Abstract
Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) synchronize our biological clocks with the external light/dark cycle [1]. In addition to photoentrainment, they mediate the effects of light experience as a central modulator of mood, learning, and health [2]. This makes a complete account of the circuity responsible for ipRGCs' light responses essential to understanding their diverse roles in our well-being. Considerable progress has been made in understanding ipRGCs' melanopsin-mediated responses in rodents [3-5]. However, in primates, ipRGCs also have a rare blue-OFF response mediated by an unknown short-wavelength-sensitive (S)-cone circuit [6]. Identifying this S-cone circuit is particularly important because ipRGCs mediate many of the wide-ranging effects of short-wavelength light on human biology. These effects are often attributed to melanopsin, but there is evidence for an S-cone contribution as well [7, 8]. Here, we tested the hypothesis that the S-OFF response is mediated by the S-ON pathway through inhibitory input from an undiscovered S-cone amacrine cell. Using serial electron microscopy in the macaque retina, we reconstructed the neurons and synapses of the S-cone connectome, revealing a novel inhibitory interneuron, an amacrine cell, receiving excitatory glutamatergic input exclusively from S-ON bipolar cells. This S-cone amacrine cell makes highly selective inhibitory synapses onto ipRGCs, resulting in a blue-OFF response. Identification of the S-cone amacrine cell provides the missing component of an evolutionarily ancient circuit using spectral information for non-image forming visual functions.
Highlights
We confidently identified eight S-cones and 14 S-ON bipolar cells
Each of the 14 S-ON bipolar cells stratified in the innermost layer of the inner retina, sublamina 5 (S5), closest to the ganglion cell layer (GCL) [19] (Figures 1A and 1B)
We focused our efforts on M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) with somas in the GCL and dendrites stratifying primarily in the outermost layer of the inner retina, sublamina 1 (S1)
Summary
Patterson et al identify a new amacrine cell type in the primate retina with ‘‘blue’’ S-cone circuit input and targeted output to intrinsically photosensitive retinal ganglion cells (ipRGCs). This circuit may contribute to the effects of shortwavelength light on ipRGC downstream non-image-forming visual functions such as sleep, mood, and learning. 2020, Current Biology 30, 1269–1274 April 6, 2020 a 2020 The Authors.
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