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首页> 外文期刊>Investigative ophthalmology & visual science >Dopamine acts presynaptically to suppress GABA-ergic mediated lateral inhibition to rod bipolar cells in mouse retina.
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Dopamine acts presynaptically to suppress GABA-ergic mediated lateral inhibition to rod bipolar cells in mouse retina.

机译：多巴胺先天性地抑制小鼠视网膜中杆状双极细胞的GABA能介导的侧向抑制。

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Purpose : Dopamine (DA) is known to facilitate the shift from rod (high sensitivity, low acuity) to cone (low sensitivity, high acuity) signaling during adaption in the mammalian retina. The precise effects of dopamine on network adaptation in the inner retina are unclear. During light adaptation, ?3-amino-butyric acid (GABA) mediated lateral inhibition onto RBCs decreases. Does dopamine modulate (GABA) receptor responsiveness or does it modulate GABA release? Here we describe how dopamine suppresses the release of GABA from amacrine cells (ACs) onto rod bipolar cell (RBC) terminals. Methods : Mouse RBCs were recorded using whole cell voltage clamp techniques in (200 or 400 micron) thick retina slices. RBCs were morphologically identified by dye. GABA receptor activity was directly measured by puffing GABA onto RBC terminals. GABAergic inhibitory post-synaptic currents (IPSCs) were evoked by activation of ACs with either AMPA puffs or light. All experiments that did not involve light-evoked responses were conducted in the light when dopamine is naturally saturating. Results : We show that dopamine has no direct effect on GABARs on RBC terminals. We blocked D1 receptors with SCH-23390 in WT slices and found no effect on GABA-puff mediated currents. Similarly, GABA responses were also unaffected by application of the dopamine agonist, ADTN, in slices prepared from retina specific tyrosine hydroxylase (Thy1) conditional knockout mice, which do not produce retinal dopamine. However, antagonism of D1 receptors in WT slices significantly increased the level of lateral inhibition evoked by AMPA in the IPL. Further, ADTN suppresses light-evoked IPSCs in dark-adapted slices. Thus, dopamine modulation altered evoked GABA-IPSCs, without affecting GABAR responsiveness. Conclusions : Our findings suggest that dopamine suppresses GABA-mediated inhibition in RBC terminals by modulating GABA release from ACs. We previously showed that RBC GABAR mediated inhibition was suppressed by increasing light illumination. Our data provide a mechanistic framework for this finding and suggest that increasing dopamine levels suppress GABAR inhibition. Our results offer new insights into the molecular mechanisms of network adaptation in the mammalian retina. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
机译：目的：已知多巴胺（DA）有助于在哺乳动物视网膜适应过程中从视杆（高敏感度，低敏度）信号转为视锥（低敏感度，高敏度）信号。多巴胺对视网膜内部网络适应的确切作用尚不清楚。在光适应过程中，β3-氨基丁酸（GABA）介导的对RBC的侧向抑制作用降低。多巴胺会调节（GABA）受体反应性还是会调节GABA释放？在这里，我们描述了多巴胺如何抑制GABA从无长突细胞（AC）到杆状双极细胞（RBC）末端的释放。方法：使用全细胞电压钳技术在200或400微米厚的视网膜切片中记录小鼠RBC。红细胞通过染料在形态上鉴定。通过将GABA吹入RBC末端直接测量GABA受体的活性。 GABA能抑制突触后电流（IPSC）是通过用AMPA吹气或光激活AC引起的。当多巴胺自然饱和时，所有不涉及光诱发反应的实验均在光照下进行。结果：我们表明，多巴胺对RBC末端的GABAR没有直接影响。我们在WT切片中用SCH-23390阻断了D1受体，但未发现对GABA抽吸介导的电流有影响。同样，在由视网膜特异性酪氨酸羟化酶（Thy1）条件性基因敲除小鼠制备的切片中，多巴胺激动剂ADTN的应用也不会影响GABA反应，而这种小鼠不会产生视网膜多巴胺。但是，WT切片中D1受体的拮抗作用显着增加了IPL中AMPA引起的侧向抑制水平。此外，ADTN可以在暗适应的切片中抑制光诱发的IPSC。因此，多巴胺调节改变了诱发的GABA-IPSC，而没有影响GABAR的响应性。结论：我们的发现表明，多巴胺可通过调节AC中GABA的释放来抑制RBC末端中GABA介导的抑制。我们以前表明，RBC GABAR介导的抑制作用通过增加光照来抑制。我们的数据为这一发现提供了一个机制框架，并表明增加多巴胺水平可以抑制GABAR抑制作用。我们的结果为哺乳动物视网膜网络适应的分子机制提供了新的见解。这是提交给2016年5月1-5日在华盛顿州西雅图市举行的2016 ARVO年会的摘要。

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