The mechanism by which electric stimulation activates retinal neurons

在过去的十年中，几种基于CNS的神经修复体取得了显着的成就， 临床结果。例如，脑深部电刺激（DBS）现在通常用于治疗 帕金森震颤和人工耳蜗刺激听觉神经恢复高 听力水平的变化。然而，并非所有设备都实现了相同的 成功的水平。例如，视网膜假体不能可靠地引起复杂的（或甚至是复杂的）视网膜损伤。 简单的）空间感知，即使单个电极可以一致地引起焦点 光幻视（Phosphenes）。即使是更成功的应用程序有时也会 不一致，并产生了不必要的副作用。为了改善结果， 与视网膜（和其他神经）修复相关，我们正在研究基本的 电刺激和目标神经元之间的相互作用， 电生理学、解剖学和计算建模。在视网膜神经元中，我们发现 响应于电刺激的最低阈值出现在刺激 电极位于轴突的近端部分上（靠近索马）。这一地区 与电压门控钠通道的密集带精确对齐 免疫化学鉴定。不同类型的视网膜神经元有不同的带 （长度和位置）以及不同的绝对（最低）阈值。这意味着 波段差异有助于阈值差异，我们建议调查 发生这种情况的细节。很可能，该带也是尖峰出现的部位。 开始，但这还没有得到证实;在这里，我们提出了几个实验， 确定该带是否实际上是该网站。了解峰电位起始部位 使我们能够系统地研究如何改变所施加的电场（由 刺激脉冲）改变神经反应。我们的初步数据显示， 类似于轴突的刺激，感应电压的二阶空间导数 沿该带沿着的轮廓是脉冲功效的良好预测器。在时间域中，我们 我想确定哪种刺激模式对激活不同的元素最有效 在神经元内。我们还在探索是否有特定的类或子类 神经元优先对不同的刺激频率作出反应。我们希望通过 了解反应机制的基本要素，包括 不同类型的神经元之间的反应差异，我们可以开发更有效的 刺激方法，这将导致更好的临床结果。

In the past decade, several CNS-based neural prosthetics have achieved remarkable clinical outcomes. For example, deep brain stimulation (DBS) is now routinely used to treat Parkinsonian tremors and cochlear prosthetics stimulate the auditory nerve to restore high levels of hearing to the profoundly deaf. However, not all devices have achieved the same level of success. For example, retinal prosthetics do not reliably elicit complex (or even simple) spatial percepts even though individual electrodes can consistently elicit focal percepts (phosphenes). Even the more successful applications can sometimes be inconsistent and have created unwanted side effects. To improve the outcomes associated with retinal (and other neural) prosthetics, we are studying the fundamental interactions between electric stimulation and targeted neurons using a combination of electrophysiology, anatomy and computational modeling. In retinal neurons, we found that the lowest thresholds in response to electric stimulation occur when the stimulating electrode is positioned over the proximal portion of the axon (near the soma). This region of low threshold is precisely aligned with a dense band of voltage-gated sodium channels identified immunochemically. Different types of retinal neurons have different bands (lengths and locations) as well as different absolute (lowest) thresholds. This implies that band differences contribute to threshold differences and we propose to investigate the details by which this occurs. It is likely that the band is also the site in which spikes are initiated but this has not yet been confirmed; here, we propose several experiments to determine whether the band is in fact the site. Knowledge of the site of spike initiation enables us to systematically study how changes to the applied electric field (arising from the stimulus pulse) alter the neural response. Our preliminary data suggests that analogous to stimulation of axons, the second spatial derivative of the induced voltage profile along the band is a good predictor of pulse efficacy. In the temporal domain, we want to determine which stimulus profile is most effective for activating different elements within the neuron. We are also exploring whether specific classes or sub-classes of neurons respond preferentially to different stimulus frequencies. Our hope is that by understanding the basic elements of the response mechanism, including the cause of response differences between different types of neurons, we can develop more effective stimulation methods that will lead to better clinical outcomes.