Genetic control of circuit function:: Vsx1 and Irx5 transcription factors regulate contrast adaptation in the mouse retina
Genetic control of circuit function:: Vsx1 and Irx5 transcription factors regulate contrast adaptation in the mouse retina
复制标题
DOI：
10.1523/jneurosci.4784-07.2008
复制
发表时间：
2008-03-05
影响因子：
5.3
通讯作者：
Wong, Rachel O. L.
中科院分区：
文献类型：
--
作者：
Kerschensteiner, Daniel;Liu, Haiquan;Wong, Rachel O. L.
转录程序指导发育中的神经系统中神经细胞类型的规范。然而，尚不清楚这些程序是否也控制成熟时神经回路功能的特定方面。在哺乳动物视网膜中，Vsx1 和 Irx5 转录因子存在于将信号从感光器传递到神经节细胞的双极中间神经元子集中。与去极化 ON 双极细胞相比，Vsx1 和 Irx5 在超极化 OFF 中的偏向表达表明这些转录因子可能选择性地调节 OFF 电路中的信号处理。为了验证这一假设，我们培育了同时缺乏 Vsx1 和 Irx5 的小鼠。这些小鼠的双极细胞形态正常，但一些 OFF（而非 ON）双极细胞中细胞特异性标记物的表达减少或缺失。为了评估 Vsx1(-/-) Irx5(-/-) 视网膜的视觉功能，我们记录了视网膜神经节细胞 (RGC) 群的光反应。我们首先确定了对照小鼠的功能性 RGC 类型，并使用简单的线性非线性模型描述了它们的响应特性和对时间对比度的适应。我们发现与对照视网膜相比，Vsx1(-/-) Irx5(-/-) 小鼠的 RGC 时空感受野没有变化。相比之下，Vsx1(-/-) Irx5(-/-) 视网膜中关闭而非开启的 RGC 的响应阈值、增益和范围以细胞类型特异性方式降低。最后，我们发现双突变体中的 OFF RGC 适应时间对比度的能力大大降低，这表明 Vsx1 和 Irx5 控制哺乳动物视网膜回路中视觉功能的特定方面。
Transcriptional programs guide the specification of neural cell types in the developing nervous system. However, it is unclear whether such programs also control specific aspects of neural circuit function at maturity. In the mammalian retina, Vsx1 and Irx5 transcription factors are present in a subset of bipolar interneurons that convey signals from photoreceptors to ganglion cells. The biased expression of Vsx1 and Irx5 in hyperpolarizing OFF compared with depolarizing ON bipolar cells suggests that these transcription factors may selectively regulate signal processing in OFF circuits. To test this hypothesis, we generated mice lacking both Vsx1 and Irx5. Bipolar cells in these mice were morphologically normal, but the expression of cell-specific markers in some OFF but not ON bipolar cells was reduced or absent. To assess visual function in Vsx1(-/-) Irx5(-/-) retinas, we recorded light responses from ensembles of retinal ganglion cells (RGCs). We first identified functional RGC types in control mice and describe their response properties and adaptation to temporal contrast using a simple linear-nonlinear model. We found that space-time receptive fields of RGCs are unchanged in Vsx1(-/-) Irx5(-/-) mice compared with control retinas. In contrast, response threshold, gain, and range were lowered in a cell-type-specific manner in OFF but not ON RGCs in Vsx1(-/-) Irx5(-/-) retinas. Finally, we discovered that the ability to adapt to temporal contrast is greatly reduced in OFF RGCs in the double mutant, suggesting that Vsx1 and Irx5 control specific aspects of visual function in circuits of the mammalian retina.