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Abstract Objective . Retinal implants have been developed to electrically stimulate healthy retinal neurons in the progressively degenerated retina. Several stimulation approaches have been proposed to improve the visual percept induced in patients with retinal prostheses. We introduce a computational model capable of simulating the effects of electrical stimulation on retinal neurons. Leveraging this computational platform, we delve into the underlying mechanisms influencing the sensitivity of retinal neurons’ response to various stimulus waveforms. Approach . We implemented a model of spiking bipolar cells (BCs) in the magnocellular pathway of the primate retina, diffuse BC subtypes (DB4), and utilized our multiscale admittance method (AM)-NEURON computational platform to characterize the response of BCs to epiretinal electrical stimulation with monophasic, symmetric, and asymmetric biphasic pulses. Main results . Our investigations yielded four notable results: (a) the latency of BCs increases as stimulation pulse duration lengthens; conversely, this latency decreases as the current amplitude increases. (b) Stimulation with a long anodic-first symmetric biphasic pulse (duration > 8 ms) results in a significant decrease in spiking threshold compared to stimulation with similar cathodic-first pulses (from 98.2 to 57.5 µ A). (c) The hyperpolarization-activated cyclic nucleotide-gated channel was a prominent contributor to the reduced threshold of BCs in response to long anodic-first stimulus pulses. (d) Finally, extending the study to asymmetric waveforms, our results predict a lower BCs threshold using asymmetric long anodic-first pulses compared to that of asymmetric short cathodic-first stimulation. Significance . This study predicts the effects of several stimulation parameters on spiking BCs response to electrical stimulation. Of importance, our findings shed light on mechanisms underlying the experimental observations from the literature, thus highlighting the capability of the methodology to predict and guide the development of electrical stimulation protocols to generate a desired biological response, thereby constituting an ideal testbed for the development of electroceutical devices.
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Graphene-based microfluidic perforated microelectrode arrays for retinal electrophysiological studies
Perforated microelectrode arrays (pMEAs) have become essential tools for ex vivo retinal electrophysiological studies. pMEAs increase the nutrient supply to the explant and alleviate the accentuated curvature of the retina, allowing for long-term culture and intimate contacts between the retina and electrodes for electrophysiological measurements. However, commercial pMEAs are not compatible with in situ high-resolution optical imaging and lack the capability of controlling the local microenvironment, which are highly desirable features for relating function to anatomy and probing physiological and pathological mechanisms in retina. Here we report on microfluidic pMEAs (μpMEAs) that combine transparent graphene electrodes and the capability of locally delivering chemical stimulation. We demonstrate the potential of μpMEAs by measuring the electrical response of ganglion cells to locally delivered high K + stimulation under controlled microenvironments. Importantly, the capability for high-resolution confocal imaging of the retina tissue on top of the graphene electrodes allows for further analyses of the electrical signal source. The new capabilities provided by μpMEAs could allow for retinal electrophysiology assays to address key questions in retinal circuitry studies.
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- Award ID(s):
- 1810088
- PAR ID:
- 10431395
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 23
- Issue:
- 9
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 2193 to 2205
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d3lc00064h
