Department of Biological Structure, University of Washington, Seattle, WA 98195.
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195.
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):E12083-E12090. doi: 10.1073/pnas.1803490115. Epub 2018 Dec 3.
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, γ-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 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 receptors. Differential regulation of GABA 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.
突触抑制通过在两个亚细胞隔室（胞体和树突）的功能不同的输入来控制神经元的输出。目前尚不清楚这些不同的抑制性输入的集合是否可以通过神经递质传递独立地进行调节。在哺乳动物视网膜中，星形胶质细胞（SAC）从星爆型无长突细胞（SAC）释放γ-氨基丁酸（GABA）到开/关方向选择性神经节细胞（ooDSGC）的树突上，对于方向选择性反应至关重要。我们发现，ooDSGC 还从其他无长突细胞（AC）接收 GABA 能输入，包括含有血管活性肠肽（VIP）的 AC。当净 GABA 能传递减少时，ooDSGC 上的体部，而不是树突部，GABA 受体簇的数量和大小增加。相关荧光成像和连续电子显微镜显示，这些扩大的体部受体簇定位于突触。相比之下，选择性地阻断 SAC 或 VIP AC 中的囊泡 GABA 释放都不会改变 ooDSGC 上的树突或体部受体分布，表明 SAC 或 VIP AC 单独的 GABA 释放都不是 ooDSGC 中抑制性突触发育所必需的。此外，净 GABA 能传递的减少，但不是 SAC 的选择性减少，增加了对 ooDSGC 的兴奋性驱动。这种增加的兴奋可能会驱动 ooDSGC 体部 GABA 受体的同型调节增加。ooDSGC 体部和树突上 GABA 受体的差异调节可以促进 ooDSGC 输出的同型调节，同时使方向选择性的 GABA 能连接的集合不受改变的传递影响。
