National Vision Research Institute, Australian College of Optometry, Australia. Department of Biomedical Engineering, The University of Melbourne, Australia.
J Neural Eng. 2018 Aug;15(4):046012. doi: 10.1088/1741-2552/aabb7d. Epub 2018 Apr 4.
The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina.
We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model.
We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n = 20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself.
An upper threshold observed in the soma does not prevent spike conductance in the axon.
电刺激视网膜神经节细胞(RGC)中存在上阈值,这是因为它与视觉假体设备的发展有关,这些设备旨在为盲人恢复部分视力。上阈值被定义为刺激水平,超过该水平,电刺激视网膜中就无法引出动作电位(直接尖峰)。
我们收集并分析了大鼠 RGC 在不同幅度和脉冲持续时间的体外双相(阳极-阴极)脉冲刺激下的反应记录。使用多室模型也对这些反应进行了模拟。
我们在所有记录的细胞(n=20/21)中确定了对刺激的单个细胞变异性和上阈值现象。我们发现,相对于刺激幅度的尖峰反应潜伏期具有特征性的 U 形。在计算机模拟中,我们发现仅在胞体中观察到上阈值现象。对于所有测试的双相脉冲持续时间、电极位置和高于下阈值的脉冲幅度,在远端轴突中观察到传播动作电位。对于高于胞体上阈值的幅度,轴突动作电位沿轴突向胞体方向逆行传播,但胞体的低水平超极化阻止了胞体本身产生动作电位。
在胞体中观察到的上阈值不会阻止轴突中的尖峰传导。