Li L, Chin L S, Shupliakov O, Brodin L, Sihra T S, Hvalby O, Jensen V, Zheng D, McNamara J O, Greengard P
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9235-9. doi: 10.1073/pnas.92.20.9235.
Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exocytosis. 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 and 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.
有人提出，突触蛋白I通过控制突触小泡用于胞吐作用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小泡组织明显改变：紧密堆积的小泡仅存在于活性区的狭窄边缘，而大多数小泡分散在整个末梢区域。这与野生型动物末梢中存在的有组织的小泡簇形成对比。在突触蛋白I突变小鼠中，由K⁺、4-氨基吡啶或Ca²⁺离子载体诱导的神经末梢谷氨酸释放明显减少。高频刺激耗尽神经递质后突触传递的恢复大大延迟。最后，通过脑电图和行为性癫痫发作测量，突触蛋白I缺陷小鼠对电刺激的反应显著增加。这些结果为突触蛋白I在成熟突触中神经末梢功能调节中起关键作用的假说提供了有力支持。
