The absence of Complexin 3 and Complexin 4 differentially impacts the ON and OFF pathways in mouse retina
The absence of Complexin 3 and Complexin 4 differentially impacts the ON and OFF pathways in mouse retina
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DOI：
10.1111/j.1460-9568.2012.08149.x
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发表时间：
2012-08-01
影响因子：
3.4
通讯作者：
Ammermueller, Josef
中科院分区：
文献类型：
--
作者：
Landgraf, Immanuel;Muehlhans, Johanna;Ammermueller, Josef
复合蛋白（Cplxs）调节突触囊泡融合的速度和Ca 2+敏感性。已经表明，所有四种已知的Cplx都存在于小鼠视网膜突触、常规无长突细胞突触（Cplx 1至Cplx 3）以及光感受器和双极细胞带状突触（Cplx 3和Cplx 4）[K. Reim（2005）J. Cell Biol.，169，669 - 680]。在Cplx 3/Cplx 4双基因敲除（DKO）小鼠中的视网膜电图记录显示外丛状层中的干扰传递，以及内丛状层中的可能变化[K. Reim（2009）J. Cell Sci.，122，13521361]。在本研究中，我们研究了Cplx 3和Cplx 4的缺乏对神经节细胞反应的影响。我们报告说，缺乏Cplx 3和Cplx 4差异影响ON和OFF途径。在明视条件下，视锥细胞OFF途径中的反应在很大程度上不受影响，而视锥细胞ON途径中的反应在Cplx 3/Cplx 4 DKO小鼠中减弱。在暗视条件下，在Cplx 3/Cplx 4 DKO小鼠中，ON和OFF响应率均降低，并且高灵敏度OFF响应缺失。新的免疫细胞化学结果证实了电生理结果。我们现在表明，杆小球只包含Cplx 4。然而，Cplx 3和Cplx 4两者共定位于锥椎弓根中。在内丛状层中，Cplx 3存在于杆双极细胞末端和无长突细胞突起中。最重要的是，Cplx 3位于AII无长突细胞的小叶附属物中，这是从初级视杆通路到内网状层中的OFF通路的信号传递的位点。
Complexins (Cplxs) regulate the speed and Ca2+-sensitivity of synaptic vesicle fusion. It has been shown that all four known Cplxs are present at mouse retinal synapses at conventional amacrine cell synapses (Cplx 1 to Cplx 3) and at photoreceptor and bipolar cell ribbon synapses (Cplx 3 and Cplx 4) [K. Reim (2005)J. Cell Biol.,169, 669-680]. Electroretinographic recordings in Cplx 3/Cplx 4 double-knockout (DKO) mice showed perturbed transmission in the outer plexiform layer, and possible changes in the inner plexiform layer [K. Reim (2009)J. Cell Sci.,122, 13521361]. In the present study, we examined the effects of the absence of Cplx 3 and Cplx 4 on ganglion cell responses. We report that the lack of Cplx 3 and Cplx 4 differentially impacts the ON and OFF pathways. Under photopic conditions, the responses in the cone OFF pathway are largely unaffected, whereas the responses in the cone ON pathway are diminished in Cplx 3/Cplx 4 DKO mice. Under scotopic conditions, both ON and OFF response rates are reduced and high-sensitivity OFF responses are missing in Cplx 3/Cplx 4 DKO mice. The electrophysiological findings are corroborated by new immunocytochemical findings. We now show that rod spherules contain only Cplx 4. However, both Cplx 3 and Cplx 4 co-localize in cone pedicles. In the inner plexiform layer, Cplx 3 is present in rod bipolar cell terminals and in amacrine cell processes. Most importantly, Cplx 3 is localized in the lobular appendages of AII amacrine cells, the sites of signal transmission from the primary rod pathway into the OFF pathway in the inner plexiform layer.