M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina
Journal
Journal of Neuroscience
Journal Volume
36
Journal Issue
27
Pages
7184 7197
Date Issued
2016
Author(s)
C. L. Prigge
P. T. Yeh
N. F. Liou
C. C. Lee
S. F. You
L. L. Liu
D. S. McNeill
K. S. Chew
S. Hattar
D. Q. Zhang
Abstract
Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs, with five subtypes named M1-M5) are a unique subclass of RGCs with axons that project directly to many brain nuclei involved in non-image-forming functions such as circadian photoentrainment and the pupillary light reflex. Recent evidence suggests that melanopsin-based signals also influence image-forming visual function, including light adaptation, but the mechanisms involved are unclear. Intriguingly, a small population ofM1ipRGCs have intraretinal axon collaterals that project toward the outer retina. Using genetic mouse models, we provide three lines of evidence showing that these axon collaterals make connections with upstream dopaminergic amacrine cells (DACs): (1) ipRGC signaling to DACs is blocked by tetrodotoxin both in vitro and in vivo, indicating that ipRGC-to-DAC transmission requires voltage-gated Na+ channels; (2) this transmission is partly dependent on N-type Ca2+ channels, which are possibly expressed in the axon collateral terminals of ipRGCs; and (3) fluorescence microscopy reveals that ipRGC axon collaterals make putative presynaptic contact with DACs. We further demonstrate that elimination of M1 ipRGCs attenuates light adaptation, as evidenced by an impaired electroretinogram b-wave from cones, whereas a dopamine receptor agonist can potentiate the cone-driven b-wave of retinas lacking M1 ipRGCs. Together, the results strongly suggest that ipRGCs transmit luminance signals retrogradely to the outer retina through the dopaminergic system and in turn influence retinal light adaptation. © 2016 the authors.
Subjects
Amacrine cell; Dopamine; Ganglion cell; Melanopsin; Retina; Vision
Other Subjects
melanopsin; tamoxifen; tetrodotoxin; beta galactosidase; Cnga3 protein, mouse; cyclic nucleotide gated channel; Gnat1 protein, mouse; guanine nucleotide binding protein alpha subunit; melanopsin; nerve protein; Pde6b protein, mouse; phosphodiesterase VI; protein c fos; scotopsin; sodium channel blocking agent; tetrodotoxin; transducin; tyrosine 3 monooxygenase; adult; amplitude modulation; animal experiment; animal model; animal tissue; Article; bleaching; confocal microscopy; controlled study; electroretinogram; female; fluorescence; immunofluorescence; immunohistochemistry; light adaptation; male; morphological adaptation; mouse; nonhuman; patch clamp technique; photostimulation; polymerase chain reaction; priority journal; retina ganglion cell; retrograde degeneration; signal transduction; synaptic membrane; vision; animal; C57BL mouse; classification; cytology; drug effects; excitatory postsynaptic potential; genetics; light; membrane potential; metabolism; newborn; physiology; retina; retina ganglion cell; transgenic mouse; vision; visual system; Animals; Animals, Newborn; beta-Galactosidase; Cyclic Nucleotide Phosphodiesterases, Type 6; Cyclic Nucleotide-Gated Cation Channels; Excitatory Postsynaptic Potentials; Female; GTP-Binding Protein alpha Subunits; Light; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Proto-Oncogene Proteins c-fos; Retina; Retinal Ganglion Cells; Rod Opsins; Sodium Channel Blockers; Tetrodotoxin; Transducin; Tyrosine 3-Monooxygenase; Vision, Ocular; Visual Pathways
Type
journal article