Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon 97239, and Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
J Neurosci. 2013 Oct 9;33(41):16045-59. doi: 10.1523/JNEUROSCI.1249-13.2013.
In the primate visual system, the ganglion cells of the magnocellular pathway underlie motion and flicker detection and are relatively transient, while the more sustained ganglion cells of the parvocellular pathway have comparatively lower temporal resolution, but encode higher spatial frequencies. Although it is presumed that functional differences in bipolar cells contribute to the tuning of the two pathways, the properties of the relevant bipolar cells have not yet been examined in detail. Here, by making patch-clamp recordings in acute slices of macaque retina, we show that the bipolar cells within the magnocellular pathway, but not the parvocellular pathway, exhibit voltage-gated sodium (NaV), T-type calcium (CaV), and hyperpolarization-activated, cyclic nucleotide-gated (HCN) currents, and can generate action potentials. Using immunohistochemistry in macaque and human retinae, we show that NaV1.1 is concentrated in an axon initial segment (AIS)-like region of magnocellular pathway bipolar cells, a specialization not seen in transient bipolar cells of other vertebrates. In contrast, CaV3.1 channels were localized to the somatodendritic compartment and proximal axon, but were excluded from the AIS, while HCN1 channels were concentrated in the axon terminal boutons. Simulations using a compartmental model reproduced physiological results and indicate that magnocellular pathway bipolar cells initiate spikes in the AIS. Finally, we demonstrate that NaV channels in bipolar cells augment excitatory input to parasol ganglion cells of the magnocellular pathway. Overall, the results demonstrate that selective expression of voltage-gated channels contributes to the establishment of parallel processing in the major visual pathways of the primate retina.
在灵长类动物视觉系统中，大细胞通路的神经节细胞是运动和闪烁检测的基础，相对来说是短暂的，而小细胞通路的持续时间更长的神经节细胞具有相对较低的时间分辨率，但编码更高的空间频率。尽管人们推测双极细胞的功能差异有助于两条通路的调谐，但相关双极细胞的特性尚未得到详细研究。在这里，我们通过在恒河猴视网膜急性切片上进行膜片钳记录，显示大细胞通路上的双极细胞表现出电压门控钠（NaV）、T 型钙（CaV）和超极化激活、环核苷酸门控（HCN）电流，并能产生动作电位。使用恒河猴和人视网膜的免疫组织化学染色，我们发现 NaV1.1 集中在大细胞通路上的双极细胞的轴突起始段（AIS）样区域，这是其他脊椎动物的瞬时双极细胞所没有的特化现象。相比之下，CaV3.1 通道位于胞体树突和近端轴突，但被排除在 AIS 之外，而 HCN1 通道则集中在轴突末梢的小球上。使用一个分室模型的模拟再现了生理结果，并表明大细胞通路上的双极细胞在 AIS 中引发尖峰。最后，我们证明双极细胞中的 NaV 通道增强了大细胞通路上的伞状神经节细胞的兴奋性输入。总的来说，这些结果表明，电压门控通道的选择性表达有助于建立灵长类动物视网膜主要视觉通路的并行处理。
