Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

Abstract

Over the past two decades there have been significant advances in our understanding of both the anatomy and function of the melanopsin system. It has become clear that rather than acting as a simple irradiance detector the melanopsin system is in fact far more complicated. The range of behavioural systems known to be influenced by melanopsin activity is increasing with time, and it is now clear that melanopsin contributes not only to multiple non-image forming systems but also has a role in visual pathways. How melanopsin is capable of driving so many different behaviours is unclear, but recent evidence suggests that the answer may lie in the diversity of melanopsin light responses and the functional specialisation of photosensitive retinal ganglion cell (pRGC) subtypes. In this review, we shall overview the current understanding of the melanopsin system, and evaluate the evidence for the hypothesis that individual pRGC subtypes not only perform specific roles, but are functionally specialised to do so. We conclude that while, currently, the available data somewhat support this hypothesis, we currently lack the necessary detail to fully understand how the functional diversity of pRGC subtypes correlates with different behavioural responses, and ultimately why such complexity is required within the melanopsin system. What we are lacking is a cohesive understanding of how light responses differ between the pRGC subtypes (based not only on anatomical classification but also based on their site of innervation); how these diverse light responses are generated, and most importantly how these responses relate to the physiological functions they underpin.

Figure 1

(a) Innervations of M1–M5 type pRGCs in the mouse brain as revealed by intravitreal delivery of AAV2 viral vectors containing lox.STOP.lox.mCherry into the retina of Opn4.Cre mice. (b) Images showing the morphology of pRGC subtypes of the mouse retina. M1, M2, and M3-type pRGCs are labelled using anti-melanopsin antibodies. M4 - and M5-type pRGCs are identified by expression of EYFP in Opn4.Cre.EYFP mice and the lack of detectable melanopsin labelling. (c) Examples of types III and II melanopsin responses recorded from the adult mouse retina using multiple electrode arrays, typical of M1 - and non-M1-type pRGCs, respectively. Black bars indicate duration of light pulse (30 s, 480 nm, 15.1 log photons/cm²/s). dLGN, dorsal lateral geniculate nucleus; GCL, ganglion cell layer; IGL, intergeniculate leaflet; INL, inner nuclear layer; IPL, inner plexiform layer; OFF, OFF layer of the inner plexiform layer; ON, ON layer of the inner plexiform layer; OPN, olivary pretectal nucleus; SCN, suprachiasmatic nucleus; vLGN, ventral lateral geniculate nucleus.