| Summary: | Summary: Intrinsically photosensitive retinal ganglion cells of the M1 type encode environmental irradiance for functions that include circadian and pupillary regulation. Their distinct role, morphology, and molecular markers indicate that they are stereotyped circuit elements, but their physiological uniformity has not been investigated in a systematic fashion. We have profiled the biophysical parameters of mouse M1s and found that extreme variation is their hallmark. Most parameters span 1–3 log units, and the full range is evident in M1s that innervate brain regions serving divergent functions. Biophysical profiles differ among cells possessing similar morphology and between neighboring M1s recorded simultaneously. Variation in each parameter is largely independent of that in others, allowing for flexible individualization. Accordingly, a common stimulus drives heterogeneous spike outputs across cells. By contrast, a population of directionally selective retinal ganglion cells appeared physiologically uniform under similar conditions. Thus, M1s lack biophysical constancy and send diverse signals downstream. : Emanuel et al. demonstrate that a type of sensory cell with a defined role and morphology nevertheless exhibits log units of variation in its biophysical parameters. Variation drives functional individualization, even in spike outputs, and is fully available to downstream brain regions serving divergent functions. Keywords: cell type, melanopsin, photoreceptor, retinal ganglion cell, phototransduction, heterogeneity, membrane excitability, directionally selective retinal ganglion cell, Hb9
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