Effect of Glycinergic Blockade on Light Responses of Frog Retinal Ganglion Cells

Recently, mouse OFF-α transient (OFF-α T) retinal ganglion cells (RGCs) were shown to display a gradient of light responses as a function of position along the dorsal-ventral axis; response differences were correlated to differences in the level of excitatory presynaptic input. Here, we show that postsynaptic differences between cells also make a strong contribution to response differences. Cells in the dorsal retina had longer axon initial segments (AISs)—the greater number of Nav1.6 channels in longer AISs directly mediates higher rates of spiking and helps avoid depolarization block that terminates spiking in ventral cells with shorter AISs. The pre- and postsynaptic specializations that shape the output of OFF-α T RGCs interact in different ways: In dorsal cells, strong inputs and the long AISs are both necessary to generate their strong, sustained spiking outputs, while in ventral cells, weak inputs or the short AISs are both sufficient to limit the spiking signal.

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Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

Journal of Neurophysiology ◽

10.1152/jn.00663.2009 ◽

2009 ◽

Vol 102 (6) ◽

pp. 3260-3269 ◽

Cited By ~ 65

Author(s):

Chris Sekirnjak ◽

Clare Hulse ◽

Lauren H. Jepson ◽

Pawel Hottowy ◽

Alexander Sher ◽

...

Keyword(s):

Electrical Stimulation ◽

Retinal Ganglion Cells ◽

Vision Loss ◽

Ganglion Cells ◽

Transgenic Rat ◽

Direct Electrical Stimulation ◽

Retinal Ganglion ◽

Photoreceptor Degeneration ◽

Wild Type ◽

Light Responses

Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of ∼10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60–70% at all ages. Surprisingly, thresholds (∼0.05 mC/cm2) and latencies (∼0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.

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Effects of a Metabotropic Glutamate 1 Receptor Antagonist on Light Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa

PLoS ONE ◽

10.1371/journal.pone.0079126 ◽

2013 ◽

Vol 8 (10) ◽

pp. e79126 ◽

Cited By ~ 4

Author(s):

Ralph J. Jensen

Keyword(s):

Retinitis Pigmentosa ◽

Receptor Antagonist ◽

Retinal Ganglion Cells ◽

Rat Model ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Light Responses ◽

Metabotropic Glutamate

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Faculty Opinions recommendation of Relative contributions of bipolar cell and amacrine cell inputs to light responses of ON, OFF and ON-OFF retinal ganglion cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1005725.68106 ◽

2002 ◽

Author(s):

Richard H Masland

Keyword(s):

Retinal Ganglion Cells ◽

Bipolar Cell ◽

Amacrine Cell ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Light Responses

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Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

The Journal of General Physiology ◽

10.1085/jgp.201611720 ◽

2017 ◽

Vol 149 (3) ◽

pp. 335-353 ◽

Cited By ~ 8

Author(s):

Xiwu Zhao ◽

Aaron N. Reifler ◽

Melanie M. Schroeder ◽

Elizabeth R. Jaeckel ◽

Andrew P. Chervenak ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Presynaptic Inhibition ◽

Ganglion Cells ◽

Glutamate Uptake ◽

Bipolar Cells ◽

Retinal Ganglion ◽

Light Responses ◽

Comprehensive Survey ◽

Underlying Mechanisms ◽

Kinetics Of

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 on N-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.

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Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells

Visual Neuroscience ◽

10.1017/s0952523813000199 ◽

2013 ◽

Vol 30 (4) ◽

pp. 175-182 ◽

Cited By ~ 45

Author(s):

HANNAH R. JOO ◽

BETH B. PETERSON ◽

DENNIS M. DACEY ◽

SAMER HATTAR ◽

SHIH-KUO CHEN

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Plexiform Layer ◽

Small Subset ◽

Inner Plexiform Layer ◽

Retinal Ganglion ◽

Light Responses ◽

Genetic Method ◽

Axon Collaterals ◽

The Brain

AbstractRetinal ganglion cells (RGCs), the output neurons of the retina, have axons that project via the optic nerve to diverse targets in the brain. Typically, RGC axons do not branch before exiting the retina and thus do not provide it with synaptic feedback. Although a small subset of RGCs with intraretinal axon collaterals has been previously observed in human, monkey, cat, and turtle, their function remains unknown. A small, more recently identified population of RGCs expresses the photopigment melanopsin. These intrinsically photosensitive retinal ganglion cells (ipRGCs) transmit an irradiance-coding signal to visual nuclei in the brain, contributing both to image-forming vision and to several nonimage-forming functions, including circadian photoentrainment and the pupillary light reflex. In this study, using melanopsin immunolabeling in monkey and a genetic method to sparsely label the melanopsin cells in mouse, we show that a subgroup of ipRGCs have axons that branch en route to the optic disc, forming intraretinal axon collaterals that terminate in the inner plexiform layer of the retina. The previously described collateral-bearing population identified by intracellular dye injection is anatomically indistinguishable from the collateral-bearing melanopsin cells identified here, suggesting they are a subset of the melanopsin-expressing RGC type and may therefore share its functional properties. Identification of an anatomically distinct subpopulation in mouse, monkey, and human suggests this pathway may be conserved in these and other species (turtle and cat) with intraretinal axon collaterals. We speculate that ipRGC axon collaterals constitute a likely synaptic pathway for feedback of an irradiance signal to modulate retinal light responses.

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