Melanopsin Phototransduction Is Repurposed by ipRGC Subtypes to Shape the Function of Distinct Visual Circuits

Melanopsin is expressed in distinct types of intrinsically photosensitive retinal ganglion cells (ipRGCs), which drive behaviors from circadian photoentrainment to contrast detection. A major unanswered question is how the same photopigment, melanopsin, influences such vastly different functions. Here we show that melanopsin's role in contrast detection begins in the retina, via direct effects on M4 ipRGC (ON alpha RGC) signaling. This influence persists across an unexpectedly wide range of environmental light levels ranging from starlight to sunlight, which considerably expands the functional reach of melanopsin on visual processing. Moreover, melanopsin increases the excitability of M4 ipRGCs via closure of potassium leak channels, a previously unidentified target of the melanopsin phototransduction cascade. Strikingly, this mechanism is selective for image-forming circuits, as M1 ipRGCs (involved in non-image forming behaviors), exhibit a melanopsin-mediated decrease in excitability. Thus, melanopsin signaling is repurposed by ipRGC subtypes to shape distinct visual behaviors. Sonoda et al. identify leak potassium channels as the major target of melanopsin phototransduction in M4 ipRGCs/ON alpha retinal ganglion cells. Melanopsin-dependent closure of these channels enhances cell excitability and contrast sensitivity across a wide range of light intensities.Fil: Sonoda, Takuma. Northwestern University; Estados UnidosFil: Lee, Seul Ki. Northwestern University; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. National Institute of Environmental Health Sciences; Estados UnidosFil: Schmidt, Tiffany M.. Northwestern University; Estados Unido