Overlapping morphological and functional properties between M4 and M5 intrinsically photosensitive retinal ganglion cells

Abstract

Multiple retinal ganglion cell (RGC) types in the mouse retina mediate pattern vision by responding to specific features of the visual scene. The M4 and M5 melanopsinexpressing, intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes are two RGC types that are thought to play major roles in pattern vision. The M4 ipRGCs overlap in population with ON-alpha RGCs, while M5 ipRGCs were recently reported to exhibit opponent responses to different wavelengths of light (color opponency).Despite their seemingly distinct roles in visual processing, previous reports have suggested that these two populations may exhibit overlap in their morphological and functional properties, which calls into question whether these are in fact distinct RGC types. Here, we show that M4 and M5 ipRGCs are distinct morphological classes of ipRGCs, but they cannot be exclusively differentiated based on color opponency and dendritic morphology as previously reported. Instead, we find that M4 and M5 ipRGCs can only be distinguished based on soma size and the number of dendritic branch points in combination with SMI-32 immunoreactivity. These results have important implications for clearly defining RGC types and their roles in visual behavior. K E Y W O R D S alpha, color opponent, ipRGC, melanopsin, retina, retinal ganglion cell,

Characterization of Tbr2‐expressing retinal ganglion cells

“…M4 ipRGCs have been characterized as having the largest dendritic arbor area and soma diameter among all known ipRGCs (Estevez et al, 2012) and a recent study identified them intersectionally in Opn4 Cre : Z/EG mice using coincidental GFP and SMI32 signals (Sonoda et al, 2019). In 37 AP‐stained retinas, we analyzed 15 these M4‐like Tbr2 + RGCs with large dendritic arbors and somata (arbor diameter: 327.95 ± 48.51 μm; soma diameter: 19.28 ± 3.49 μm; N = 15) and relatively loose dendritic arbors (Figure 7(a,b′)).…”

Gbx2 Identifies Two Amacrine Cell Subtypes with Distinct Molecular, Morphological, and Physiological Properties

“…If S5-Gbx2 ACs are the CRH-1 subtype, as hypothesized above, we would expect that they provide inhibition onto “sustained” suppressed-by-contrast (SbC) RGCs and On aRGCs (also known as the M4 subtype of intrinsically photosensitive RGCs [ipRGCs]) ( Estevez et al, 2012 ; Jacoby and Schwartz, 2018 ; Jacoby et al, 2015 ; Park et al, 2018 ). Sublamina 5 also contains the dendrites of the M2, M3, and M5 subtypes of ipRGCs, which are involved in visual modalities involved in light avoidance, pupillary reflex, and circadian rhythm behaviors ( Schmidt et al, 2011 ; Sonoda et al, 2020 ).…”

Photoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina

“…5E3). Cells studied based on these properties and subsequently visualized by confocal microscopy exhibited morphological properties characteristic of M5 ipRGCs: monostratified dendritic arbors within the inner margin of the IPL, dense dendritic branching, and relatively small dendritic and somatic diameters (Stabio et al, 2018;Sonoda et al, 2020) (see Fig. 4D1).…”