GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells
GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells
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DOI：
10.1073/pnas.1803490115
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发表时间：
2018-12-18
影响因子：
11.1
通讯作者：
Wong, Rachel O.
中科院分区：
文献类型：
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作者：
Bleckert, Adam;Zhang, Chi;Wong, Rachel O.
突触抑制通过两个亚细胞区室（细胞体和树突）的功能不同的输入来控制神经元的输出。目前还不清楚这些不同的抑制性输入的组装是否可以独立地通过神经传递进行调节。在哺乳动物视网膜中，γ-氨基丁酸（GABA）从星爆无长突细胞（SAC）释放到开-关方向选择性神经节细胞（ooDSGCs）的树突上是方向选择性反应所必需的。我们发现ooDSGCs也从其他无长突细胞（AC）接受GABA能输入，包括含有血管活性肠肽（VIP）的AC。当GABA能净传递减少时，ooDSGC上的体细胞而非树突GABA（A）受体簇的数量和大小增加。相关的荧光成像和系列电子显微镜显示，这些扩大的体细胞受体集群定位于突触。相比之下，选择性阻断囊泡GABA释放无论是SAC或VIP AC不改变树突状或体细胞受体分布上的ooDSGCs，表明无论是SAC或VIP AC GABA释放单独需要的抑制性突触的发展ooDSGCs。此外，减少净GABA能传输，但不是选择性减少从SAC，增加兴奋驱动到ooDSGCs。这种增加的兴奋可能驱动ooDSGC体细胞GABA（A）受体的稳态增加。ooDSGC的索马和树突上GABA（A）受体的差异调节可以促进ooDSGC输出的稳态控制，同时使方向选择性基础上的GABA能连接的组装对改变的传输无关紧要。
Synaptic inhibition controls a neuron's output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, gamma-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on-off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABA(A) receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABA(A) receptors. Differential regulation of GABA(A) receptors on the ooDSGC's soma and dendrites could facilitate homeostatic control of the ooDSGC's output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.