Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision

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Summary

This study characterizes M4 intrinsically photosensitive retinal ganglion cells (ipRGCs) in mouse retina, revealing they correspond to ON α cells with large somata, robust ON responses, and projections to the dorsal lateral geniculate nucleus. These findings advance understanding of how melanopsin-expressing cells contribute not only to circadian/non-image-forming functions but also to conventional pattern vision, with implications for how different light qualities may engage distinct visual pathways.

Key Findings

M4 cells have smaller melanopsin-based intrinsic photocurrents than M1 and M2 cells, with melanopsin detectable only via strong immunohistochemical amplification, indicating weaker melanopsin expression.
M4 cells exhibit large receptive fields with ON-center, antagonistic OFF-surround organization and nonlinear spatial summation, distinguishing them functionally from other ipRGC subtypes.
M4 cells project to the dorsal lateral geniculate nucleus, indicating a role in image-forming (geniculocortical) vision that persists even in mice lacking functional rods and cones.
M4 dendrites stratify in the ON sublamina of the inner plexiform layer, positioned just distal to M2 dendrites and proximal to the ON cholinergic band, representing a distinct laminar pattern.
M4 cells show higher ultraviolet sensitivity in the ventral retina than dorsal retina, reflecting the topographic gradient of S- and M-cone opsin expression across the retina.