Yu Wan-Qing, Grzywacz Norberto M, Lee Eun-Jin, Field Greg D
Neuroscience Graduate Program, University of Southern California, Los Angeles, California.
Department of Biomedical Engineering, University of Southern California, Los Angeles, California.
J Neurophysiol. 2017 Jul 1;118(1):434-454. doi: 10.1152/jn.00826.2016. Epub 2017 Apr 19.
We have determined the impact of rod death and cone reorganization on the spatiotemporal receptive fields (RFs) and spontaneous activity of distinct retinal ganglion cell (RGC) types. We compared RGC function between healthy and retinitis pigmentosa (RP) model rats (S334ter-3) at a time when nearly all rods were lost but cones remained. This allowed us to determine the impact of rod death on cone-mediated visual signaling, a relevant time point because the diagnosis of RP frequently occurs when patients are nightblind but daytime vision persists. Following rod death, functionally distinct RGC types persisted; this indicates that parallel processing of visual input remained largely intact. However, some properties of cone-mediated responses were altered ubiquitously across RGC types, such as prolonged temporal integration and reduced spatial RF area. Other properties changed in a cell type-specific manner, such as temporal RF shape (dynamics), spontaneous activity, and direction selectivity. These observations identify the extent of functional remodeling in the retina following rod death but before cone loss. They also indicate new potential challenges to restoring normal vision by replacing lost rod photoreceptors. This study provides novel and therapeutically relevant insights to retinal function following rod death but before cone death. To determine changes in retinal output, we used a large-scale multielectrode array to simultaneously record from hundreds of retinal ganglion cells (RGCs). These recordings of large-scale neural activity revealed that following the death of all rods, functionally distinct RGCs remain. However, the receptive field properties and spontaneous activity of these RGCs are altered in a cell type-specific manner.
我们已经确定了视杆细胞死亡和视锥细胞重组对视锥细胞介导的视觉信号传导的影响,这是一个相关的时间点,因为视网膜色素变性(RP)患者的诊断通常发生在患者出现夜盲但白天视力仍正常的时候。视杆细胞死亡后,功能不同的视网膜神经节细胞(RGC)类型依然存在;这表明视觉输入的并行处理在很大程度上保持完整。然而,视锥细胞介导的反应的一些特性在所有RGC类型中普遍发生了改变,例如时间整合延长和空间感受野面积减小。其他特性则以细胞类型特异性的方式发生变化,例如时间感受野形状(动态)、自发活动和方向选择性。这些观察结果确定了视杆细胞死亡后但视锥细胞丧失前视网膜功能重塑的程度。它们还表明,通过替换丢失的视杆光感受器来恢复正常视力面临着新的潜在挑战。这项研究为视杆细胞死亡后但视锥细胞死亡前的视网膜功能提供了新的、与治疗相关的见解。为了确定视网膜输出的变化,我们使用大规模多电极阵列同时记录数百个视网膜神经节细胞(RGC)的活动。这些大规模神经活动记录显示,在所有视杆细胞死亡后,功能不同的RGC依然存在。然而,这些RGC的感受野特性和自发活动以细胞类型特异性的方式发生了改变。
我们已经确定了视杆细胞死亡和视锥细胞重组对不同视网膜神经节细胞(RGC)类型的时空感受野(RFs)和自发活动的影响。我们比较了健康大鼠和视网膜色素变性(RP)模型大鼠(S334ter-3)在几乎所有视杆细胞丧失但视锥细胞仍保留时的RGC功能。这使我们能够确定视杆细胞死亡对视锥细胞介导的视觉信号的影响,这是一个相关的时间点,因为RP的诊断通常发生在患者夜盲但白天视力持续存在的时候。视杆细胞死亡后,功能不同的RGC类型持续存在;这表明视觉输入的并行处理在很大程度上保持完整。然而,视锥细胞介导的反应的一些特性在所有RGC类型中普遍发生了改变,例如时间整合延长和空间RF面积减小。其他特性则以细胞类型特异性的方式发生变化,例如时间RF形状(动态)、自发活动和方向选择性。这些观察结果确定了视杆细胞死亡后但视锥细胞丧失前视网膜功能重塑的程度。它们还表明,通过替换丢失的视杆光感受器来恢复正常视力面临着新的潜在挑战。这项研究为视杆细胞死亡后但视锥细胞死亡前的视网膜功能提供了新且与治疗相关的见解。为了确定视网膜输出的变化,我们使用大规模多电极阵列同时记录数百个视网膜神经节细胞(RGCs)。这些大规模神经活动记录显示,在所有视杆细胞死亡后,功能不同的RGCs依然存在。然而,这些RGCs的感受野特性和自发活动以细胞类型特异性的方式发生了改变。