Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function

Abstract

Melanopsin imparts an intrinsic photosensitivity to a subclass of retinal ganglion cells (ipRGCs). Generally thought of as irradiance detectors, ipRGCs target numerous brain regions involved in non-image-forming vision. ipRGCs integrate their intrinsic, melanopsin-mediated light information with rod/cone signals relayed via synaptic connections to influence light-dependent behaviors. Early observations indicated diversity among these cells and recently several specific subtypes have been identified. These subtypes differ in morphological and physiological form, controlling separate functions that range from biological rhythm via circadian photoentrainment, to protective behavioral responses including pupil constriction and light avoidance, and even image-forming vision. In this Mini-Symposium review, we will discuss some recent findings that highlight the diversity in both form and function of these recently discovered atypical photoreceptors.

Figure 1.

ipRGC subtypes differ in morphology and site of dendritic fields. The outer nuclear layer (ONL) of the mammalian retina consists of rod and cone photoreceptors, which have synaptic connections to their respective rod (R) or cone (C) bipolar cells in the outer plexiform layer (OPL). The soma of bipolar, amacrine (DA, MA, and II) and horizontal (not depicted) cells are localized to the inner nuclear layer (INL). The INL and GCL (ganglion cell layer) are separated by the IPL, another region of dendritic–axonal interactions. The GCL contains retinal ganglion cells (not depicted) and the melanopsin-positive class of retinal ganglion cells, the ipRGCs. The classification of ipRGCs (M1, M2, M3, M4, and M5) is based on morphology and somatic and dendritic localization. The figure is modified from Do and Yau (2010).

Figure 2.

Morphology of M1, M2, and M3 ipRGCs and their physiological responses to light. Top, M1 (A), M2 (B), and M3 (C) ipRGCs are identified by their morphological characteristics and location of their dendritic arbors. M1 cells have dendritic ramifications in the OFF sublamina of the IPL, whereas M2 cells ramify in the ON sublamina. M3 cells have dendrites bistratifying in both the ON and OFF sublaminas of the IPL. Bottom, M1 cells have the largest intrinsic, melanopsin-mediated light-evoked response, while M2 and M3 cells have smaller light-evoked responses. Scale bars, 10 mV. The figure is modified from Schmidt and Kofuji (2011).

Figure 3.

ipRGC project to numerous central regions and play a role in shaping behavior. Central projections of M1 cells include the OPN, controlling pupil constriction, and the SCN, controlling circadian photoentrainment. Non-M1 cells, which currently include M2–M5 cells, send projections to the LGN and are involved in a rudimentary, low-acuity visual function. Additional sites of axonal terminations are located throughout the brain, influencing activity, sleep/wake states, nociception, and areas implicating novel functions of these cells.