic Photosensitive Retinal Ganglion Cells in the Diurnal Rodent, Arvicanthis ansorgei

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a new class of photoreceptors which support a variety of non-image forming physiological functions, such as circadian photoentrainment, pupillary light reflex and masking responses to light. In view of the recently proposed role of retinal inputs for the regulation of diurnal and nocturnal behavior, we performed the first deep analysis of the ipRGC system in a diurnal rodent model, Arvicanthis ansorgei , and compared the anatomical and physiological properties of ipRGCs with those of nocturnal mice. Based on somata location, stratification pattern and melanopsin expression, we identified two main ipRGC types in the retina of Arvicanthis : M1, constituting 74% of all ipRGCs and non-M1 (consisting mainly of the M2 type) constituting the following 25%. The displaced ipRGCs were rarely encountered. Phenotypical staining patterns of ganglion cell markers showed a preferential expression of Brn3 and neurofilaments in non-M1 ipRGCs. In general, the anatomical properties and molecular phenotyping of ipRGCs in Arvicanthis resemble ipRGCs of the mouse retina, however the percentage of M1 cells is considerably higher in the diurnal animal. Multi-electrode array recordings (MEA) identified in newborn retinas of Arvicanthis three response types of ipRGCs (type I, II and III) which are distinguished by their light sensitivity, response strength, latency and duration. Type I ipRGCs exhibited a high sensitivity to short light flashes and showed, contrary to mouse type I ipRGCs, robust light responses to 10 ms flashes. The morphological, molecular and physiological analysis reveals very few differences between mouse and Arvicanthis ipRGCs. These data imply that the influence of retinal inputs in defining the temporal niche could be related to a stronger cone input into ipRGCs in the cone-rich Arvicanthis retina, and to the higher sensitivity of type I ipRGCs and elevated proportion of M1 cells.

Central melanopsin projections in the diurnal rodent, Arvicanthis niloticus

“…ipRGCs have not yet been described in the Nile grass rat but they have in a related day-active species, the Sudanese grass rat ( A. ansorgei ). Although several characteristics of these cells are similar to those reported in nocturnal rodents, some differences exist in the firing patterns of a select subtype of ipRGCs ( Karnas et al, 2013a ). The questions of whether ipRGCs co-store PACAP and whether the central projections of these cells are different in diurnal grass rats (either Nile or Sudanese) from those seen in nocturnal rodents have, however, not been addressed.…”

Light color importance for circadian entrainment in a diurnal (Octodon degus) and a nocturnal (Rattus norvegicus) rodent

“…Rats, as nocturnal animals, generally become more active in response to darkness or low light levels (positive masking) and less active in response to light (negative masking), whilst diurnal animals, such as degus, generally exhibit the opposite response. In any case, the masking effect was more pronounced under RGB (daylight) than under RGV light pulses (nightlight), which also agrees with the fact that ipRGC (sensitive to blue light) are also implicated in masking 44 , 69 . Again, these results could confirm that daylight, but not nightlight, is processed as true light input, activating the masking centres of the circadian system in both degus and rats.…”

“…Indeed, electrophysiological recordings showed differences in the photic responsiveness of SCN neurons in degus compared to rats 74 . With regard to the five different ipRGC subtypes (M1-M5), it has been reported that M1, which innervates the SCN (the main pacemaker) exists in a higher percentage (74%) in diurnal species, such as Arvicanthis ansorgei 44 as compared to nocturnal (30–44%), such as mice 42 , 43 , 45 . Thus, the greater cone contingent and higher percentage of M1 ipRGCs in diurnal rodents would explain why rats are unable to entrain under the input contrast between RGB vs .…”

The rat retina has five types of ganglion-cell photoreceptors

“…5), we compared the five ipRGC types’ melanopsin-based spiking responses to light. These analyses are beneficial to the field because MEA spike recordings have been used to compare the melanopsin photoresponses of different types of rodent ipRGCs (Karnas et al, 2013; Perez-Leighton et al, 2011; Tu et al, 2006; Tu et al, 2005) but since this method is done “blind”, researchers have been unable to assign cell types to their recordings. Establishing the correspondence between MEA- and whole-cell-recorded cell types would help overcome this problem.…”

“…Melanopsin-positive cells with M1- and M2-like morphologies were detected in Sudanian grass rat, and MEA recordings from neonatal retinas showed three varieties of melanopsin-based photoresponses, suggesting this species might have three or more ipRGC types (Karnas et al, 2013). In rabbit, melanopsin immunohistochemistry revealed not only M1 and M2 cells, but also bistratifying cells that were presumably M3 cells (Hoshi et al, 2009).…”