Melanopsin Contributions to Irradiance Coding in the Thalamo-Cortical Visual System

Abstract

Neurophysiological and anatomical studies identify melanopsin expressing retinal ganglion cells (mRGCs) as a major source of information in the mouse visual system.

Abstract

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ∼40% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration.

Author Summary

The ability to convert light into electrical signals in the mammalian retina has traditionally been thought to occur through only two types of photoreceptors, the rods and cones. However, this ability also extends to a small number of neurons expressing the protein melanopsin. To date these melanopsin retinal ganglion cells (mRGCs) have been thought to act as photoreceptors primarily for those brain regions regulating subconscious responses to ambient light, such as pupil size. In this study, we provide evidence that mRGCs also contribute extensively to conventional visual pathways. We use a newly developed strategy to characterize the brain regions to which these cells project and then directly monitor visually evoked neural activity in these target regions. We find that mRGCs allow the mouse visual system to faithfully encode ambient illumination over at least a million-fold range and to continue to show light responses even in the absence of all rods and cones. These data reveal a new role for mRGCs during normal vision and suggest that mRGCs could make a significant contribution to assessing brightness and supporting vision even in people with advanced retinal degeneration.