Synaptic inputs to retinal ganglion cells that set the circadian clock
Synaptic inputs to retinal ganglion cells that set the circadian clock
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DOI：
10.1111/j.1460-9568.2006.04999.x
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发表时间：
2006-08-01
影响因子：
3.4
通讯作者：
Brown, R. Lane
中科院分区：
文献类型：
--
作者：
Perez-Leon, Jorge Alberto;Warren, Erin J.;Brown, R. Lane
含黑视素的视网膜神经节细胞（RGCs）投射到视交叉上核（SCN）并介导昼夜节律系统的光干扰。黑视素是一种新的基于视网膜的光色素，使这些细胞具有内在的光敏性（ip）。尽管黑视素的基因消融消除了内在的光反应，但它对昼夜节律光干扰的影响却微乎其微。只有当黑视素缺乏与传统的杆状和锥状光感受器失效的突变相结合时，这种和其他非视觉对光的反应才会消失，这表明含有黑视素的rgc也接受杆状和锥状驱动的突触输入。利用全细胞膜片钳记录，我们证明了光通过激活嗜离子性谷氨酸和γ -氨基丁酸（GABA）受体触发iprgc中的突触电流。在ipRGCs中可以清楚地观察到微型突触后电流（mPSCs），尽管它们的强度和频率低于非ip细胞。药理治疗表明，大多数iprgc接受兴奋性谷氨酸能输入，这些输入被DNQX和/或犬尿酸阻断，以及抑制性gaba能输入，被二叉碱阻断。其他ipRGCs几乎只接受谷氨酸能或gaba能输入。虽然对士的宁敏感的mPSCs在许多非iprgc中都很明显，表明甘氨酸能输入的存在，但我们在iprgc中没有看到士的宁敏感事件的证据。基于这些结果，很明显，scn投射的rgc可以通过内在的基于黑视素的信号级联和由经典的杆状和/或锥状光感受器驱动的突触通路对光做出反应。iprgc如何整合这些时间上不同的输入来产生介导昼夜光携带和其他非视觉对光反应的信号仍有待确定。
Melanopsin-containing retinal ganglion cells (RGCs) project to the suprachiasmatic nuclei (SCN) and mediate photoentrainment of the circadian system. Melanopsin is a novel retinal-based photopigment that renders these cells intrinsically photosensitive (ip). Although genetic ablation of melanopsin abolishes the intrinsic light response, it has a surprisingly minor effect on circadian photoentrainment. This and other non-visual responses to light are lost only when the melanopsin deficiency is coupled with mutations that disable classical rod and cone photoreceptors, suggesting that melanopsin-containing RGCs also receive rod- and cone-driven synaptic inputs. Using whole-cell patch-clamp recording, we demonstrate that light triggers synaptic currents in ipRGCs via activation of ionotropic glutamate and gamma-aminobutyric acid (GABA) receptors. Miniature postsynaptic currents (mPSCs) were clearly observed in ipRGCs, although they were less robust and were seen less frequently than those seen in non-ip cells. Pharmacological treatments revealed that the majority of ipRGCs receive excitatory glutamatergic inputs that were blocked by DNQX and/or kynurenic acid, as well as inhibitory GABAergic inputs that were blocked by bicuculline. Other ipRGCs received either glutamatergic or GABAergic inputs nearly exclusively. Although strychnine (Strych)-sensitive mPSCs were evident on many non-ipRGCs, indicating the presence of glycinergic inputs, we saw no evidence of Strych-sensitive events in ipRGCs. Based on these results, it is clear that SCN-projecting RGCs can respond to light both via an intrinsic melanopsin-based signaling cascade and via a synaptic pathway driven by classical rod and/or cone photoreceptors. It remains to be determined how the ipRGCs integrate these temporally distinct inputs to generate the signals that mediate circadian photoentrainment and other non-visual responses to light.