Dendritic Calcium Signaling in ON and OFF Mouse Retinal Ganglion Cells

Margolis, David J.; Gartland, Andrew J.; Euler, Thomas; Detwiler, Peter B.

doi:10.1523/jneurosci.5694-09.2010

Cited by 55 publications

(57 citation statements)

References 38 publications

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“…Recent data has shown that while both ON and OFF RGCs express high voltage activated Ca 2+ channels, only OFF cells also express the LVA Ca 2+ channels (Margolis et al 2010). The results presented here show that many of the differences in intrinsic electrophysiology of ON and OFF cells can be explained on this basis.…”

Section: Discussionsupporting

confidence: 59%

“…Differences in response properties of ON and OFF RGCs are also shaped by their intrinsic electrophysiological properties, although only limited data are available (Margolis and Detwiler 2007;Margolis et al 2010Margolis et al , 2008. Margolis and Detwiler (2007) have examined the response of ON and OFF RGCs to currentclamp stimuli in mice when synaptic input was blocked.…”

Section: Introductionmentioning

confidence: 99%

“…A number of ionic currents have been considered as potential mechanisms underlying these differences in intrinsic electrophysiology of ON and OFF RGCs (Margolis and Detwiler 2007;Margolis et al 2010Margolis et al , 2008. The potential currents include the persistent Na + current, I NaP , the low voltage activated (LVA) Ca 2+ current, I T , and the hyperpolarization activated mixed cation current, I h .…”

Section: Introductionmentioning

confidence: 99%

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Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

2011

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ON and OFF retinal ganglion cells (RGCs) display differences in their intrinsic electrophysiology: OFF cells maintain spontaneous activity in the absence of any input, exhibit subthreshold membrane potential oscillations, rebound excitation and burst firing; ON cells require excitatory input to drive their activity and display none of the aforementioned phenomena. The goal of this study was to identify and characterize ionic currents that explain these intrinsic electrophysiological differences between ON and OFF RGCs. A mathematical model of the electrophysiological properties of ON and OFF RGCs was constructed and validated using published patch-clamp data from isolated intact mouse retina. The model incorporates three ionic currents hypothesized to play a role in generating behaviors that are different between ON and OFF RGCs. These currents are persistent Na( + ), I (NaP), hyperpolarization-activated, I (h), and low voltage activated Ca(2 + ), I (T), currents. Using computer simulations of Hodgkin-Huxley type neuron with a single compartment model we found two distinct sets of I (NaP), I (h), I (T) conductances that correspond to ON and OFF RGCs populations. Simulations indicated that special properties of I (T) explain the differences in intrinsic electrophysiology between ON and OFF RGCs examined here. The modelling shows that the maximum conductance of I (T) is higher in OFF than in ON cells, in agreement with recent experimental data.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

2011

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“…In contrast, ON cells exhibit no endogenous activity and display none of the aforementioned phenomena [55]. Later, the same group determined the presence of a low-voltage activated (LVA) Ca 2+ channel in OFF cells that does not exist in ON cells [56]. A computational modeling study by Kamaneva et.…”

Section: Discussionmentioning

confidence: 99%

Differential responses to high-frequency electrical stimulation in ON and OFF retinal ganglion cells

2014

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Objective The field of retinal prosthetics for artificial vision has advanced considerably in recent years, however clinical outcomes remain inconsistent. The performance of retinal prostheses is likely limited by the inability of electrical stimuli to preferentially activate different types of retinal ganglion cell (RGC). Approach Here we examine the response of rabbit RGCs to high-frequency stimulation, using biphasic pulses applied at 2000 pulses per second. Responses were recorded using cell-attached patch clamp methods, and stimulation was applied epiretinally via a small cone electrode. Results When prolonged stimulus trains were applied to OFF-Brisk Transient (BT) RGCs, the cells exhibited a non-monotonic relationship between response strength and stimulus amplitude; this response pattern was different from those elicited previously by other electrical stimuli. When the amplitude of the stimulus was modulated transiently from a non-zero baseline amplitude, ON-BT and OFF-BT cells exhibited different activity patterns: ON cells showed an increase in activity while OFF cells exhibited a decrease in activity. Using a different envelope to modulate the amplitude of the stimulus, we observed the opposite effect: ON cells exhibited a decrease in activity while OFF cells show an increase in activity. Significance As ON and OFF RGCs often exhibit opposing activity patterns in response to light stimulation, this work suggests that high-frequency electrical stimulation of RGCs may be able to elicit responses that are more physiological than traditional pulsatile stimuli. Additionally, the prospect of an electrical stimulus capable of cell-type specific selective activation has broad applications throughout the fields of neural stimulation and neuroprostheses.

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“…In the same WT OFF RGCs, rebound excitation, another intrinsic property, can be evoked by application of negative current in the absence of synaptic input and a role for low-voltage gated (LVA) Ca 2+ channels has been proposed (Margolis et al, 2010 . This could result from absence of GlyRα2-mediated inhibition of a tonic inhibitory input onto either the OFF RGC or its presynaptic OFF BC.…”

Section: Mechanisms That Contribute To Post Stimulus Rebound Excitatimentioning

confidence: 99%

Glycine receptor alpha subunit (GlyRa) specific inhibition contributes to ganglion cell signaling in mouse retina.

Zhang¹

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Dendritic Calcium Signaling in ON and OFF Mouse Retinal Ganglion Cells

Abstract: Retinal ganglion cells (RGCs

Cited by 55 publications

References 38 publications

Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

Differential responses to high-frequency electrical stimulation in ON and OFF retinal ganglion cells

Glycine receptor alpha subunit (GlyRa) specific inhibition contributes to ganglion cell signaling in mouse retina.

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