Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and project to central targets, allowing them to contribute to both image-forming and non-image forming vision. Recent studies have highlighted chemical and electrical synapses between ipRGCs and neurons of the inner retina, suggesting a potential influence from the melanopsin-born signal to affect visual processing at an early stage of the visual pathway. We investigated melanopsin responses in ganglion cell layer (GCL) neurons of both intact and dystrophic mouse retinas using 256 channel multi-electrode array (MEA) recordings. A wide 200 μm inter-electrode spacing enabled a pan-retinal visualization of melanopsin’s influence upon GCL activity. Upon initial stimulation of dystrophic retinas with a long, bright light pulse, over 37% of units responded with an increase in firing (a far greater fraction than can be expected from the anatomically characterized number of ipRGCs). This relatively widespread response dissipated with repeated stimulation even at a quite long inter-stimulus interval (ISI; 120 s), to leave a smaller fraction of responsive units (<10%; more in tune with the predicted number of ipRGCs). Visually intact retinas appeared to lack such widespread melanopsin responses indicating that it is a feature of dystrophy. Taken together, our data reveal the potential for anomalously widespread melanopsin responses in advanced retinal degeneration. These could be used to probe the functional reorganization of retinal circuits in degeneration and should be taken into account when using retinally degenerate mice as a model of disease.

Highlights

  • Soon after their discovery as a new class of photoreceptor in the retina (Berson et al, 2002; Hattar et al, 2002), melanopsin expressing intrinsically photosensitive retinal ganglion cells were suggested to have intra-retinal projections (Sekaran et al, 2003)

  • Since our recordings are of Intrinsically photosensitive retinal ganglion cells (ipRGCs) Signal to Other RGCs spiking cells in the retinal ganglion cell layer (GCL), there is a risk that we may be reporting the firing of action potentials from these cells

  • We identify the potential for melanopsin to initiate spiking light responses in a high number of nonphotosensitive neurons of the dystrophic retina

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Summary

Introduction

Soon after their discovery as a new class of photoreceptor in the retina (Berson et al, 2002; Hattar et al, 2002), melanopsin expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) were suggested to have intra-retinal projections (Sekaran et al, 2003). It has since become clear that ipRGCs impact retinal activity through at least two pathways: gap junction signaling to wide ipRGCs Signal to Other RGCs field amacrine cells (ACs) (Muller et al, 2010; Reifler et al, 2015) and excitatory projections to dopaminergic ACs (Zhang et al, 2008). These circuits mean that, ipRGCs represent a small fraction (

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