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.

酸敏感离子通道 1a (ASIC1a) 在多个大脑区域中含量丰富，包括纹状体，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发挥着重要作用。我们研究了 ASIC1a 在纹状体神经元中的功能作用。我们发现 ASIC1a 通过调节纹状体中型多棘神经元的突触可塑性，对于纹状体依赖性运动协调和程序学习至关重要。小鼠中Asic1a的整体缺失导致树突棘密度增加，但树突棘形态和突触后结构受损，同时伴有兴奋性突触N-甲基-d-天冬氨酸 (NMDA) 受体功能下降。ASIC1a 缺失引起的这些结构和功能变化主要是由 Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II (CaMKII) 和细胞外信号调节蛋白激酶 (ERK) 激活（磷酸化）减少介导的。因此，Asic1a缺失小鼠在多项运动任务中表现不佳，但纹状体特异性表达 ASIC1a 或 CaMKII 可以挽救这种情况。总之，我们的数据揭示了一种由 ASIC1a 介导的先前未知的机制，该机制可促进纹状体相关程序性学习和记忆的兴奋性突触功能。