Department of Physiology & Biophysics, Center for Neuroscience, 124 Sherman Hall, 3435 Main Street, Buffalo, NY 14214, USA.
J Physiol. 2010 Dec 15;588(Pt 24):4937-49. doi: 10.1113/jphysiol.2010.194233. Epub 2010 Oct 25.
GABAergic amacrine cell feedback to bipolar cells in retina has been described, activating both GABA(A) and GABA(C) receptors. We explored whether metabotropic GABA(B) receptors also participate in this feedback pathway. CGP55845, a potent GABA(B) receptor antagonist, was employed to determine the endogenous role of these receptors. Ganglion cell EPSCs and IPSCs were monitored to measure the output of bipolar and amacrine cells. Using the tiger salamander slice preparation, we found that GABA(B) receptor pathways regulate bipolar cell release directly and indirectly. In the direct pathway, the GABA(B) receptor antagonist reduces EPSC amplitude, indicating that GABA(B) receptors cause enhanced glutamate release from bipolar cells to one set of ganglion cells. In the indirect pathway, the GABA(B) receptor antagonist reduces EPSC amplitude in another set of ganglion cells. The indirect pathway is only evident when GABA(A) receptors are inhibited, and is blocked by a glycine receptor antagonist. Thus, this second feedback pathway involves direct glycine feedback to the bipolar cell and this glycinergic amacrine cell is suppressed by GABAergic amacrine cells, through both GABA(A) and GABA(B) but not GABA(C) receptors. Overall, GABA(B) receptors do contribute to feedback regulation of bipolar cell transmitter release. However, unlike the ionotropic GABA receptor pathways, the metabotropic GABA receptor pathways act to enhance bipolar cell transmitter release. Furthermore, there are three discrete subsets of bipolar cell output regulated by GABA(B) receptor feedback (direct, indirect and null), implying three distinct, non-overlapping bipolar cell to ganglion cell circuits.
已经描述了视网膜中的 GABA 能无长突细胞对双极细胞的反馈，激活 GABA(A) 和 GABA(C) 受体。我们探讨了代谢型 GABA(B) 受体是否也参与这种反馈途径。CGP55845 是一种有效的 GABA(B) 受体拮抗剂，用于确定这些受体的内源性作用。使用虎纹蝾螈切片制备，我们发现 GABA(B) 受体途径直接和间接调节双极细胞释放。在直接途径中，GABA(B) 受体拮抗剂减少 EPSC 幅度，表明 GABA(B) 受体导致双极细胞从谷氨酸释放增强到一组节细胞。在间接途径中，GABA(B) 受体拮抗剂减少另一组节细胞的 EPSC 幅度。间接途径仅在 GABA(A) 受体被抑制时才明显，并且被甘氨酸受体拮抗剂阻断。因此，第二种反馈途径涉及直接甘氨酸反馈到双极细胞，并且这种 GABA 能无长突细胞被 GABA 能无长突细胞抑制，通过 GABA(A) 和 GABA(B) 但不是 GABA(C) 受体。总体而言，GABA(B) 受体确实有助于双极细胞递质释放的反馈调节。然而，与离子型 GABA 受体途径不同，代谢型 GABA 受体途径作用于增强双极细胞递质释放。此外，有三种离散的双极细胞输出子集受 GABA(B) 受体反馈调节（直接、间接和无），这意味着存在三种不同的、不重叠的双极细胞到节细胞回路。
