scholarly journals Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators

2013 ◽  
Vol 109 (7) ◽  
pp. 1979-1988 ◽  
Author(s):  
Andrew C. Weitz ◽  
Matthew R. Behrend ◽  
Nan Sook Lee ◽  
Ronald L. Klein ◽  
Vince A. Chiodo ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Viral Vector ◽  
Ganglion Cells ◽  
High Specificity ◽  
Multielectrode Arrays ◽  
Limited Information ◽  
Stimulus Pulse ◽  
Photoreceptor Layer ◽  
Calcium Indicators ◽  
Genetically Encoded Calcium Indicators

Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.

Electrical Stimulation of Mammalian Retinal Ganglion Cells With Multielectrode Arrays

2006 ◽  
Vol 95 (6) ◽  
pp. 3311-3327 ◽  
Author(s):  
Chris Sekirnjak ◽  
Pawel Hottowy ◽  
Alexander Sher ◽  
Wladyslaw Dabrowski ◽  
A. M. Litke ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Ganglion Cells ◽  
Small Diameter ◽  
Multielectrode Arrays ◽  
Electrode Arrays ◽  
Charge Densities ◽  
Disk Electrodes ◽  
Low Charge ◽  
Large Groups ◽  
Stimulation Of

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micrometers. To increase the spatial resolution of artificial sight, electrodes much smaller than those currently in use are desirable. In this study, we stimulated and recorded ganglion cells in isolated pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal arrays of 61 platinum disk electrodes with diameters between 6 and 25 μm, spaced 60 μm apart. Charge-balanced current pulses evoked one or two spikes at latencies as short as 0.2 ms, and typically only one or a few recorded ganglion cells were stimulated. Application of several synaptic blockers did not abolish the evoked responses, implying direct activation of ganglion cells. Threshold charge densities were typically <0.1 mC/cm2 for a pulse duration of 100 μs, corresponding to charge thresholds of <100 pC. Stimulation remained effective after several hours and at high frequencies. To show that closely spaced electrodes can elicit independent ganglion cell responses, we used the multielectrode array to stimulate several nearby ganglion cells simultaneously. From these data, we conclude that electrical stimulation of mammalian retina with small-diameter electrode arrays is achievable and can provide high temporal and spatial precision at low charge densities. We review previous epiretinal stimulation studies and discuss our results in the context of 32 other publications, comparing threshold parameters and safety limits.

scholarly journals Biophysical model of axonal stimulation in epiretinal visual prostheses

2018 ◽  
Author(s):  
Michael Beyeler
Keyword(s):  
Electrical Stimulation ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Small Population ◽  
Biophysical Model ◽  
Retinal Ganglion ◽  
Stimulus Pulse ◽  
Perceptual Distortions ◽  
Retinal Response

AbstractVisual prostheses aim to restore vision to people blinded from degenerative photoreceptor diseases by electrically stimulating surviving neurons in the retina. However, a major challenge with epiretinal prostheses is that they may accidentally activate passing axon fibers, causing severe perceptual distortions. To investigate the effect of axonal stimulation on the retinal response, we developed a computational model of a small population of morphologically and biophysically detailed retinal ganglion cells, and simulated their response to epiretinal electrical stimulation. We found that activation thresholds of ganglion cell somas and axons varied systematically with both stimulus pulse duration and electrode-retina distance. These findings have important implications for the improvement of stimulus encoding methods for epiretinal prostheses.

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

2012 ◽  
Vol 107 (10) ◽  
pp. 2742-2755 ◽  
Author(s):  
Max Eickenscheidt ◽  
Martin Jenkner ◽  
Roland Thewes ◽  
Peter Fromherz ◽  
Günther Zeck
Keyword(s):  
Electrical Stimulation ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Biophysical Model ◽  
Retinal Neurons ◽  
Direct Stimulation ◽  
Tungsten Electrode ◽  
Partial Restoration ◽  
Low Amplitude ◽  
Stimulation Of

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array—insulated by an inert oxide—allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.

Genetically Encoded Calcium Indicators

2008 ◽  
Vol 108 (5) ◽  
pp. 1550-1564 ◽  
Author(s):  
Marco Mank ◽  
Oliver Griesbeck
Keyword(s):  
Calcium Indicators ◽  
Genetically Encoded Calcium Indicators

Survival-Promoting Effect of Electrical Stimulation on Axotomized Retinal Ganglion Cells

2003 ◽  
pp. 156-159
Author(s):  
Tomomitsu Miyoshi ◽  
Takeshi Morimoto ◽  
Toru Yakura ◽  
Yuka Okazaki ◽  
Takuji Kurimoto ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Promoting Effect
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