Temporal Structure in Spiking Patterns of Ganglion Cells Defines Perceptual Thresholds in Rodents with Subretinal Prosthesis

Overview

Journal Sci Rep

Specialty Science

Date 2018 Feb 18

PMID 29453455

Citations 13

Authors

Elton Ho

Henri Lorach

Georges Goetz

Florian Laszlo

Xin Lei

Theodore Kamins

Jean-Charles Mariani

Alexander Sher

Daniel Palanker

Affiliations

Soon will be listed here.

Abstract

Subretinal prostheses are designed to restore sight in patients blinded by retinal degeneration using electrical stimulation of the inner retinal neurons. To relate retinal output to perception, we studied behavioral thresholds in blind rats with photovoltaic subretinal prostheses stimulated by full-field pulsed illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to changes in brightness, with an average contrast threshold of 12%, which could not be explained by changes in the average RGC spiking rate. However, RGCs exhibited millisecond-scale variations in spike timing, even when the average rate did not change significantly. At 12% temporal contrast, changes in firing patterns of prosthetic response were as significant as with 2.3% contrast steps in visible light stimulation of healthy retinas. This suggests that millisecond-scale changes in spiking patterns define perceptual thresholds of prosthetic vision. Response to the last pulse in the stimulation burst lasted longer than the steady-state response during the burst. This may be interpreted as an excitatory OFF response to prosthetic stimulation, and can explain behavioral response to decrease in illumination. Contrast enhancement of images prior to delivery to subretinal prosthesis can partially compensate for reduced contrast sensitivity of prosthetic vision.

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References

Sekhar S, Jalligampala A, Zrenner E, Rathbun D . Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons. J Neural Eng. 2016; 13(4):046004. DOI: 10.1088/1741-2560/13/4/046004. View

Gollisch T, Meister M . Rapid neural coding in the retina with relative spike latencies. Science. 2008; 319(5866):1108-11. DOI: 10.1126/science.1149639. View

Li P, Gauthier J, Schiff M, Sher A, Ahn D, Field G . Anatomical identification of extracellularly recorded cells in large-scale multielectrode recordings. J Neurosci. 2015; 35(11):4663-75. PMC: 4363392. DOI: 10.1523/JNEUROSCI.3675-14.2015. View

Troy J, Enroth-Cugell C . X and Y ganglion cells inform the cat's brain about contrast in the retinal image. Exp Brain Res. 1993; 93(3):383-90. DOI: 10.1007/BF00229354. View

Zrenner E, Bartz-Schmidt K, Benav H, Besch D, Bruckmann A, Gabel V . Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci. 2010; 278(1711):1489-97. PMC: 3081743. DOI: 10.1098/rspb.2010.1747. View

Chichilnisky E . A simple white noise analysis of neuronal light responses. Network. 2001; 12(2):199-213. View

Goetz G, Smith R, Lei X, Galambos L, Kamins T, Mathieson K . Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information. Invest Ophthalmol Vis Sci. 2015; 56(12):7186-94. PMC: 4640473. DOI: 10.1167/iovs.15-17566. View

Sekirnjak C, Hottowy P, Sher A, Dabrowski W, Litke A, Chichilnisky E . Electrical stimulation of mammalian retinal ganglion cells with multielectrode arrays. J Neurophysiol. 2006; 95(6):3311-27. DOI: 10.1152/jn.01168.2005. View

Wong W, Su X, Li X, Cheung C, Klein R, Cheng C . Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014; 2(2):e106-16. DOI: 10.1016/S2214-109X(13)70145-1. View

10.

Lorach H, Goetz G, Mandel Y, Lei X, Galambos L, Kamins T . Performance of photovoltaic arrays in-vivo and characteristics of prosthetic vision in animals with retinal degeneration. Vision Res. 2014; 111(Pt B):142-8. PMC: 4375097. DOI: 10.1016/j.visres.2014.09.007. View

11.

Stingl K, Bartz-Schmidt K, Besch D, Chee C, Cottriall C, Gekeler F . Subretinal Visual Implant Alpha IMS--Clinical trial interim report. Vision Res. 2015; 111(Pt B):149-60. DOI: 10.1016/j.visres.2015.03.001. View

12.

Jensen R, Rizzo 3rd J . Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode. Exp Eye Res. 2006; 83(2):367-73. DOI: 10.1016/j.exer.2006.01.012. View

13.

Panzeri S, Brunel N, Logothetis N, Kayser C . Sensory neural codes using multiplexed temporal scales. Trends Neurosci. 2010; 33(3):111-20. DOI: 10.1016/j.tins.2009.12.001. View

14.

Davis M . Fear-potentiated startle in rats. Curr Protoc Neurosci. 2008; Chapter 8:Unit 8.11A. DOI: 10.1002/0471142301.ns0811as14. View

15.

Lorach H, Kung J, Beier C, Mandel Y, Dalal R, Huie P . Development of Animal Models of Local Retinal Degeneration. Invest Ophthalmol Vis Sci. 2015; 56(8):4644-52. PMC: 4516014. DOI: 10.1167/iovs.14-16011. View

16.

Mante V, Frazor R, Bonin V, Geisler W, Carandini M . Independence of luminance and contrast in natural scenes and in the early visual system. Nat Neurosci. 2005; 8(12):1690-7. DOI: 10.1038/nn1556. View

17.

Kim S, Sadda S, PEARLMAN J, Humayun M, de Juan Jr E, Melia B . Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Retina. 2002; 22(4):471-7. DOI: 10.1097/00006982-200208000-00012. View

18.

Lorach H, Goetz G, Smith R, Lei X, Mandel Y, Kamins T . Photovoltaic restoration of sight with high visual acuity. Nat Med. 2015; 21(5):476-82. PMC: 4601644. DOI: 10.1038/nm.3851. View

19.

Lorach H, Lei X, Galambos L, Kamins T, Mathieson K, Dalal R . Interactions of Prosthetic and Natural Vision in Animals With Local Retinal Degeneration. Invest Ophthalmol Vis Sci. 2015; 56(12):7444-50. PMC: 5110201. DOI: 10.1167/iovs.15-17521. View

20.

Greschner M, Field G, Li P, Schiff M, Gauthier J, Ahn D . A polyaxonal amacrine cell population in the primate retina. J Neurosci. 2014; 34(10):3597-606. PMC: 3942577. DOI: 10.1523/JNEUROSCI.3359-13.2014. View