Cellular properties of intrinsically photosensitive retinal ganglion cells during postnatal development

Abstract

Background: Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light and have been shown to mediate a broad variety of visual behaviors in adult animals. ipRGCs are also the first light sensitive cells in the developing retina, and have been implicated in a number of retinal developmental processes such as pruning of retinal vasculature and refinement of retinofugal projections. However, little is currently known about the properties of the six ipRGC subtypes during development, and how these cells act to influence retinal development. We therefore sought to characterize the structure, physiology, and birthdate of the most abundant ipRGC subtypes, M1, M2, and M4, at discrete postnatal developmental timepoints. Methods: We utilized whole cell patch clamp to measure the electrophysiological and morphological properties of ipRGC subtypes through postnatal development. We also used EdU labeling to determine the embryonic timepoints at which ipRGC subtypes terminally differentiate. Results: Our data show that ipRGC subtypes are distinguishable from each other early in postnatal development. Additionally, we find that while ipRGC subtypes terminally differentiate at similar embryonic stages, the subtypes reach adult-like morphology and physiology at different developmental timepoints. Conclusions: This work provides a broad assessment of ipRGC morphological and physiological properties during the postnatal stages at which they are most influential in modulating retinal development, and lays the groundwork for further understanding of the specific role of each ipRGC subtype in influencing retinal and visual system development.