scholarly journals Intrinsic light responses of retinal ganglion cells projecting to the circadian system

2003 ◽  
Vol 17 (9) ◽  
pp. 1727-1735 ◽  
Author(s):  
Erin J. Warren ◽  
Charles N. Allen ◽  
R. Lane Brown ◽  
David W. Robinson
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Circadian System ◽  
Retinal Ganglion ◽  
Light Responses

Photic Regulation of Circadian Rhythms and Voluntary Ethanol Intake: Role of Melanopsin-expressing Intrinsically Photosensitive Retinal Ganglion Cells

2020 ◽  
pp. 074873042098122
Author(s):  
Matthew C. Hartmann ◽  
Walter D. McCulley ◽  
Samuel T. Johnson ◽  
Corey S. Salisbury ◽  
Nikhil Vaidya ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Circadian System ◽  
Genetically Engineered ◽  
Ethanol Intake ◽  
Constant Darkness ◽  
Retinal Ganglion ◽  
Retinal Photoreceptors ◽  
Genetically Engineered Mouse Model ◽  
Lighting Regimen

“Non-image-forming” (NIF) effects of light are mediated primarily by a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment, melanopsin (OPN4). These NIF functions include circadian entrainment, pupillary reflexes, and photic effects on sleep, mood, and cognition. We recently reported that mice of multiple genotypes exhibit reduced voluntary ethanol intake under both constant darkness (DD) and constant light (LL) relative to standard light-dark (LD) conditions. In the present study, we sought to determine whether these effects are mediated by melanopsin-expressing ipRGCs and their potential relationship to photic effects on the circadian system. To this end, we examined the effects of environmental lighting regimen on both ethanol intake and circadian activity rhythms in a genetically engineered mouse model ( Opn4aDTA/aDTA) in which melanopsin expression is completely blocked while ipRGCs are progressively ablated due to activation of attenuated diphtheria toxin A (aDTA) transgene under the control of the Opn4 promoter. As expected from previous studies, Opn4aDTA/aDTA mice displayed dramatic attenuation of circadian photosensitivity, but surprisingly, showed identical suppression of ethanol intake under both DD and LL as that seen in controls. These results demonstrate that the effects of lighting regimen on voluntary ethanol intake are independent of melanopsin-expressing ipRGCs and ipRGC-mediated photic effects on the circadian system. Rather, these effects are likely mediated by classical retinal photoreceptors and central pathways.

scholarly journals Tailoring of the axon initial segment shapes the conversion of synaptic inputs into spiking output in OFF-α T retinal ganglion cells

2020 ◽  
Vol 6 (37) ◽  
pp. eabb6642
Author(s):  
Paul Werginz ◽  
Vineeth Raghuram ◽  
Shelley I. Fried
Keyword(s):  
Retinal Ganglion Cells ◽  
Initial Segment ◽  
Ganglion Cells ◽  
Axon Initial Segment ◽  
Retinal Ganglion ◽  
Light Responses ◽  
Synaptic Inputs ◽  
Dorsal Cells ◽  
Axon Initial Segments ◽  
Dorsal Retina

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.

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

2009 ◽  
Vol 102 (6) ◽  
pp. 3260-3269 ◽  
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.

scholarly journals Examination of zinc in the circadian system

2019 ◽  
Author(s):  
Mahtab Moshirpour ◽  
Amy S. Nakashima ◽  
Nicole Sehn ◽  
Victoria M. Smith ◽  
Richard H. Dyck ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Time Of Day ◽  
Circadian System ◽  
The Body ◽  
Mouse Retina ◽  
List Type ◽  
Retinal Ganglion ◽  
Night And Day ◽  
Zinc Levels

ABSTRACTZinc is a trace element that is essential for a large number of biological and biochemical processes in the body. In the nervous system zinc is packaged into synaptic vesicles by the ZnT3 transporter, and synaptic release of zinc can influence the activity of postsynaptic cells, either directly though its own cognate receptors, or indirectly by modulating activation of receptors for other neurotransmitters. Here, we explore the anatomical and functional aspects of zinc in the circadian system. Melanopsin-containing retinal ganglion cells in the mouse retina were found to colocalize ZnT3, indicating that they can release zinc at their synaptic targets. While the master circadian clock in the hamster suprachiasmatic nucleus (SCN) was found to contain, at best, sparse zincergic input, the intergeniculate leaflet (IGL) was found to have prominent zincergic input. Levels of zinc in these areas were not affected by time of day. Additionally, IGL zinc staining persisted following enucleation, indicating other prominent sources of zinc instead of, or in addition to, the retina. Neither enhancement nor chelation of free zinc at either the SCN or IGL altered circadian responses to phase-shifting light in hamsters. Finally, entrainment, free-running, and circadian responses to light were explored in mice lacking the ZnT3 gene. In every aspect explored, the ZnT3-KO mice were not significantly different from their wildtype counterparts. These findings highlight the presence of zinc in areas critical for circadian functioning but have yet to identify a role for zinc in these areas.HighlightsThe synaptic zinc transporter ZnT3 is found in melanopsin-containing retinal ganglion cells.While zinc input to the hamster SCN was found to be sparse at best, prominent zincergic staining was found throughout the IGL.Zinc levels in the SCN and IGL did not change between the night and day.Neither increasing nor decreasing zinc levels in either the SCN or IGL had an influence on circadian responses to light.Mice lacking the ZnT3 transporter did not differ from wildtype mice on a wide variety of circadian measures.

scholarly journals Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

2017 ◽  
Vol 149 (3) ◽  
pp. 335-353 ◽  
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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