GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling.

GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling.
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DOI:
10.1038/nn.3496
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发表时间:
2013-10
影响因子:
25
通讯作者:
Kasai, Haruo
Kasai, Haruo
中科院分区:
医学1区
文献类型:
--
作者:
Hayama, Tatsuya;Noguchi, Jun;Watanabe, Satoshi;Takahashi, Noriko;Hayashi-Takagi, Akiko;Ellis-Davies, Graham C. R.;Matsuzaki, Masanori;Kasai, Haruo

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活动依赖性竞争的突触在神经组织中起着关键作用,并经常促进GABA;然而,其细胞基础知之甚少。皮质锥体神经元的兴奋性突触形成于称为树突棘的小突起上,其表现出结构可塑性。我们使用双色uncaging的谷氨酸和GABA在大鼠海马CA 1区锥体神经元,发现脊柱收缩和消除显着促进的GABAA受体激活前不久的动作电位。GABA能抑制抑制胞质Ca 2+浓度的大量增加,而它保留了NMDA型受体产生的Ca 2+纳米结构域,这两者都是脊柱收缩所必需的。与棘增大不同,棘收缩扩散到相邻的棘(<15 μm)并与它们的增大竞争,这一过程涉及肌动蛋白解聚因子ADF/cofilin。因此,GABA能抑制直接抑制局部树突状细胞Ca 2+瞬变,并强烈促进树突棘的竞争性选择。
Activity-dependent competition of synapses plays a key role in neural organization and is often promoted by GABA; however, its cellular bases are poorly understood. Excitatory synapses of cortical pyramidal neurons are formed on small protrusions known as dendritic spines, which exhibit structural plasticity. We used two-color uncaging of glutamate and GABA in rat hippocampal CA1 pyramidal neurons and found that spine shrinkage and elimination were markedly promoted by the activation of GABAA receptors shortly before action potentials. GABAergic inhibition suppressed bulk increases in cytosolic Ca2+ concentrations, whereas it preserved the Ca2+ nanodomains generated by NMDA-type receptors, both of which were necessary for spine shrinkage. Unlike spine enlargement, spine shrinkage spread to neighboring spines (<15 μm) and competed with their enlargement, and this process involved the actin-depolymerizing factor ADF/cofilin. Thus, GABAergic inhibition directly suppresses local dendritic Ca2+ transients and strongly promotes the competitive selection of dendritic spines.
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