Diverse Signaling Mechanisms Employed by Intrinsically Photosensitive Retinal Ganglion Cells


The mammalian retina contains three classes of photoreceptors: rods, cones and the recently discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs express the photopigment melanopsin and were initially thought to be a homogeneous population of cells that drive subconscious visual behaviors such as circadian photoentrainment and pupil constriction. However, recent evidence has demonstrated that ipRGCs are in fact a heterogeneous population consisting of 6 subtypes (M1-M6), with some subtypes also mediating conscious visual perception (image-forming vision). Therefore, ipRGCs are a diverse population of RGC that regulates a wide range of physiological processes and behaviors. One common feature that all ipRGCs share is that they express the photopigment melanopsin. Our work has shown that melanopsin phototransduction activates unique signaling pathways in different ipRGC subtypes. Moreover, melanopsin phototransduction appears to be tuned to serve the specific behavioral role of each ipRGC subtype. Additionally, our work has shown that unlike most retinal ganglion cells, which release the excitatory neurotransmitter glutamate, a subpopulation of ipRGCs release the inhibitory neurotransmitter GABA. GABA release by this subpopulation of ipRGC tunes the light sensitivity of non-image forming visual behaviors. Thus, our work has expanded upon the current model of how ipRGCs signal light information and has shown that these signaling mechanisms play important roles in shaping behavior.

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