GABAA Receptors Containing the α2 Subunit Are Critical for Direction-Selective Inhibition in the Retina
GABAA Receptors Containing the α2 Subunit Are Critical for Direction-Selective Inhibition in the Retina
复制标题
DOI：
10.1371/journal.pone.0035109
复制
发表时间：
2012-04-10
期刊：
影响因子：
3.7
通讯作者：
Euler, Thomas
中科院分区：
文献类型：
--
作者：
Auferkorte, Olivia Nicola;Baden, Tom;Euler, Thomas
视网膜远不是一个简单的传感器，它积极参与处理视觉信号。这一过程最容易理解的一个方面是运动方向的检测。方向选择(DS)视网膜回路包括几种亚型的神经节细胞(GC)和抑制性中间神经元，如星爆无长突细胞(SACs)。最近的研究表明，DS环路中突触的排列令人惊讶地复杂，即在囊和DS神经节细胞之间。因此，为了充分了解视网膜DS的机制，需要对所有涉及的突触元素，特别是神经递质受体的性质和定位，有详细的了解。由于SACs对DSGCs的抑制是产生视网膜方向选择性的关键，我们在这里研究了介导这种相互作用的GABA受体的性质。我们发现在小鼠和兔视网膜的内丛状层，GABA(A)受体亚单位α2(GABA(A)Rα2)聚集在突触簇中，沿着重叠在囊上和囊外树突丛的两条带聚集在一起。在兔单独标记的囊的远端树突上，GABA(A)Rα2与细胞的输出结构--大多数精索排列在一起，并出现在位于IPL的ON和OFF部分的DSGC树突上。在GABA(A)Rα2基因敲除(KO)小鼠中，用双光子钙成像记录的视网膜GCs的光反应显示，与它们的野生型小鼠相比，DS反应显著受损。我们观察到，在ON和ON-OFF人群中，表现DS表型的细胞比例显著下降，这有力地支持了我们的解剖学发现，即含有α2的GABA(A)R对于介导视网膜DS抑制至关重要。据我们所知，我们的研究首次揭示了视网膜DS回路中特定受体亚单位的精确功能定位。
Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS) retinal circuits include several subtypes of ganglion cells (GCs) and inhibitory interneurons, such as starburst amacrine cells (SACs). Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL) of mouse and rabbit retina, GABA(A) receptor subunit alpha 2 (GABA(A)R alpha 2) aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABA(A)R alpha 2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABA(A)R alpha 2 knock-out (KO) mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that alpha 2-containing GABA(A)Rs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit.