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

Highlights

• Melanopsin enhances contrast sensitivity of M4 ipRGCs (ON alpha cells)

• Melanopsin phototransduction increases M4 ipRGC intrinsic excitability

• Melanopsin phototransduction closes leak potassium channels in M4 ipRGCs

• Melanopsin modulates M4 ipRGC physiology across a wide range of light intensities

Summary

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.