Stanford University School of Medicine, Stanford University, Stanford, CA, United States of America.
Neurosurgery, Stanford University, Stanford, CA, United States of America.
J Neural Eng. 2023 Aug 31;20(4). doi: 10.1088/1741-2552/ace657.
. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly. Here we demonstrate an inference approach that exploits intrinsic electrophysiological features of primate RGCs.First, ON-parasol and OFF-parasol RGC types were identified using their intrinsic electrical features in large-scale multi-electrode recordings from macaque retina. Then, the electrically inferred somatic location, inferred cell type, and average linear-nonlinear-Poisson model parameters of each cell type were used to infer a light response model for each cell. The accuracy of the cell type classification and of reproducing measured light responses with the model were evaluated.A cell-type classifier trained on 246 large-scale multi-electrode recordings from 148 retinas achieved 95% mean accuracy on 29 test retinas. In five retinas tested, the inferred models achieved an average correlation with measured firing rates of 0.49 for white noise visual stimuli and 0.50 for natural scenes stimuli, compared to 0.65 and 0.58 respectively for models fitted to recorded light responses (an upper bound). Linear decoding of natural images from predicted RGC activity in one retina showed a mean correlation of 0.55 between decoded and true images, compared to an upper bound of 0.81 using models fitted to light response data.These results suggest that inference of RGC light response properties from intrinsic features of their electrical activity may be a useful approach for high-fidelity sight restoration. The overall strategy of first inferring cell type from electrical features and then exploiting cell type to help infer natural cell function may also prove broadly useful to neural interfaces.
视网膜植入物旨在通过刺激视网膜神经节细胞(RGCs)来恢复因光感受器变性而失明的个体的视力。使用这些设备复制高清晰度视力可能需要推断植入视网膜中不同 RGC 类型的自然光反应,而无法直接测量它们。在这里,我们展示了一种利用灵长类动物 RGC 的固有电生理特征的推断方法。
首先,在从猕猴视网膜的大规模多电极记录中利用其固有电特征来识别 ON 伞形和 OFF 伞形 RGC 类型。然后,使用每个细胞类型的电推断体细胞位置、推断细胞类型和平均线性非线性泊松模型参数来推断每个细胞的光反应模型。评估了细胞类型分类的准确性和使用模型重现测量光反应的准确性。
在 148 个视网膜的 246 个大规模多电极记录上训练的细胞类型分类器在 29 个测试视网膜上的平均准确率达到 95%。在五个测试的视网膜中,与记录的光反应拟合的模型相比,推断模型对白色噪声视觉刺激的平均相关性为 0.49,对自然场景刺激的平均相关性为 0.50,分别为 0.65 和 0.58。在一个视网膜中,从预测的 RGC 活动中对自然图像进行线性解码,解码图像与真实图像之间的平均相关性为 0.55,而使用拟合到光反应数据的模型的上限为 0.81。
这些结果表明,从电活动的固有特征推断 RGC 光反应特性可能是实现高保真视力恢复的一种有用方法。从电特征推断细胞类型,然后利用细胞类型来帮助推断自然细胞功能的总体策略,对于神经接口也可能具有广泛的应用价值。