In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice

In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice
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DOI:
10.1523/jneurosci.2073-11.2011
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发表时间:
2011-10-26
影响因子:
5.3
通讯作者:
Brose, Nils
Brose, Nils
中科院分区:
医学1区
文献类型:
--
作者:
Herzog, Etienne;Nadrigny, Fabien;Brose, Nils

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囊泡谷氨酸转运蛋白 VGLUT1 将神经递质谷氨酸装载到突触囊泡中,从而决定哺乳动物大脑中许多突触的谷氨酸释放。由于其功能和选择性定位,VGLUT1 是谷氨酸能突触小泡最特异的标记物之一。它已被广泛用于识别谷氨酸能突触,其表达水平与量子大小的变化、突触可塑性的调节和相应的行为密切相关。我们生成了荧光 VGLUT1(Venus) 敲入小鼠,用于分析 VGLUT1 和谷氨酸突触小泡运输。该突变不会影响谷氨酸能突触功能,因此新的小鼠模型代表了分析前脑谷氨酸能递质系统的通用工具。先前的研究证明了体外突触末梢之间的突触小泡交换。使用 VGLUT1(Venus) 敲入,我们发现突触小泡在体内小鼠皮质中的 bouton 之间动态共享。我们对体外突触小泡共享进行了详细分析,并表明网络稳态导致突触 VGLUT1 水平的动态缩放。
The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synaptic vesicles. It has been used widely to identify glutamatergic synapses, and its expression levels are tightly correlated with changes in quantal size, modulations of synaptic plasticity, and corresponding behaviors. We generated a fluorescent VGLUT1(Venus) knock-in mouse for the analysis of VGLUT1 and glutamatergic synaptic vesicle trafficking. The mutation does not affect glutamatergic synapse function, and thus the new mouse model represents a universal tool for the analysis of glutamatergic transmitter systems in the forebrain. Previous studies demonstrated synaptic vesicle exchange between terminals in vitro. Using the VGLUT1(Venus) knock-in, we show that synaptic vesicles are dynamically shared among boutons in the cortex of mice in vivo. We provide a detailed analysis of synaptic vesicle sharing in vitro, and show that network homeostasis leads to dynamic scaling of synaptic VGLUT1 levels.