Wu Eric G, Rudzite Andra M, Bohlen Martin O, Li Peter H, Kling Alexandra, Cooler Sam, Rhoades Colleen, Brackbill Nora, Gogliettino Alex R, Shah Nishal P, Madugula Sasidhar S, Sher Alexander, Litke Alan M, Field Greg D, Chichilnisky E J
Department of Electrical Engineering, Stanford University, Stanford, CA, United States of America.
Department of Neurobiology, Duke University, Durham, NC, United States of America.
J Neural Eng. 2025 Jul 9;22(4). doi: 10.1088/1741-2552/ade344.
Identifying neuronal cell types and their biophysical properties based on their extracellular electrical features is a major challenge for experimental neuroscience and for the development of high-resolution brain-machine interfaces. One example is identification of retinal ganglion cell (RGC) types and their visual response properties, which is fundamental for developing future electronic implants that can restore vision.The electrical image (EI) of a RGC, or the mean spatio-temporal voltage footprint of its recorded spikes on a high-density electrode array, contains substantial information about its anatomical, morphological, and functional properties. However, the analysis of these properties is complex because of the high-dimensional nature of the EI. We present a novel optimization-based algorithm to decompose EI into a low-dimensional, biophysically-based representation: the temporally-shifted superposition of three learned basis waveforms corresponding to spike waveforms produced in the somatic, dendritic and axonal cellular compartments.The decomposition was evaluated using large-scale multi-electrode recordings from the macaque retina. The decomposition accurately localized the somatic and dendritic compartments of the cell. The imputed dendritic fields of RGCs correctly predicted the location and shape of their visual receptive fields. The inferred waveform amplitudes and shapes accurately identified the four major primate RGC types (ON and OFF midget and parasol cells) substantially more accurately than previous approaches.These findings contribute to more accurate inference of RGC types and their original light responses based purely on their electrical features, with potential implications for vision restoration technology.
基于细胞外电特征来识别神经元细胞类型及其生物物理特性,这对实验神经科学以及高分辨率脑机接口的发展而言是一项重大挑战。一个例子是视网膜神经节细胞(RGC)类型及其视觉反应特性的识别,这对于开发能够恢复视力的未来电子植入物至关重要。RGC的电图像(EI),即其在高密度电极阵列上记录的尖峰的平均时空电压足迹,包含了有关其解剖学、形态学和功能特性的大量信息。然而,由于EI的高维性质,对这些特性的分析很复杂。我们提出了一种基于优化的新算法,将EI分解为一种低维的、基于生物物理学的表示:对应于在体细胞、树突和轴突细胞区室中产生的尖峰波形的三个学习到的基波形的时间移位叠加。使用来自猕猴视网膜的大规模多电极记录对这种分解进行了评估。这种分解准确地定位了细胞的体细胞和树突区室。RGC的推断树突场正确地预测了它们视觉感受野的位置和形状。推断出的波形幅度和形状比以前的方法更准确地识别了四种主要的灵长类RGC类型(ON和OFF侏儒细胞和伞状细胞)。这些发现有助于仅基于RGC的电特征更准确地推断其类型及其原始光反应,对视力恢复技术具有潜在意义。