1] Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. [2] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. [3].
Nat Neurosci. 2013 Oct;16(10):1409-16. doi: 10.1038/nn.3496. Epub 2013 Aug 25.
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 Ca(2+) concentrations, whereas it preserved the Ca(2+) 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 Ca(2+) transients and strongly promotes the competitive selection of dendritic spines.
活动依赖性的突触竞争在神经组织中起着关键作用，通常由 GABA 促进；然而，其细胞基础还知之甚少。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，这些树突棘表现出结构可塑性。我们使用两种颜色的谷氨酸和 GABA 在大鼠海马 CA1 锥体神经元中的光解，发现 GABA 能受体的激活在动作电位之前很短的时间内显著促进了棘突的收缩和消除。GABA 能抑制抑制胞质钙离子浓度的整体增加，而保留由 NMDA 型受体产生的钙离子纳米区，这两者都是棘突收缩所必需的。与棘突增大不同，棘突收缩会扩散到邻近的棘突（<15 μm）并与它们的增大竞争，这个过程涉及到肌动蛋白解聚因子 ADF/cofilin。因此，GABA 能抑制直接抑制局部树突钙离子瞬变，并强烈促进树突棘的竞争选择。
