Dagar Sushma, Nagar Saumya, Goel Manvi, Cherukuri Pitchaiah, Dhingra Narender K
National Brain Research Centre, Manesar (Gurgaon) Haryana, India.
PLoS One. 2014 Mar 4;9(3):e90250. doi: 10.1371/journal.pone.0090250. eCollection 2014.
Deafferentation is known to cause significant changes in the postsynaptic neurons in the central nervous system. Loss of photoreceptors, for instance, results in remarkable morphological and physiological changes in bipolar cells and horizontal cells. Retinal ganglion cells (RGCs), which send visual information to the brain, are relatively preserved, but show aberrant firing patterns, including spontaneous bursts of spikes in the absence of photoreceptors. To understand how loss of photoreceptors affects the circuitry presynaptic to the ganglion cells, we measured specific synaptic proteins in two mouse models of retinal degeneration. We found that despite the nearly total loss of photoreceptors, the synaptophysin protein and mRNA levels in retina were largely unaltered. Interestingly, the levels of synaptophysin in the inner plexiform layer (IPL) were higher, implying that photoreceptor loss results in increased synaptophysin in bipolar and/or amacrine cells. The levels of SV2B, a synaptic protein expressed by photoreceptors and bipolar cells, were reduced in whole retina, but increased in the IPL of rd1 mouse. Similarly, the levels of syntaxin-I and synapsin-I, synaptic proteins expressed selectively by amacrine cells, were higher after loss of photoreceptors. The upregulation of syntaxin-I was evident as early as one day after the onset of photoreceptor loss, suggesting that it did not require any massive or structural remodeling, and therefore is possibly reversible. Together, these data show that loss of photoreceptors results in increased synaptic protein levels in bipolar and amacrine cells. Combined with previous reports of increased excitatory and inhibitory synaptic currents in RGCs, these results provide clues to understand the mechanism underlying the aberrant spiking in RGCs.
已知去传入作用会导致中枢神经系统中突触后神经元发生显著变化。例如，光感受器的丧失会导致双极细胞和水平细胞出现明显的形态和生理变化。将视觉信息传递至大脑的视网膜神经节细胞（RGCs）相对保留，但会表现出异常的放电模式，包括在无光感受器的情况下出现自发的尖峰爆发。为了了解光感受器的丧失如何影响神经节细胞突触前的神经回路，我们在两种视网膜变性小鼠模型中测量了特定的突触蛋白。我们发现，尽管光感受器几乎完全丧失，但视网膜中突触素蛋白和mRNA水平基本未改变。有趣的是，内网状层（IPL）中突触素的水平更高，这意味着光感受器丧失会导致双极细胞和/或无长突细胞中突触素增加。感光细胞和双极细胞表达的突触蛋白SV2B在整个视网膜中的水平降低，但在rd1小鼠的IPL中升高。同样，无长突细胞选择性表达的突触蛋白 syntaxin-I 和突触蛋白-I 在光感受器丧失后的水平更高。 syntaxin-I 的上调早在光感受器丧失开始后的一天就很明显，这表明它不需要任何大规模或结构性重塑，因此可能是可逆的。总之，这些数据表明光感受器的丧失会导致双极细胞和无长突细胞中突触蛋白水平升高。结合之前关于RGCs中兴奋性和抑制性突触电流增加的报道，这些结果为理解RGCs异常放电的潜在机制提供了线索。
