LAUSR

Graphical abstract Figure. No Caption available. ABSTRACT Acid‐sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor‐dependent long‐term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30‐40 animals, since the ASIC1a selective blocker psalmotoxin‐1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)‐3,5‐Dihydroxyphenylglycine (DHPG) or induced by paired‐pulse low frequency stimulation (PP‐LFS). Conversely, PcTx1 did not affect LTD in P13‐18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor‐induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG‐induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post‐synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.