Divergent projection patterns of M1 ipRGC subtypes.

In addition to its well-known role in pattern vision, light influences a wide range of non-image forming, subconscious visual behaviors including circadian photoentrainment, sleep, mood, learning, and the pupillary light reflex. Each of these behaviors is thought to require input from the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC). Recent work has demonstrated that the M1 subtype of ipRGC can be further subdivided based on expression of the transcription factor Brn3b. Brn3b-positive M1 ipRGCs project to the olivary pretectal nucleus and are necessary for the pupillary light reflex, while Brn3b-negative M1 ipRGCs project to the suprachiasmatic nucleus (SCN) and are sufficient for circadian photoentrainment. However, beyond the circadian and pupil systems, little is known about the projection patterns of M1 ipRGC subtypes. Here we show that Brn3b-positive M1 ipRGCs comprise the majority of sparse M1 ipRGC inputs to the thalamus, midbrain, and hypothalamus. Our data demonstrate that very few brain targets receive convergent input from both M1 ipRGC subpopulations, suggesting that each subpopulation drives a specific subset of light-driven behaviors.

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