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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >AMPA receptors regulate experience-dependent dendritic arbor growth in vivo
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AMPA receptors regulate experience-dependent dendritic arbor growth in vivo

机译：AMPA受体调节体内依赖经验的树突状乔木的生长

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摘要

The size and shape of neuronal dendritic arbors affect the number and type of synaptic inputs, as well as the complexity and function of brain circuits. In the intact brain, dendritic arbor growth and the development of excitatory glutamatergic synapse are concurrent. Consequently, it has been difficult to resolve whether synaptic inputs drive dendritic arbor development. Here, we test the role of AMPA receptor (AMPAR)-mediated glutamatergic transmission in dendrite growth by expressing peptides corresponding to the intracellular C-terminal domains of AMPAR subunits GluR1 (GluR1Ct) and GluR2 (GluR2Ct) in optic tectal neurons of the Xenopus retinotectal system. These peptides significantly reduce AMPAR synaptic transmission in transfected neurons while leaving visual system circuitry intact. Daily in vivo imaging over 5 days revealed that GluR1Ct or GIuR2Ct expression dramatically impaired dendrite growth, resulting in less complex arbors than controls. Time-lapse images collected at 2-h intervals over 6 h show that both GluR1Ct and GIuR2Ct decrease branch lifetimes. Ultrastructural analysis indicates that synapses formed onto neurons expressing the GluRCt are less mature than synapses onto control neurons. These data suggest that the failure to form complex arbors is due to reduced stabilization of new synapses and dendritic branches. Although visual stimulation increases dendritic arbor growth rates in control tectal neurons, a weak postsynaptic response to visual experience in GluRCt-expressing cells leads to retraction of branches. These results indicate that AMPAR-mediated transmission underlies experience-dependent dendritic arbor growth by stabilizing branches, and support a competition-based model for dendrite growth.
机译：神经元树突状树突的大小和形状影响突触输入的数量和类型，以及脑回路的复杂性和功能。在完整的大脑中，树突状乔木的生长与兴奋性谷氨酸能突触的发展是同时发生的。因此，很难确定突触输入是否驱动树突状乔木发育。在这里，我们通过表达对应于非洲爪蟾视神经的视神经皮层神经细胞中AMPAR亚基GluR1（GluR1Ct）和GluR2（GluR2Ct）的胞内C端结构域的肽段来测试AMPA受体（AMPAR）介导的谷氨酸能传递在树突生长中的作用。系统。这些肽显着减少了转染神经元中的AMPAR突触传递，同时保持了视觉系统电路完整。超过5天的每日体内成像显示，GluR1Ct或GIuR2Ct的表达极大地损害了树枝状晶体的生长，从而导致树突的复杂程度低于对照组。在6小时内以2小时间隔收集的延时图像显示，GluR1Ct和GIuR2Ct均会降低分支寿命。超微结构分析表明，在表达GluRCt的神经元上形成的突触不如在对照神经元上的突触成熟。这些数据表明不能形成复杂的乔木是由于新突触和树突分支的稳定性降低。尽管视觉刺激增加了控制性顶盖神经元中树突状乔木的生长速度，但对表达GluRCt的细胞中视觉体验的突触后反应较弱，导致分支的收缩。这些结果表明，AMPAR介导的传播通过稳定分支而成为依赖经验的树枝状乔木生长的基础，并支持枝晶生长的基于竞争的模型。

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