Synaptic Plasticity of Retinal Neurones

本文研究了鲤科鱼类视网膜中视锥细胞到H1型水平细胞（H1 HCs）的突触传递。突触长期以来被认为是谷氨酸驱动的非NMDA通道类型。从几年前开始，我们的日本-英国小组就一直在修正关于短波长信号的突触传递的概念;我们的一组证据表明，蓝色和/或绿色视锥形成的突触是一种电导降低和极性反转型的突触，伴有APB（2-氨基-4-膦酰基丁酸酯）作为激动剂。关于APB突触仍有两个主要课题有待探索，即，在视觉功能中的作用和潜在的分子机制。今年，我们的国际团队在这方面取得了很大进展。首先，通过测量输入电阻发现，暗适应可阻断短波长突触传递，且阻断作用的部位在突触后。因此，很明显，突触的可塑性是刺激波长和视网膜光暗适应的函数。此外，我们的另一系列实验表明，与这些属性的突触subserves波长和适应依赖的控制H1毛细胞的感受野大小。为了定量地解释这种效应，我们目前正在开发一个非线性版本的电缆理论模型的H1 HC合胞体中的膜电阻是可变的，而不是恒定的间隙连接resistance. To阐明突触的分子机制的问题，我们进行了一定的实验，涉及细胞内注射cGMP和灌注硝普钠。结果表明，突触机制是代谢型的，在从APB受体到通道门控的过程中涉及G蛋白 *PDE*cGMP和/或Ca^2+* NOS*NO*GC*CGM。

This research is concerned with synaptic transmission from cone photoreceptors to H1 type horizontal cells (H1 HCs) in the cyprinid fish retina. The synapse had long been thought to be of the glutamate-driven non-NMDA channel type. Since several years ago, our Japan-UK group has been revising this notion with respect to the synaptic transmission for short-wavelength signals ; our set of evidence shows that the synapse made by blue and/or green cones is of a conductance-decreasing and polarity-reversing type with APB (2-amino-4-phosphonobutyrate) as an agonist.There remain two major subjects to be explored about the APB synapse, namely, the role in visual function and the underlying molecular mechanisms. This year, our international team was able to make considerable progress to this end. First, it was found by input-resistance measurement that the short-wavelength synaptic transmission is blocked reversely by dark adaptation, and that the site of the blocking action is postsynaptic. It has become evident, therefore, that the synapse operates with plasticity as a function of stimulus wavelength and light/dark retinal adaptation. Furthermore, another series of our experiments showed that the synapse with these properties subserves wavelength- and adaptation-dependent control on the receptive field size of H1 HCs. To account for this effect quantitatively, we are currently developing a nonlinear version of the cable-theory model of the H1 HC syncitium in which the membrane resistance is variable as opposed to the constant gap-junctional resistance.In order to elucidate the molecular mechanisms underlying the synapse in question, we carried out certain experiments involving intracellular injection of cGMP and superfusion with nitroprusside. The results so far indicate that the synaptic mechanism is metabotropic, involving G-protein*PDE*cGMP, and/or Ca^<2+>* NOS*NO*GC*cGM in the course from APB receptor to the channel gating.