The acid-sensing ion channel ASIC1a mediates striatal synapse remodeling and procedural motor learning.
The acid-sensing ion channel ASIC1a mediates striatal synapse remodeling and procedural motor learning.
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酸敏感离子通道 ASIC1a 介导纹状体突触重塑和程序性运动学习
DOI：
10.1126/scisignal.aar4481
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发表时间：
2018-08-07
影响因子：
7.3
通讯作者：
Xu TL
中科院分区：
文献类型：
--
作者：
Yu Z;Wu YJ;Wang YZ;Liu DS;Song XL;Jiang Q;Li Y;Zhang S;Xu NJ;Zhu MX;Li WG;Xu TL
酸敏感离子通道1a（ASIC1a）在包括纹状体在内的多个脑区大量存在。纹状体作为基底神经节的输入核，在程序性学习和运动记忆中起着关键作用。我们探究了ASIC1a在纹状体神经元中的功能作用。我们发现，ASIC1a通过调节纹状体中等多棘神经元的突触可塑性，对依赖纹状体的运动协调和程序性学习至关重要。小鼠中Asic1a的全身性缺失导致树突棘密度增加，但棘形态和突触后结构受损，同时兴奋性突触处N - 甲基 - D - 天冬氨酸（NMDA）受体功能下降。ASIC1a缺失所引发的这些结构和功能变化，很大程度上是由Ca²⁺/钙调蛋白依赖性蛋白激酶II（CaMKII）和细胞外信号调节激酶（ERKs）激活（磷酸化）减少所介导的。因此，Asic1a基因敲除小鼠在多项运动任务中表现不佳，而通过纹状体内特异性表达ASIC1a或CaMKII可改善这一状况。总之，我们的数据揭示了一种此前未知的由ASIC1a介导的机制，该机制可促进与纹状体相关的程序性学习和记忆所依赖的兴奋性突触功能。
Acid-sensing ion channel 1a (ASIC1a) is abundant in multiple brain regions, including the striatum, which serves as the input nucleus of the basal ganglia and is critically involved in procedural learning and motor memory. We investigated the functional role of ASIC1a in striatal neurons. We found that ASIC1a was critical for striatum-dependent motor coordination and procedural learning by regulating the synaptic plasticity of striatal medium spiny neurons. Global deletion of Asic1a in mice led to increased dendritic spine density but impaired spine morphology and postsynaptic architecture, which were accompanied by the decreased function of N-methyl-D-aspartate (NMDA) receptors at excitatory synapses. These structural and functional changes caused by the loss of ASIC1a were largely mediated by reduced activation (phosphorylation) of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal–regulated protein kinases (ERKs). Consequently, Asic1a null mice exhibited poor performance on multiple motor tasks, which was rescued by striatal-specific expression of either ASIC1a or CaMKII. Together, our data reveal a previously unknown mechanism mediated by ASIC1a that promotes the excitatory synaptic function underlying striatum-related procedural learning and memory.
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影响因子：
5.7
作者：
Chen JL;Nedivi E
通讯作者：
Nedivi E
DOI：
10.1073/pnas.85.9.3260
发表时间：
1988-05-01
影响因子：
11.1
作者：
GEINISMAN, Y;MORRELL, F;DETOLEDOMORRELL, L
通讯作者：
DETOLEDOMORRELL, L
影响因子：
4.6
作者：
Chiang PH;Chien TC;Chen CC;Yanagawa Y;Lien CC
通讯作者：
Lien CC
影响因子：
25
作者：
Kreple, Collin J.;Lu, Yuan;Wemmie, John A.
通讯作者：
Wemmie, John A.
影响因子：
5.3
作者：
Gonzalez-Inchauspe, Carlota;Urbano, Francisco J.;Uchitel, Osvaldo D.
通讯作者：
Uchitel, Osvaldo D.