Crosstalk: The diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image‐forming and non‐image‐forming vision

Abstract

Melanopsin ganglion cells have defied convention since their discovery almost 20 years ago. In the years following, many types of these intrinsically photosensitive retinal ganglion cells (ipRGCs) have emerged. In the mouse retina, there are currently six known types (M1–M6) of melanopsin ganglion cells, each with unique morphology, mosaics, connections, physiology, projections, and functions. While melanopsin‐expressing cells are usually associated with behaviors like circadian photoentrainment and the pupillary light reflex, the characterization of multiple types has demonstrated a reach that may extend far beyond non‐image‐forming vision. In fact, studies have shown that individual types of melanopsin ganglion cells have the potential to impact image‐forming functions like contrast sensitivity and color opponency. Thus, the goal of this review is to summarize the morphological and functional aspects of the six known types of melanopsin ganglion cells in the mouse retina and to highlight their respective roles in non‐image‐forming and image‐forming vision. Although many melanopsin ganglion cell types do project to image‐forming brain targets, it is important to note that this is only the first step in determining their influence on image‐forming vision. Even so, the visual system has canonically been divided into these two functional realms and melanopsin ganglion cells have begun to challenge the boundary between them, providing an overlap of visual information that is complementary rather than redundant. Further studies on these ganglion cell photoreceptors will no doubt continue to illustrate an ever‐expanding role for melanopsin ganglion cells in image‐forming vision.

Circadian Photoentrainment in Mice and Humans

“…Since their identification, pRGCs have been shown to contribute to a broad range of non-image forming (NIF) responses to light [ 29 ], including: pupillary light response (PLR) [ 47 ]; the acute suppression of locomotor activity (negative masking) [ 79 ]; sleep induction [ 80 , 81 , 82 , 83 ]; levels of alertness [ 84 , 85 , 86 ]; light aversion [ 87 , 88 ]; and influencing mood-related behaviors, such as levels of anxiety and cognitive function [ 85 , 86 , 89 ]. More recently it has been discovered that melanopsin contributes not only to NIF responses to light but also visual pathways, challenging the previous model of separate image forming (IF) and non-image forming (NIF) systems [ 90 , 91 , 92 ]. For example, melanopsin-based pRGCs convey light to the visual centers of the brain regarding overall levels of environmental light, and perform roles in irradiance coding and brightness discrimination [ 93 , 94 , 95 , 96 ], contrast detection [ 97 ] and adaptation of visual responses [ 98 ], whilst also possibly providing spatial information and potentially supporting basic pattern vision [ 99 , 100 ].…”

“…At least five and possibly six pRGC subtypes have been identified, termed M1–M5 [ 50 , 99 , 112 , 113 , 114 ]. They differ in their morphology and retinal connections, and show light responses with distinct properties [ 92 , 115 , 116 ]). In addition, pRGC subtypes seem to project to different brain regions [ 99 , 112 , 113 , 117 , 118 , 119 ], and as a result, may mediate different physiological responses to light [ 114 , 115 ].…”

Light/Clock Influences Membrane Potential Dynamics to Regulate Sleep States

“…A subset of ipRGCs can also be found in the area of the retinal edge called the ciliary marginal zone, inner plexiform layer (IPL) (116). Six classes of ipRGCs (M1-M6) have been characterized (117,118), which are mainly dictated by where they stratify in the IPL and the synaptic input from bipolar cells [reviewed in (119)]. For example, M1 ipRGCs stratify in the outer sublamina of the IPL, where they form excitatory synapses with bipolar cells that detect light fluctuations; M2, M4, and M5 cells stratify solely in the inner sublamina; and M3 and M6 cells are bistratified in both layers (118,120).…”

Retinal ganglion cell interactions shape the developing mammalian visual system

“…Interestingly, one type of RGC, the M1 ipRGC, extends its dendrites beyond the IPL during development, and is poised to regulate more than just its synaptic partners. ipRGC types are defined by their dendritic structure and lamination pattern, soma size, melanopsin expression and projections to central retinal targets (Sondereker et al, 2020). M1 ipRGCs terminate their dendrites in the outer IPL (Provencio et al, 2002), but during postnatal development, they extend their dendrites towards the outer retina (Fig.…”