Article
Acknowledging non-monotonicity: working towards understanding electrical response types in mouse retinas
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Authors
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Archana Jalligampala
- Experimental Retinal Prosthetics Group at Institute for Ophthalmic Research University of Tübingen, Tübingen, Germany; Pupil Research Group at the Centre for Ophthalmology, University Hospitals Tübingen, Tübingen, Germany; Centre for Integrative Neuroscience at University of Tübingen, Tübingen, Germany
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C. Kelbsch
- Experimental Retinal Prosthetics Group at Institute for Ophthalmic Research University of Tübingen, Tübingen, Germany
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K. Stingl
- Pupil Research Group at the Centre for Ophthalmology, University Hospitals Tübingen, Tübingen, Germany
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T. Strasser
- Pupil Research Group at the Centre for Ophthalmology, University Hospitals Tübingen, Tübingen, Germany
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T. Peters
- Pupil Research Group at the Centre for Ophthalmology, University Hospitals Tübingen, Tübingen, Germany
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E. Zrenner
- Experimental Retinal Prosthetics Group at Institute for Ophthalmic Research University of Tübingen, Tübingen, Germany; Centre for Integrative Neuroscience at University of Tübingen, Tübingen, Germany
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B. Wilhelm
- Pupil Research Group at the Centre for Ophthalmology, University Hospitals Tübingen, Tübingen, Germany
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D.L. Rathbun
- Experimental Retinal Prosthetics Group at Institute for Ophthalmic Research University of Tübingen, Tübingen, Germany; Centre for Integrative Neuroscience at University of Tübingen, Tübingen, Germany
| Published: | November 30, 2017 |
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Outline
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Objective: A general assumption in the field is that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli creating a non-monotonic response function. While the field is progressing towards preferential activation of retinal neurons, in this study we identify optimal stimulation paradigms that can be used to activate many retinal neurons, when such electrical response types are part of the neuronal population.
Material and Methods: RGC (retinal ganglion cell) spiking responses were recorded in vitro from patches of WT (C57BL/6) and degenerated (rd10) mouse retina epiretinally, using a planar micro-electrode array (MEA, 60 electrodes, 200µm pitch, 30µm Ĝ). The stimulus was delivered via one of the MEA electrodes while the other electrodes recorded electrically-evoked responses. Stimuli consisted of square-wave, monophasic voltage pulses in incremental blocks (0.3V–2.5V,0.2Hz) with randomized pulse durations and sine-wave (0.3–2.5V, 1–20Hz). The stored data were processed & analyzed offline using spike sorting software and custom Matlab scripts to generate rastergrams, peri-stimulus time histograms, response curves and heat maps.
Results: Electrical responsiveness depends on both amplitude and duration/frequencies interacting non-linearly. Non-monotonicity was observed for both sinusoidal and pulsatile stimulation. Interestingly, such cells also responded to both polarities (anodic and cathodic) for pulsatile stimulation. Such response types were prominent with retinal degeneration.
Discussion: While monotonic response patterns were dominant for most RGCs, ignoring such non-monotonicity can lead to faulty conclusions about optimal stimulation, as well as obscure promising opportunities for RGC type-specific stimulation, considering there is a broad diversity of RGCs.
Acknowledgements: Kerstan Stiftung, Egon Schumacher-Stiftung, Pro-Retina; BMBF 031A308, DFG EXC307
