A microfluidic based in vitro model of synaptic competition

A microfluidic based in vitro model of synaptic competition
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DOI:
10.1016/j.mcn.2014.03.001
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发表时间:
2014-05-01
影响因子:
3.5
通讯作者:
Cynader, Max
Cynader, Max
中科院分区:
医学3区
文献类型:
--
作者:
Coquinco, Ainsley;Kojic, Luba;Cynader, Max

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突触竞争被广泛认为是神经元网络形成和功能的核心,但其潜在机制却很少被描述。为了研究突触竞争,我们利用3室微流体装置建立了一种新的双输入通路竞争模型。来自两个不同外侧室(输入)的培养大鼠皮层神经元轴突支配一个独立中央室的共同神经元群。使用GABA(A)R激动剂muscimol抑制一个输入的活性,导致中央室中相反的未处理(未抑制)输入的突触数量和轴突伸长增加。延时成像显示,未受抑制的输入超出了受抑制的输入。这种形式的竞争发生在21 DIV之前结束的敏感时期,并且依赖于NMDAR和CamKII。令人惊讶的是,这种形式的可塑性取决于中央隔室神经元的年龄,而不是竞争输入。(C) 2014爱思唯尔公司版权所有。
Synaptic competition is widely believed to be central to the formation and function of neuronal networks, yet the underlying mechanisms are poorly described. To investigate synaptic competition in vitro, we have developed a novel two input pathway competition model using a 3-compartment microfluidic device. Axons from cultured rat cortical neurons from two different lateral compartments (inputs) innervate a common neuronal population in a separate central compartment. Inhibiting one input's activity, using the GABA(A)R agonist muscimol, resulted in increased synapse numbers and axon elongation of the opposing untreated (uninhibited) inputs in the central compartment. Time lapse imaging revealed that uninhibited inputs outgrew and outconnected their inhibited counterparts. This form of competition occurs during a sensitive period ending prior to 21 DIV and is NMDAR and CamKII dependent. Surprisingly, this form of plasticity was dependent on the age of the center compartment neurons but not of the competing inputs. (C) 2014 Elsevier Inc. All rights reserved.