title: Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus.
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.
authors.affiliation: European Brain Research Institute, Rita Levi-Montalcini Foundation, Rome, Italy. Electronic address: d.mango@ebri.it.
authors.forename: D
authors.initials: D
authors.lastname: Mango
authors.affiliation: University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Braksator
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: European Brain Research Institute, Rita Levi-Montalcini Foundation, Rome, Italy; Sapienza University of Rome, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Marcelli
authors.affiliation: University of Rome Tor Vergata, Rome, Italy; I.R.C.C.S. Santa Lucia Foundation, Rome, Italy.
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: European Brain Research Institute, Rita Levi-Montalcini Foundation, Rome, Italy; Casa Cura Policlinico (CCP), Department of Neurorehabilitation Sciences, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Feligioni
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy; Sapienza University of Rome, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Z I
authors.initials: ZI
authors.lastname: Bashir
authors.affiliation: European Brain Research Institute, Rita Levi-Montalcini Foundation, Rome, Italy; University of Rome Tor Vergata, Rome, Italy. Electronic address: r.nistico@ebri.it.
authors.forename: R
authors.initials: R
authors.lastname: Nisticò
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000200:Action Potentials; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D036881:Long-Term Synaptic Depression; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D017966:Pyramidal Cells / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: ASIC; Electrophysiology; Hippocampus; LTD; mGlu receptors