title: Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones.
abstract: Intrinsically photosensitive retinal ganglion cells (iprgcs) are depolarized by light by two mechanisms: directly, through activation of their photopigment melanopsin; and indirectly through synaptic circuits driven by rods and cones. To learn more about the rod and cone circuits driving ipRGCs, we made multielectrode array (MEA) and patch-clamp recordings in wildtype and genetically modified mice. Rod-driven ON inputs to ipRGCs proved to be as sensitive as any reaching the conventional ganglion cells. These signals presumably pass in part through the primary rod pathway, involving rod bipolar cells and AII amacrine cells coupled to ON cone bipolar cells through gap junctions. Consistent with this interpretation, the sensitive rod ON input to ipRGCs was eliminated by pharmacological or genetic disruption of gap junctions, as previously reported for conventional ganglion cells. A presumptive cone input was also detectable as a brisk, synaptically mediated ON response that persisted after disruption of rod ON pathways. This was roughly three log units less sensitive than the rod input. Spectral analysis revealed that both types of cones, the M- and S-cones, contribute to this response and that both cone types drive ON responses. This contrasts with the blue-OFF, yellow-ON chromatic opponency reported in primate ipRGCs. The cone-mediated response was surprisingly persistent during steady illumination, echoing the tonic nature of both the rod input to ipRGCs and their intrinsic, melanopsin-based phototransduction. These synaptic inputs greatly expand the dynamic range and spectral bandpass of the non-image-forming visual functions for which ipRGCs provide the principal retinal input.
authors.affiliation: Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Shijun
authors.initials: S
authors.lastname: Weng
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Estevez
authors.forename: David M
authors.initials: DM
authors.lastname: Berson
mesh_terms: D000818:Animals; D002469:Cell Separation; D017630:Connexins / Q000172:deficiency / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012684:Sensory Thresholds / Q000528:radiation effects; D013569:Synapses / Q000378:metabolism / Q000528:radiation effects; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D000097004:Gap Junction delta-2 Protein