title: Calcium-permeable presynaptic AMPA receptors in cerebellar molecular layer interneurones.
abstract: Axons of cerebellar molecular layer interneurones (MLIs) bear ionotropic glutamate receptors. Here, we show that these receptors elicit cytosolic [Ca2+] transients in axonal varicosities following glutamate spillover induced by stimulation of parallel fibres (PFs). A spatial profile analysis indicates that these transients occur at the same locations when induced by PF stimulation or trains of action potentials. They are not affected by the NMDAR antagonist AP-V, but are abolished by the AMPAR inhibitor GYKI-53655. Mimicking glutamate spillover by a puff of AMPA triggers axonal [Ca2+]i transients even in the presence of TTX. Addition of specific voltage-dependent Ca2+ channel (VDCC) blockers such as omega-AGAIVA and omega-conotoxin GVIA or broad range inhibitors such as Cd2+ did not significantly inhibit the signal indicating the involvement of Ca2+-permeable AMPARs. This hypothesis is further supported by the finding that the subunit specific AMPAR antagonist IEM-1460 blocks 75% of the signal. Bath application of AMPA increases the frequency and mean peak amplitude of GABAergic mIPSCs, an effect that is blocked by philanthotoxin-433 (PhTx) and reinforced by facilitating concentrations of ryanodine. By contrast, a high concentration of ryanodine or dantrolene reduced the effects of AMPA on mIPSCs. Single-cell RT-PCR experiments show that all GluR1-4 subunits are potentially expressed in MLI. Taken together, the results suggest that Ca2+-permeable AMPARs are colocalized with VDCCs in axonal varicosities and can be activated by glutamate spillover through PF stimulation. The AMPAR-mediated Ca2+ signal is amplified by Ca2+-induced Ca2+ release from intracellular stores, leading to GABA release by MLIs.
authors.affiliation: Laboratoire de Physiologie Cérébrale, CNRS-UMR 8118, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Rossi
authors.forename: Gilliane
authors.initials: G
authors.lastname: Maton
authors.forename: Thibault
authors.initials: T
authors.lastname: Collin
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology*; D005786:Gene Expression Regulation / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D011689:Purkinje Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D012433:Ryanodine; D002118:Calcium
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