Piccolo knockdown-induced impairments of spatial learning and long-term potentiation in the hippocampal CA1 region
Piccolo knockdown-induced impairments of spatial learning and long-term potentiation in the hippocampal CA1 region
复制标题
Piccolo 敲低引起海马 CA1 区空间学习和长期增强的损害。
DOI：
10.1016/j.neuint.2009.09.004
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Ito, Yoshihisa
中科院分区：
文献类型：
--
作者：
Ibi, Daisuke;Nitta, Atsumi;Ito, Yoshihisa
神经递质的释放是在神经末梢一个被称为“活性区”的特定部位进行调控的，该区域由多种细胞基质蛋白组成，如短笛蛋白（也称为Aczonin）和巴松管蛋白。这些蛋白具有高度相似的序列区域，且分子量极大（>400 kDa）。由于短笛蛋白基因敲除小鼠模型尚未建立，短笛蛋白在神经系统中的作用仍不明确。在本研究中，我们将短笛蛋白反义寡核苷酸注入脑室，通过新物体识别测试和莫里斯水迷宫测试，探究其对海马体长期增强效应（LTP）以及学习记忆能力的影响。接受短笛蛋白反义寡核苷酸处理的小鼠与接受载体或正义寡核苷酸处理的小鼠相比，认知记忆方面无显著差异；然而，接受短笛蛋白反义寡核苷酸处理的小鼠空间学习能力受损，而接受正义寡核苷酸或载体处理的小鼠则未出现此情况。接下来，我们在相同海马体切片的CA1区和齿状回中研究了这些组别的LTP形成情况。接受短笛蛋白反义寡核苷酸处理的小鼠，其LTP强度显著低于接受正义寡核苷酸或载体处理的小鼠，而基础水平并无变化。此外，接受反义寡核苷酸处理的小鼠在高钾诱导下的谷氨酸释放水平显著低于接受正义寡核苷酸处理的小鼠。综上所述，这些结果表明，短笛蛋白在小鼠CA1区的突触可塑性以及海马体依赖的学习过程中起着关键作用，并且在刺激条件下，海马体中细胞外谷氨酸水平受短笛蛋白调控。（C）2009爱思唯尔有限公司 保留所有权利。
Neurotransmitter release is regulated at a specific site in nerve terminals called the "active zone", which is composed of various cytomatrix proteins such as Piccolo (also known as Aczonin) and Bassoon. These proteins share regions of high sequence similarity and have very high molecular weights (>400 kDa). Since Piccolo knockout mice have not yet been established, the role of Piccolo in the neuronal system remains unclear. In this study, we investigated the effects of Piccolo antisense oligonucleotide injected into the ventricle on hippocampal long-term potentiation (LTP) and learning and memory assessed with the novel object recognition test and the Morris water maze test. There was no significant difference in cognitive memory between Piccolo antisense-treated and vehicle- or sense-treated mice; however, spatial learning in Piccolo antisense-treated mice was impaired but not in sense- or vehicle-treated mice. Next, we investigated LTP formation in these groups in area CA1 and dentate gyrus of the same hippocampal slices. The magnitude of LTP in Piccolo antisense-treated mice was significantly lower than in sense- or vehicle-treated mice, with no change in basal level. Moreover, the level of high K+-induced glutamate release in the antisense-treated mice was significantly lower than in sense-treated mice. Taken together, these results indicate that Piccolo plays a pivotal role in synaptic plasticity in area CA1 and in hippocampus-dependent learning in mice, and that the extracellular levels of glutamate in the hippocampus under stimulated conditions are controlled by Piccolo. (C) 2009 Elsevier Ltd. All rights reserved.