Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

Sang Baek Ryu; Jang Hee Ye; Jong Seung Lee; Yong Sook Goo; Chi Hyun Kim; Kyung Hwan Kim

doi:10.4196/kjpp.2009.13.6.443

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Ryu, Ye, Lee, Goo, Kim, and Kim: Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

Original Article

Korean J Physiol Pharmacol 2009;13(6):443-448.

Published online: 18 February 2009

DOI: https://doi.org/10.4196/kjpp.2009.13.6.443

Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by Repetitive Pulse Stimulation

Sang Baek Ryu¹, Jang Hee Ye², Jong Seung Lee¹, Yong Sook Goo², Chi Hyun Kim¹, Kyung Hwan Kim^1,

¹Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju 220-710, Korea

²Department of Physiology, Chungbuk National University School of Medicine, Cheongju 361-763, Korea

Corresponding to: Kyung Hwan Kim, Department of Biomedical Engineering, College of Health Science, Yonsei University, 234, Maeji-ri, Heungup-myun, Wonju 220-710, Korea. (Tel) 82-33-760-2932, (Fax) 82-33-763-1953, (E-mail) khkim0604@yonsei.ac.kr

Received 28 October 2009 Revised 24 November 2009 Accepted 28 November 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

For successful visual perception by visual prosthesis using electrical stimulation, it is essential to develop an effective stimulation strategy based on understanding of retinal ganglion cell (RGC) responses to electrical stimulation. We studied RGC responses to repetitive electrical stimulation pulses to develop a stimulation strategy using stimulation pulse frequency modulation. Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached to a planar multi-electrode array (MEA) and RGC spike trains responding to electrical stimulation pulse trains with various pulse frequencies were observed. RGC responses were strongly dependent on inter-pulse interval when it was varied from 500 to 10 ms. Although the evoked spikes were suppressed with increasing pulse rate, the number of evoked spikes were >60% of the maximal responses when the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the modulation of evoked RGC firing rates while increasing the pulse frequency from 1 to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for modulation of RGC response strength. RGC response strength monotonically and linearly increased within the stimulation frequency of 1∼9 Hz. The results suggest that the evoked neural activities of RGCs in degenerated retina can be reliably controlled by pulse frequency modulation, and may be used as a stimulation strategy for visual neural prosthesis.

Keywords: Degenerated retina, Microelectrode arrray (MEA), Retinal ganglion cells, Retinal implant, Electrical stimulation, Visual neural prosthesis

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Fig. 1.

(A) A typical raw waveform of spontaneous retinal activity. Rhythmic oscillatory behavior with ∼10 Hz frequency is clearly observable from the background. (B) A typical raw waveform recorded under stimulation. (C) Electrically-evoked RGC spike waveforms derived from the raw recording in (B) by highpass filtering (second order Butterworth filter, cutoff frequency: 100 Hz).

Fig. 2.

Short-latency RGC spikes. (A) Inter-pulse interval: 500 ms, (B) inter-pulse interval: 10 ms (Thin solid line: before TTX treatment. Thick dotted line: after TTX treatment. Template subtraction result: indicated by arrows.).

Fig. 3.

Electrically-evoked RGC responses when a pair of pulses was applied. (A) Inter-pulse interval: 500 ms. (B) Inter-pulse interval: 100 ms. (C) Inter-pulse interval: 50 ms. (D) Inter-pulse interval: 10 ms.

Fig. 4.

The number of RGC spikes evoked by second pulses in the pulse pairs plotted as a function of inter-pulse interval (500∼50 ms). Each data point was obtained from the average of 75 RGCs. Error bar denotes standard error.

Fig. 5.

The RGC response strength (number of spikes normalized to the values for single pulse stimulation) evoked by each pulse of five successive pulses plotted as a function of inter-pulse interval (500∼70 ms). The results were obtained from 75 RGCs.

Fig. 6.

The RGC response strength as a function of pulse frequency. The results were obtained from 14 RGCs.

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