Spontaneous Oscillatory Rhythms in the Degenerating Mouse Retina Modulate Retinal Ganglion Cell Responses to Electrical Stimulation

Goo, Yong Sook,Park, Dae Jin,Ahn, Jung Ryul,Senok, Solomon S. Frontiers Media S.A. 2015 Frontiers in cellular neuroscience Vol.9 No.-

<P>Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (<I>rd1</I> and <I>rd10</I> mice), where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs). Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC) spikes on the trough of the oscillatory LFP. In <I>rd1</I> mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in <I>rd10</I> mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to <I>rd10</I> mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.</P>

The advantage of topographic prominence-adopted filter for the detection of short-latency spikes of retinal ganglion cells

안정열,최명환,김광수,Solomon S. Senok,조동일,구교인,구용숙 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.5

Electrical stimulation through retinal prosthesis elicits both short and long-latency retinal ganglion cell (RGC) spikes. Because the short-latency RGC spike is usually obscured by electrical stimulus artifact, it is very important to isolate spike from stimulus artifact. Previously, we showed that topographic prominence (TP) discriminator based algorithm is valid and useful for artifact subtraction. In this study, we compared the performance of forward backward (FB) filter only vs. TP-adopted FB filter for artifact subtraction. From the extracted retinae of rd1 mice, we recorded RGC spikes with 8×8 multielectrode array (MEA). The recorded signals were classified into four groups by distances between the stimulation and recording electrodes on MEA (200-400, 400-600, 600-800, 800-1000 μm). Fifty cathodic phase-1st biphasic current pulses (duration 500 μs, intensity 5, 10, 20, 30, 40, 50, 60 μA) were applied at every 1 sec. We compared false positive error and false negative error in FB filter and TP-adopted FB filter. By implementing TP-adopted FB filter, short-latency spike can be detected better regarding sensitivity and specificity for detecting spikes regardless of the strength of stimulus and the distance between stimulus and recording electrodes.

Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration (rd1) mice

안건노,안정열,김재형,조경록,구교인,Solomon S. Senok,구용숙 대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

A retinal prosthesis is being developed for the restoration of vision in patients with retinitispigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electricalstimulation parameters for the prosthesis is one of the most important elements for the developmentof a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasicpulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinaldegeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches wereplaced ganglion cell layer down onto an 8×8 multielectrode array (MEA) and RGC responses wererecorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the samewith symmetric pulse but the amplitude of 2nd phase of the pulse is less than 10 μA and chargebalanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration)modulation, duration (or amplitude) of the pulse was fixed to 500 μs (30 μA), changing the intensities(or duration) from 2 to 60 μA (60 to 1000 μ s). RGCs were classified as response-positive when PSTHshowed multiple (3∼4) peaks within 400 ms post stimulus and the number of spikes was at least30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulatedboth with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses producedsignificantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetryof the pulse.

The advantage of topographic prominence-adopted filter for the detection of short-latency spikes of retinal ganglion cells

Ahn, Jungryul,Choi, Myoung-Hwan,Kim, Kwangsoo,Senok, Solomon S.,Cho, Dong-il Dan,Koo, Kyo-in,Goo, Yongsook The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.5

Electrical stimulation through retinal prosthesis elicits both short and long-latency retinal ganglion cell (RGC) spikes. Because the short-latency RGC spike is usually obscured by electrical stimulus artifact, it is very important to isolate spike from stimulus artifact. Previously, we showed that topographic prominence (TP) discriminator based algorithm is valid and useful for artifact subtraction. In this study, we compared the performance of forward backward (FB) filter only vs. TP-adopted FB filter for artifact subtraction. From the extracted retinae of rd1 mice, we recorded RGC spikes with $8{\times}8$ multielectrode array (MEA). The recorded signals were classified into four groups by distances between the stimulation and recording electrodes on MEA (200-400, 400-600, 600-800, $800-1000{\mu}m$). Fifty cathodic phase-$1^{st}$ biphasic current pulses (duration $500{\mu}s$, intensity 5, 10, 20, 30, 40, 50, $60{\mu}A$) were applied at every 1 sec. We compared false positive error and false negative error in FB filter and TP-adopted FB filter. By implementing TP-adopted FB filter, short-latency spike can be detected better regarding sensitivity and specificity for detecting spikes regardless of the strength of stimulus and the distance between stimulus and recording electrodes.

Topographic prominence discriminator for the detection of short-latency spikes of retinal ganglion cells

Choi, Myoung-Hwan,Ahn, Jungryul,Park, Dae Jin,Lee, Sang Min,Kim, Kwangsoo,Cho, Dong-il Dan,Senok, Solomon S,Koo, Kyo-in,Goo, Yong Sook IOP 2017 Journal of neural engineering Vol.14 No.1

<P> <I>Objective</I>. Direct stimulation of retinal ganglion cells in degenerate retinas by implanting epi-retinal prostheses is a recognized strategy for restoration of visual perception in patients with retinitis pigmentosa or age-related macular degeneration. Elucidating the best stimulus-response paradigms in the laboratory using multielectrode arrays (MEA) is complicated by the fact that the short-latency spikes (within 10 ms) elicited by direct retinal ganglion cell (RGC) stimulation are obscured by the stimulus artifact which is generated by the electrical stimulator. <I>Approach</I>. We developed an artifact subtraction algorithm based on topographic prominence discrimination, wherein the duration of prominences within the stimulus artifact is used as a strategy for identifying the artifact for subtraction and clarifying the obfuscated spikes which are then quantified using standard thresholding. <I>Main results</I>. We found that the prominence discrimination based filters perform creditably in simulation conditions by successfully isolating randomly inserted spikes in the presence of simple and even complex residual artifacts. We also show that the algorithm successfully isolated short-latency spikes in an MEA-based recording from degenerate mouse retinas, where the amplitude and frequency characteristics of the stimulus artifact vary according to the distance of the recording electrode from the stimulating electrode. By ROC analysis of false positive and false negative first spike detection rates in a dataset of one hundred and eight RGCs from four retinal patches, we found that the performance of our algorithm is comparable to that of a generally-used artifact subtraction filter algorithm which uses a strategy of local polynomial approximation (SALPA). <I>Significance</I>. We conclude that the application of topographic prominence discrimination is a valid and useful method for subtraction of stimulation artifacts with variable amplitudes and shapes. We propose that our algorithm may be used as stand-alone or supplementary to other artifact subtraction algorithms like SALPA.</P>

Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration<i> (rd1) </i>mice

Kun No Ahn,Jeong Yeol Ahn,Jae-hyung Kim,Kyoungrok Cho,Kyo-in Koo,Solomon S. Senok,Yong Sook Goo 대한생리학회-대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an 8×8 multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than 10 <i>μ</i>A and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to 500 <i>μ</i>s (30 <i>μ</i>A), changing the intensities (or duration) from 2 to 60 <i>μ</i>A (60 to 1000 <i>μ</i>s). RGCs were classified as response-positive when PSTH showed multiple (3∼4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.

Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration (rd1) mice

Ahn, Kun No,Ahn, Jeong Yeol,Kim, Jae-Hyung,Cho, Kyoungrok,Koo, Kyo-In,Senok, Solomon S.,Goo, Yong Sook The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an $8{\times}8$ multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than $10{\mu}A$ and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to $500{\mu}s$($30{\mu}A$), changing the intensities (or duration) from 2 to $60{\mu}A$(60 to $1000{\mu}s$). RGCs were classified as response-positive when PSTH showed multiple (3~4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.