Survey of electrically evoked responses in the retina - stimulus preferences and oscillation among neurons

David Tsai,Nigel H Lovell,John W Morley,Gregg J Suaning

doi:10.1038/s41598-017-14357-1

David Tsai, Nigel H Lovell + Show 2 more

Open Access

https://doi.org/10.1038/s41598-017-14357-1

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Abstract

Electrical stimulation is an important tool in neuroscience research and clinically. In the retina, extensive work has revealed how the retinal ganglion cells respond to extracellular electrical stimulation. But little is known about the responses of other neuronal types, and more generally, how the network responds to stimulation. We conducted a survey of electrically evoked responses, over a range of pulse amplitudes and pulse widths, for 21 cell types spanning the inner two layers of the rabbit retina. It revealed: (i) the evoked responses of some neurons were charge insensitive; (ii) pulse-width sensitivity varied between cell types, allowing preferential recruitment of cell types; and (iii) 10–20 Hz damped oscillations across retinal layers. These oscillations were generated by reciprocal excitatory / inhibitory synapses, at locations as early as the cone-horizontal-cell synapses. These results illustrate at cellular resolution how a network responds to extracellular stimulation, and could inform the development of bioelectronic implants for treating blindness.

Highlights

Electrical stimulation has a long application history in neuroscience research, for inferring the function of neurons individually and across brain areas[1,2]
Analyses of this data revealed that: (i) the response amplitude of two wide-field neurons and horizontal cells did not scale with stimulus charge; (ii) sensitivity to pulse width differed between neuronal types, offering the possibility for preferential recruitment; and (iii) 10–20 Hz damped oscillations occurred across retinal layers following electrical stimulation
We assembled a library of morphology, light evoked responses and electrically evoked responses for 21 cell types across the inner two layers of the rabbit retina, encompassing all major interneuron types, including horizontal cells, bipolar cells, amacrine cells, as well as the retinal ganglion cells (RGCs)

Summary

Introduction

Electrical stimulation has a long application history in neuroscience research, for inferring the function of neurons individually and across brain areas[1,2]. The handful of studies that directly recorded from these neurons have relied on slicing the retina[21,22] or delaminating the photoreceptor layer[23] This compromises network connectivity and involves stimulating-electrode-to-tissue placements that do not correspond to clinical arrangements. We combined intracellular electrophysiology and morphological characterization to compile a survey of electrically evoked responses, for 21 neuronal types spanning the inner two retinal layers, and over a range of stimulus configurations Analyses of this data revealed that: (i) the response amplitude of two wide-field neurons and horizontal cells did not scale with stimulus charge; (ii) sensitivity to pulse width differed between neuronal types, offering the possibility for preferential recruitment; and (iii) 10–20 Hz damped oscillations occurred across retinal layers following electrical stimulation. The ubiquity of such connectivity implies that damped oscillatory responses may occur following electrical stimulation in other parts of the central nervous system

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