Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells.
Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs' rod/cone-driven responses depends neither on melanopsin nor onN-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells' responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca2+as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or transient light responses. Parenthetically, we find evidence in both mice and rats that the kinetics of light-induced mGluR6 deactivation determines whether an ON bipolar cell responds tonically or transiently to light.
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.
Xiwu
X
Zhao
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.
Aaron N
http://orcid.org/0000-0003-3885-2826
AN
Reifler
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.
Melanie M
http://orcid.org/0000-0001-8792-7658
MM
Schroeder
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.
Elizabeth R
ER
Jaeckel
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105.
Andrew P
AP
Chervenak
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105 kwoon@umich.edu.|Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48105.
Kwoon Y
http://orcid.org/0000-0001-9279-7827
KY
Wong
D000818:Animals; D002118:Calcium / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D000099210:Melanopsin
D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017299:Rod Opsins; D000099210:Melanopsin