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A noncanonical inhibitory circuit dampens behavioral sensitivity to light

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Science  01 May 2020:
Vol. 368, Issue 6490, pp. 527-531
DOI: 10.1126/science.aay3152

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Retinal ganglion cells that release GABA

Retinal ganglion cells (RGCs) communicate light signals from the retina to the brain and were previously considered to signal exclusively through release of excitatory neurotransmitters. There have been earlier hints of RGCs producing the inhibitory neurotransmitter γ-aminobutyric acid (GABA), but the specific cells have never been identified and their function was entirely unknown. Sonoda et al. found that a subpopulation of intrinsically photosensitive RGCs (ipRGCs) releases GABA (see the Perspective by Ding and Wei). Removal of GABA signaling from ipRGCs led to an increased light sensitivity of the pupillary light reflex and of circadian photoentrainment. GABA release thus moved the dynamic range of these non–image-forming behaviors to bright light intensities. These results explain why these behaviors are so much less sensitive to environmental lighting conditions than conscious visual perception.

Science, this issue p. 527; see also p. 471

Abstract

Retinal ganglion cells (RGCs) drive diverse, light-evoked behaviors that range from conscious visual perception to subconscious, non–image-forming behaviors. It is thought that RGCs primarily drive these functions through the release of the excitatory neurotransmitter glutamate. We identified a subset of melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) in mice that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at non–image-forming brain targets. GABA release from ipRGCs dampened the sensitivity of both the pupillary light reflex and circadian photoentrainment, thereby shifting the dynamic range of these behaviors to higher light levels. Our results identify an inhibitory RGC population in the retina and provide a circuit-level mechanism that contributes to the relative insensitivity of non–image-forming behaviors at low light levels.

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