Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat retina.
Mechanisms underlying lateral GABAergic feedback onto rod bipolar cells in rat retina.
复制标题
DOI：
10.1523/jneurosci.5574-09.2010
复制
发表时间：
2010-02-10
期刊：
影响因子：
--
通讯作者：
Diamond JS
中科院分区：
文献类型：
--
作者：
Chávez AE;Grimes WN;Diamond JS
来自无长突细胞的GABA能反馈抑制形成视网膜内层的视觉信号。视杆双极细胞（RBC）是一种ON敏感细胞，对光照增加作出反应，接受来自A17无长突细胞的相互GABA能反馈和来自位于IPL侧面的其他无长突细胞的额外GABA能输入。红细胞外侧GABA能抑制的电路和突触机制知之甚少。A型和含ρ亚基（C型）GABA受体（GABAAR和GABACR）介导两种形式的抑制，但它们在突触传递过程中的相对激活尚不清楚，相邻的相互和侧向突触之间的潜在相互作用尚未被探索。在这里，我们记录了大鼠视网膜急性切片中的RBC，并通过切除A17无长突细胞来分离外侧GABA能抑制。我们发现，无长突细胞提供横向GABA能抑制红细胞接受兴奋性突触输入主要是从ON双极细胞通过激活两个Ca 2 +-不可渗透和Ca 2 +-可渗透的AMPAR受体（CP-AMPAR），但不是NMDA受体（NMDARs）。电压门控Ca 2+（Cav）通道介导触发GABA释放的大部分Ca 2+内流，尽管CP-AMPAR贡献了一小部分。通过激活兰尼碱受体（RyRs），由细胞内钙库中钙诱导的钙释放（CICR）放大了促进递质释放的细胞内钙信号。此外，侧向非相互反馈主要由GABACR介导，GABACR独立于介导相互反馈抑制的受体而被激活。这些结果说明了许多生理差异，区分GABA的释放在相互和横向突触，表明复杂的，特定的RBC信号通路的调制。
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 IPL. The circuitry and synaptic mechanisms underlying lateral GABAergic inhibition of RBCs are poorly understood. A-type and ρ subunit-containing (C-type) GABA receptors (GABAARs and GABACRs) 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 Ca2+-impermeable and Ca2+-permeable AMPAR receptors (CP-AMPARs) but not NMDA receptors (NMDARs). Voltage-gated Ca2+ (Cav) channels mediate the majority of Ca2+ influx that triggers GABA release, although CP-AMPARs contribute a small component. The intracellular Ca2+ signal contributing to transmitter release is amplified by Ca2+-induced Ca2+ release (CICR) from intracellular stores via activation of ryanodine receptors (RyRs). Furthermore, lateral non-reciprocal feedback is mediated primarily by GABACRs 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.