Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA.
J Neurosci. 2010 Feb 10;30(6):2330-9. doi: 10.1523/JNEUROSCI.5574-09.2010.
GABAergic feedback inhibition from amacrine cells shapes visual signaling in the inner retina. Rod bipolar cells (RBCs), ON-sensitive cells that depolarize in response to light increments, receive reciprocal GABAergic feedback from A17 amacrine cells and additional GABAergic inputs from other amacrine cells located laterally in the inner plexiform layer. The circuitry and synaptic mechanisms underlying lateral GABAergic inhibition of RBCs are poorly understood. A-type and rho-subunit-containing (C-type) GABA receptors (GABA(A)Rs and GABA(C)Rs) mediate both forms of inhibition, but their relative activation during synaptic transmission is unclear, and potential interactions between adjacent reciprocal and lateral synapses have not been explored. Here, we recorded from RBCs in acute slices of rat retina and isolated lateral GABAergic inhibition by pharmacologically ablating A17 amacrine cells. We found that amacrine cells providing lateral GABAergic inhibition to RBCs receive excitatory synaptic input mostly from ON bipolar cells via activation of both Ca(2+)-impermeable and Ca(2+)-permeable AMPA receptors (CP-AMPARs) but not NMDA receptors (NMDARs). Voltage-gated Ca(2+) (Ca(v)) channels mediate the majority of Ca(2+) influx that triggers GABA release, although CP-AMPARs contribute a small component. The intracellular Ca(2+) signal contributing to transmitter release is amplified by Ca(2+)-induced Ca(2+) release from intracellular stores via activation of ryanodine receptors. Furthermore, lateral nonreciprocal feedback is mediated primarily by GABA(C)Rs that are activated independently from receptors mediating reciprocal feedback inhibition. These results illustrate numerous physiological differences that distinguish GABA release at reciprocal and lateral synapses, indicating complex, pathway-specific modulation of RBC signaling.
从无长突细胞到 GABA 能反馈抑制来塑造视网膜内层的视觉信号。光感受器双极细胞（RBCs）是对光增强反应去极化的 ON 敏感细胞，它们接受来自 A17 无长突细胞的 GABA 能反馈抑制以及来自内侧内丛状层中其他无长突细胞的额外 GABA 能输入。RBCs 中横向 GABA 能抑制的电路和突触机制尚未完全了解。A 型和 rho 亚基（C 型）GABA 受体（GABA(A)Rs 和 GABA(C)Rs）介导这两种形式的抑制，但它们在突触传递过程中的相对激活尚不清楚，并且相邻的相互和横向突触之间的潜在相互作用尚未被探索。在这里，我们在急性大鼠视网膜切片中记录 RBCs，并通过药理学方法消除 A17 无长突细胞来分离横向 GABA 能抑制。我们发现，向 RBCs 提供横向 GABA 能抑制的无长突细胞主要通过激活 Ca(2+)不可渗透和 Ca(2+)可渗透 AMPA 受体（CP-AMPARs）而不是 NMDA 受体（NMDARs），从 ON 双极细胞接收兴奋性突触输入。电压门控 Ca(2+)（Ca(v)）通道介导触发 GABA 释放的大部分 Ca(2+)内流，尽管 CP-AMPARs 贡献了一小部分。通过激活肌醇 1,4,5-三磷酸受体（ryanodine receptors），来自细胞内储存库的 Ca(2+)-诱导的 Ca(2+)释放放大了导致递质释放的细胞内 Ca(2+)信号。此外，横向非相互反馈主要由 GABA(C)Rs 介导，其独立于介导相互反馈抑制的受体激活。这些结果说明了区分相互和横向突触处 GABA 释放的许多生理差异，表明 RBC 信号的复杂、特定途径的调制。
