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The acid-sensing ion channel ASIC1a mediates striatal synapse remodeling and procedural motor learning.


ABSTRACT: 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.

SUBMITTER: Yu Z 

PROVIDER: S-EPMC6324561 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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The acid-sensing ion channel ASIC1a mediates striatal synapse remodeling and procedural motor learning.

Yu Zhe Z   Wu Yan-Jiao YJ   Wang Yi-Zhi YZ   Liu Di-Shi DS   Song Xing-Lei XL   Jiang Qin Q   Li Ying Y   Zhang Siyu S   Xu Nan-Jie NJ   Zhu Michael Xi MX   Li Wei-Guang WG   Xu Tian-Le TL  

Science signaling 20180807 542


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 <i>Asic1a</i> in mi  ...[more]

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