Functional subtypes of rodent melanopsin ganglion cells switch roles between night and day illumination.

ABSTRACT

Intrinsically photosensitive retinal ganglion cells (ipRGCs), contain the photopigment melanopsin, and influence both image and non-image forming behaviors. Despite being categorized into multiple types (M1-M6), physiological variability within these types suggests our current understanding of ipRGCs is incomplete. We used multi-electrode array (MEA) recordings and unbiased cluster analysis under synaptic blockade to identify 8 functional clusters of ipRGCs, each with distinct photosensitivity and response timing. We used Cre mice to drive the expression of channelrhodopsin in SON-ipRGCs, enabling the localization of distinct ipRGCs in the dorsal retina. Additionally, we conducted a retrospective unbiased cluster analysis of ipRGC photoresponses to light stimuli across scotopic, mesopic, and photopic intensities, aimed at activating both rod and cone inputs to ipRGCs. Our results revealed shared and distinct synaptic inputs to the identified functional clusters, demonstrating that ipRGCs encode visual information with high fidelity at low light intensities, but poorly at photopic light intensities, when melanopsin activation is highest. Collectively, our findings support a framework with at least 8 functional subtypes of ipRGCs, each encoding luminance with distinct spike outputs, highlighting the inherent functional diversity and complexity of ipRGCs and suggesting a reevaluation of their contributions to retinal function and visual perception under varying light conditions.