Neurophysics, NMI Natural and Medical Sciences Institute at the University Tübingen, Reutlingen 72770, Germany.
Graduate School of Neural Information Processing/International Max Planck Research School, Tübingen, Germany.
J Neural Eng. 2021 Apr 6;18(5). doi: 10.1088/1741-2552/abe39a.
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).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.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 10m and 87m 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.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.
视网膜神经节细胞 (RGCs) 在视觉恢复策略中是一个很有吸引力的靶点，因为与其他视网膜神经元相比，它们的退化程度较小。在这里，我们研究了成年光感受器退行性变 (rd10) 小鼠视网膜中的时间和空间分辨率，其中 RGC 已经被光遗传学效应器通道视紫红质-2 (ChR2) 转导。通过基于 CMOS 的微电极阵列，在各种光刺激方案下，连续记录 RGC 的尖峰活动。通过高斯白噪声刺激评估时间分辨率，并使用线性-非线性-泊松模型进行评估。通过在视网膜上用单个矩形脉冲逐步进行光刺激以及用不同空间频率的交替光栅进行刺激，评估空间灵敏度。使用逻辑回归或评估独立 RGC 的尖峰活动来估计空间灵敏度。与野生型 RGC 中的生理滤波器相比，光刺激后的时间分辨率显示出约十倍的更快动力学。使用逻辑回归模型估计的最佳空间分辨率基于群体反应分别为 10m 和 87m。这些值对应于 1.7 或 0.2 个每度的等效视力，优于 RGC 光遗传学感受野大小所预期的。光遗传学转导的 RGC 光刺激获得的高时间和空间分辨率表明，通过适当修饰的光感受器退行性变视网膜中的 RGC 光刺激，可能获得高分辨率视力恢复。
