Kittila C A, Massey S C
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston 77030, USA.
J Neurophysiol. 1997 Feb;77(2):675-89. doi: 10.1152/jn.1997.77.2.675.
In this report we describe extracellular recordings made from ON and ON-OFF directionally selective (DS) ganglion cells in the rabbit retina during perfusion with agonists and antagonists to acetylcholine (ACh), glutamate, and gamma-aminobutyric acid (GABA). Nicotinic ACh agonists strongly excited DS ganglion cell in a dose-dependent manner. Dose-response curves showed a wide range of potencies, with (+/-)-exo-2-(6-chloro-3pyridinyl)-7-azabicyclo[2.2.1] heptane dihydrochloride (epibatidine) > > > nicotine > 1,1-dimethyl-4-phenylpiperazinium iodide = carbachol. In addition, the mixed cholinergic agonist carbachol produced a small excitation, mediated by muscarinic receptors, that could be blocked by atropine. The specific nicotinic antagonists hexamethonium bromide (100 microM), dihydro-beta-erythroidine (50 microM), mecamylamine (50 microM), and tubocurarine (50 microM) blocked the responses to nicotinic agonists. In addition, nicotinic antagonists reduced the light-driven input to DS ganglion cells by approximately 50%. However, attenuated responses were still DS. We deduce that cholinergic input is not required for directional selectivity. These experiments reveal the importance of bipolar cell input mediated by glutamate. N-methyl-D-aspartic acid (NMDA) excited DS ganglion cells, but NMDA antagonists did not abolish directional selectivity. However, a combined cholinergic and NMDA blockade reduced the responses of DS ganglion cells by > 90%. This indicates that most of the noncholinergic excitatory input appears to be mediated by NMDA receptors, with a small residual made up by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptors. Responses to AMPA and KA were highly variable and often evoked a mixture of excitation and inhibition due to the release of ACh and GABA. Under cholinergic blockade AMPA/KA elicited a strong GABA-mediated inhibition in DS ganglion cells. AMPA/KA antagonists, such as 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F)quinoxaline dione and GYKI-53655, promoted null responses and abolished directional selectivity due to the blockade of GABA release. We conclude that GABA release, mediated by non-NMDA glutamate receptors, is an essential part of the mechanism of directional selectivity. The source of the GABA is unknown, but may arise from starburst amacrine cells.
在本报告中，我们描述了在向兔视网膜灌注乙酰胆碱（ACh）、谷氨酸和γ-氨基丁酸（GABA）的激动剂和拮抗剂期间，从兔视网膜中的ON和ON-OFF方向选择性（DS）神经节细胞进行的细胞外记录。烟碱型ACh激动剂以剂量依赖性方式强烈兴奋DS神经节细胞。剂量反应曲线显示出广泛的效价范围，（±）-外型-2-（6-氯-3-吡啶基）-7-氮杂双环[2.2.1]庚烷二盐酸盐（埃博霉素）>>>尼古丁>1,1-二甲基-4-苯基哌嗪碘化物=卡巴胆碱。此外，混合胆碱能激动剂卡巴胆碱产生了由毒蕈碱受体介导的小兴奋，可被阿托品阻断。特异性烟碱拮抗剂溴化六甲铵（100μM）、二氢-β-刺桐碱（50μM）、美加明（50μM）和筒箭毒碱（50μM）阻断了对烟碱激动剂的反应。此外，烟碱拮抗剂使DS神经节细胞的光驱动输入减少了约50%。然而，减弱的反应仍然是方向选择性的。我们推断方向选择性不需要胆碱能输入。这些实验揭示了由谷氨酸介导的双极细胞输入的重要性。N-甲基-D-天冬氨酸（NMDA）兴奋DS神经节细胞，但NMDA拮抗剂并未消除方向选择性。然而，胆碱能和NMDA联合阻断使DS神经节细胞的反应减少了>90%。这表明大部分非胆碱能兴奋性输入似乎由NMDA受体介导，一小部分残余由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/海人藻酸（KA）受体组成。对AMPA和KA的反应高度可变，并且由于ACh和GABA的释放常常引起兴奋和抑制的混合。在胆碱能阻断下，AMPA/KA在DS神经节细胞中引起强烈的GABA介导的抑制。AMPA/KA拮抗剂，如2,3-二羟基-6-硝基-7-氨磺酰基苯并（F）喹喔啉二酮和GYKI-53655，由于GABA释放的阻断促进了无反应并消除了方向选择性。我们得出结论，由非NMDA谷氨酸受体介导的GABA释放是方向选择性机制的重要组成部分。GABA的来源尚不清楚，但可能来自星爆无长突细胞。
