PDF(Pubmed)
Abstract：
Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with retinitis pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses or how inhibition might be altered during degeneration. Using whole-cell voltage-clamp recordings during subretinal electrical stimulation in the rd10 and wild-type (wt) retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that the inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre- and postsynaptic inhibition in the OFF pathway arises from glycinergic amacrine cells, and the stimulation of the ON pathway contributes to inhibitory inputs to the RGC. We also show that this presynaptic inhibition in the OFF pathway is greater in the rd10 retina, compared with that in the wt retina.
摘要：
视网膜假体是恢复视网膜色素变性和年龄相关性黄斑变性患者视力丧失的主要治疗策略之一。许多工作已经描述了响应电刺激的视网膜神经节细胞（RGC）的尖峰模式，但较少的工作是检查由电刺激激活的潜在视网膜电路来驱动这些反应。令人惊讶的是,对抑制在产生电反应中的作用知之甚少，或者在变性过程中抑制可能如何改变。在rd10和wt视网膜的视网膜下电刺激期间使用全细胞电压钳记录，我们发现电诱发突触输入在ON和OFFRGC群体之间有所不同，ON细胞主要接受激发，OFF细胞主要接受抑制和很少的激发。我们发现OFF双极细胞的抑制限制了OFFRGC的兴奋，并且OFF通路中的大部分突触前和突触后抑制都来自于甘氨酸能的无能细胞，和ON途径的刺激有助于RGC的抑制性输入。我们还表明，这种在OFF通路中的突触前抑制在rd10视网膜中更大，与野生型（wt）视网膜相比。意义陈述电路处理的变化可能对色素性视网膜炎患者的视力恢复产生有害影响。先前的研究集中在前馈兴奋驱动，而不是包括正常视网膜功能的兴奋和抑制之间的相互作用。这项研究表明，视网膜神经节细胞在三个与其解剖结构相对应的广泛功能组中对电刺激作出反应。我们表明，虽然退化和wt视网膜显示相同的三组，变性视网膜的OFF通路突触前抑制量增加，限制了它们对OFF神经节细胞的兴奋性输出。
