Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway
Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway
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DOI：
10.1523/jneurosci.1718-06.2006
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发表时间：
2006-11-15
影响因子：
5.3
通讯作者：
Copenhagen, David R.
中科院分区：
文献类型：
--
作者：
Renteria, Rene C.;Tian, Ning;Copenhagen, David R.
平行的ON和OFF通路将视觉信号从视网膜中的双极细胞传导到大脑中的更高中心。ON反应被认为是通过专门使用在视网膜ON双极细胞中表达的代谢型谷氨酸受体6（mGluR 6）而产生的。奇怪的是，我们发现在视网膜神经节细胞的mGluR 6-null小鼠的ON反应，但它们发生在长的潜伏期。长潜伏期ON反应不被代谢型谷氨酸或胆碱能受体拮抗剂阻断，也不通过激活感受野周围产生。我们表明，这些较长的延迟ON响应中启动的OFF途径。我们的研究结果揭示了一个以前未被认识到的内在属性的关闭视网膜通路，产生响应光的发病。在mGluR 6缺失小鼠中，在视觉皮层中观察到长潜伏期ON反应，表明它们可以可靠地传导到更高的视觉区域。在野生型（WT）小鼠中，APB（DL-2-氨基-4-膦酰基丁酸），一种mGluR 6激动剂，阻断了正常的短潜伏期ON反应，但揭示了较长潜伏期的反应。我们发现，这些潜在的混淆ON的OFF途径的反应，积极抑制野生型小鼠通过两个可分离的视网膜电路，激活了视网膜中的ON系统。因此，我们提出，ON通路到OFF通路的信号传导的主要功能是抑制这些不合时宜的，因此不适当的光诱发反应。
Parallel ON and OFF pathways conduct visual signals from bipolar cells in the retina to higher centers in the brain. ON responses are thought to originate by exclusive use of metabotropic glutamate receptor 6 (mGluR6) expressed in retinal ON bipolar cells. Paradoxically, we find ON responses in retinal ganglion cells of mGluR6-null mice, but they occur at long latency. The long-latency ON responses are not blocked by metabotropic glutamate or cholinergic receptor antagonists and are not produced by activation of receptive field surrounds. We show that these longer-latency ON responses are initiated in the OFF pathways. Our results expose a previously unrecognized intrinsic property of OFF retinal pathways that generates responses to light onset. In mGluR6-null mice, long-latency ON responses are observed in the visual cortex, indicating that they can be conducted reliably to higher visual areas. In wild-type (WT) mice, APB (DL-2-amino-4-phosphonobutyric acid), an mGluR6 agonist, blocks normal, short-latency ON responses but unmasks longer-latency ones. We find that these potentially confusing ON responses in the OFF pathway are actively suppressed in WT mice via two pharmacologically separable retinal circuits that are activated by the ON system in the retina. Consequently, we propose that a major function of the signaling of the ON pathway to the OFF pathway is suppression of these mistimed, and therefore inappropriate, light-evoked responses.