A Color Vision Circuit for Non-Image-Forming Vision in the Primate Retina.

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. • 3D reconstruction of the S-cone connectome revealed S-cone selective amacrine cells • S-cone amacrine cells receive excitatory input from only S-cone ON bipolar cells • S-cone amacrine cells make targeted inhibitory synapses onto ipRGCs • Resulting short-wavelength sensitivity is distinct from that mediated by melanopsin 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 short-wavelength light on ipRGC downstream non-image-forming visual functions such as sleep, mood, and learning. [ABSTRACT FROM AUTHOR]