IMPAIRMENT OF SYNAPTIC VESICLE CLUSTERING AND OF SYNAPTIC TRANSMISSION, AND INCREASED SEIZURE PROPENSITY, IN SYNAPSIN I-DEFICIENT MICE
IMPAIRMENT OF SYNAPTIC VESICLE CLUSTERING AND OF SYNAPTIC TRANSMISSION, AND INCREASED SEIZURE PROPENSITY, IN SYNAPSIN I-DEFICIENT MICE
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DOI：
10.1073/pnas.92.20.9235
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发表时间：
1995-09-26
影响因子：
11.1
通讯作者：
ANDERSEN, P
中科院分区：
文献类型：
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作者：
LI, L;CHIN, LS;ANDERSEN, P
已经提出突触蛋白I通过控制突触囊泡的可用性来参与神经递质释放的调节。为了进一步了解突触蛋白I在成年神经末梢功能中的作用，我们研究了通过同源重组产生的突触蛋白I缺陷小鼠，突触蛋白I缺陷小鼠突触前末梢的突触囊泡组织显著改变：密集包装的囊泡仅存在于活性区的狭窄边缘，而大多数囊泡分散在整个终末区域，这与有组织的相反;在突触蛋白I突变小鼠中，由K+、4-氨基吡啶或Ca 2+离子载体诱导的神经末梢的谷氨酸释放显著减少，在高频刺激耗尽神经递质后突触传递的恢复大大延迟，最后，突触蛋白I缺陷的小鼠表现出对电刺激的显著增加的反应，如通过电描记酸行为癫痫发作所测量的。这些结果为突触蛋白I在成熟突触的神经末梢功能的调节中起关键作用的假说提供了强有力的支持。
Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exofytosis. To further understand the role of synapsin I in the function of adult nerve terminals, we studied synapsin I-deficient mice generated by homologous recombination, The organization of synaptic vesicles at presynaptic terminals of synapsin I-deficient mice was markedly altered: densely packed vesicles were only present in a narrow rim at active zones, whereas the majority of vesicles were dispersed throughout the terminal area, This was in contrast to the organized;vesicle clusters present in terminals of wild-type animals, Release of glutamate from nerve endings, induced by K+, 4-aminopyridine, or a Ca2+ ionophore, was markedly decreased in synapsin I mutant mice, The recovery of synaptic transmission after depletion of neurotransmitter by high-frequency stimulation was greatly delayed, Finally, synapsin I-deficient mice exhibited a strikingly increased response to electrical stimulation, as measured by electrographic acid behavioral seizures, These results provide strong support for the hypothesis that synapsin I plays a key role in the regulation of nerve terminal function in mature synapses.