Article
Efficiency of combined optogenetic and electric stimulation depending on amplitude and waveform of electric stimulation in mouse retina
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Authors
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Hyeonhee Roh
- Brain Science Institute, Korea Institute of Science and Technology (KIST), South Korea; School of Electrical Engineering, College of Engineering, Korea University, South Korea
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J. Kang
- School of Electrical Engineering, College of Engineering, Korea University, South Korea
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H.-M. Lee
- School of Electrical Engineering, College of Engineering, Korea University, South Korea
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M. Im
- Brain Science Institute, Korea Institute of Science and Technology (KIST), South Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), South Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, South Korea
| Published: | May 9, 2025 |
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Outline
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Objective: Combining optogenetic and electric stimulation was proposed to enhance the spatial resolution while reducing the optical power. In this study, we aimed to evaluate the effectiveness of hybrid stimulation in retinal neurons.
Materials and Methods: AAV2-CAG-ChR2(H134R)-EGFP was intravitreally injected into the eyeballs of mice (C57BL/6J). Spiking activities of retinal ganglion cells (RGCs) were recorded using cell-attached patch-clamping. First, two light intensities from a 470 nm LED were applied for optogenetic-only stimulation. Second, hybrid optogenetic and electric stimulation was delivered with electric pulses of –5 μA square, –10 μA square, or –20 μA ramp (all 100 ms in duration).
Results: With the high intensity optical stimulation, hybrid stimulation with –5 μA square, –10 μA square, and –20 μA ramp elicited 0.36, 2.13, and 2.13 more spikes compared to the optogenetic-only stimulation (n=13, 22, and 5, respectively). At the low intensity optical stimulation, spike counts increased by 1.10, 1.83, and 2.37, respectively. Probably due to more supplied charges, the –10 μA square showed a higher increment in spike counts than the –5 μA square. Interestingly, the –20 μA ramp current produced more spikes at the low light intensity compared to the –10 μA square pulse even with the same amount charge.
Discussion: Our findings show that the effectiveness of hybrid stimulation is dependent on both optical intensity and electric pulse parameters. Optimization of pulse amplitude and waveform in hybrid stimulation may enhance neural activation at low light levels, improving optogenetic vision restoration approaches.
Acknowledgment: This work was supported in part by KIST institutional grants (Nos. 2E33231 and 2E32921), and in part by the National R&D Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (Nos. 2020R1C1C1006065, 2022M3E5E8017395, RS-2023-00302397, and RS-2024-00398460).
