Zucker Charles L, Nilson James E, Ehinger Berndt, Grzywacz Norberto M
Department Anatomy and Neurobiology, Boston University School of Medicine, 715 Albany Street, Massachusetts 02118, USA.
J Comp Neurol. 2005 Dec 19;493(3):448-59. doi: 10.1002/cne.20766.
Although many effects of gamma-aminobutyric acid (GABA) on retinal function have been attributed to GABA(A) and GABA(C) receptors, specific retinal functions have also been shown to be mediated by GABA(B) receptors, including facilitation of light-evoked acetylcholine release from the rabbit retina (Neal and Cunningham [1995] J. Physiol. 482:363-372). To explain the results of a rich set of experiments, Neal and Cunningham proposed a model for this facilitation. In this model, GABA(B) receptor-mediated inhibition of glycinergic cells would reduce their own inhibition of cholinergic cells. In turn, muscarinic input from the latter to the glycinergic cells would complete a negative-feedback circuitry. In this study, we have used immunohistochemical techniques to test elements of this model. We report that glycinergic amacrine cells are GABA(B) receptor negative. In contrast, our data reveal the localization of GABA(B) receptors on cholinergic/GABAergic starburst amacrine cells. High-resolution localization of GABA(B) receptors on starburst amacrine cells shows that they are discretely localized to a limited population of its varicosities, the majority of likely synaptic-release sites being devoid of detectable levels of GABA(B) receptors. Finally, we identify a glycinergic cell that is a potential muscarinic receptor-bearing target of GABA(B)-modulated acetylcholine release. This target is the DAPI-3 cell. We propose, based on these data, a modification of the Neal and Cunningham model in which GABA(B) receptors are on starburst, not glycinergic amacrine cells.
尽管γ-氨基丁酸(GABA)对视网膜功能的许多作用都归因于GABA(A)和GABA(C)受体,但特定的视网膜功能也已被证明是由GABA(B)受体介导的,包括促进兔视网膜中光诱发的乙酰胆碱释放(Neal和Cunningham [1995]《生理学杂志》482:363 - 372)。为了解释一系列丰富实验的结果,Neal和Cunningham提出了一个关于这种促进作用的模型。在这个模型中,GABA(B)受体介导的对甘氨酸能细胞的抑制会减少它们自身对胆碱能细胞的抑制。反过来,后者对甘氨酸能细胞的毒蕈碱输入将完成一个负反馈回路。在本研究中,我们使用免疫组织化学技术来测试该模型的各个要素。我们报告甘氨酸能无长突细胞为GABA(B)受体阴性。相反,我们的数据揭示了GABA(B)受体在胆碱能/γ-氨基丁酸能星爆无长突细胞上的定位。星爆无长突细胞上GABA(B)受体的高分辨率定位表明,它们离散地定位于其曲张体的有限群体中,大多数可能的突触释放位点没有可检测水平的GABA(B)受体。最后,我们鉴定出一个甘氨酸能细胞,它是GABA(B)调节的乙酰胆碱释放的潜在毒蕈碱受体-bearing靶标。这个靶标是DAPI - 3细胞。基于这些数据,我们提出对Neal和Cunningham模型的修改,其中GABA(B)受体位于星爆无长突细胞而非甘氨酸能无长突细胞上。