Spatial and temporal resolution of optogenetically recovered vision in ChR2-transduced mouse retina

M Reh, MJ Lee, J Schmierer… - Journal of Neural …, 2021 - iopscience.iop.org
M Reh, MJ Lee, J Schmierer, G Zeck
Journal of Neural Engineering, 2021iopscience.iop.org
Objective. Retinal ganglion cells (RGCs) represent an attractive target in vision restoration
strategies, because they undergo little degeneration compared to other retinal neurons.
Here we investigated the temporal and spatial resolution in adult photoreceptor-
degenerated (rd10) mouse retinas, where RGCs have been transduced with the optogenetic
actuator channelrhodopsin-2 (ChR2). Approach. The RGC spiking activity was recorded
continuously with a CMOS-based microelectrode array during a variety of photostimulation …
Objective
Retinal ganglion cells (RGCs) represent an attractive target in vision restoration strategies, because they undergo little degeneration compared to other retinal neurons. Here we investigated the temporal and spatial resolution in adult photoreceptor-degenerated (rd10) mouse retinas, where RGCs have been transduced with the optogenetic actuator channelrhodopsin-2 (ChR2).
Approach
The RGC spiking activity was recorded continuously with a CMOS-based microelectrode array during a variety of photostimulation protocols. The temporal resolution was assessed through Gaussian white noise stimuli and evaluated using a linear-nonlinear-Poisson model. Spatial sensitivity was assessed upon photostimulation with single rectangular pulses stepped across the retina and upon stimulation with alternating gratings of different spatial frequencies. Spatial sensitivity was estimated using logistic regression or by evaluating the spiking activity of independent RGCs.
Main results
The temporal resolution after photostimulation displayed an about ten times faster kinetics as compared to physiological filters in wild-type RGCs. The optimal spatial resolution estimated using the logistic regression model was 10 µm and 87 µm based on the population response. These values correspond to an equivalent acuity of 1.7 or 0.2 cycles per degree, which is better than expected from the size of RGCs' optogenetic receptive fields.
Significance
The high temporal and spatial resolution obtained by photostimulation of optogenetically transduced RGCs indicate that high acuity vision restoration may be obtained by photostimulation of appropriately modified RGCs in photoreceptor-degenerated retinas.
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