Research ArticleNeuroscience

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

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Science Signaling  07 Aug 2018:
Vol. 11, Issue 542, eaar4481
DOI: 10.1126/scisignal.aar4481

ASIC channels in motor learning

Members of the ASIC family of acid-sensing ion channels are abundant in various regions of the brain and mediate neuronal synaptic function. Yu et al. found that ASIC1a is present in neurons in the striatum. Manipulating ASIC1a expression in striatal neurons in mice revealed that this channel is critical for promoting the synaptic abundance and function of NMDA receptors in response to changes in extracellular pH. By activating a kinase-dependent transcriptional program that promotes the expression of NMDA receptor subunits, ASIC1a channels stimulate synaptic activity and dendritic spine maturation in the striatal neurons that facilitate motor learning. Mice lacking ASIC1a were slower to learn new motor coordination tasks. These findings may have implications for both neuronal development and neuronal disorders that affect the striatum and motor control.


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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