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Modulation of glutamate release from parallel fibers by mGlu4 and pre‐synaptic GABA A receptors
Author(s) -
Antflick Jordan E.,
Hampson David R.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07611.x
Subject(s) - glutamate receptor , metabotropic glutamate receptor , muscimol , metabotropic receptor , chemistry , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 6 , receptor , gabaa receptor , glutamatergic , cerebellum , parallel fiber , metabotropic glutamate receptor 5 , long term depression , metabotropic glutamate receptor 2 , neurotransmission , metabotropic glutamate receptor 8 , biophysics , neuroscience , metabotropic glutamate receptor 7 , excitatory postsynaptic potential , biochemistry , biology , ampa receptor
J. Neurochem. (2012) 120 , 552–563. Abstract The regulation of pre‐synaptic glutamate release is important in the maintenance and fidelity of excitatory transmission in the nervous system. In this study, we report a novel interaction between a ligand‐gated ion channel and a G‐protein coupled receptor which regulates glutamate release from parallel fiber axon terminals. Immunocytochemical analysis revealed that GABA A receptors and the high affinity group III metabotropic glutamate receptor subtype 4 (mGlu4) are co‐localized on glutamatergic parallel fiber axon terminals in the cerebellum. GABA A and mGlu4 receptors were also found to co‐immunoprecipitate from cerebellar membranes. Independently, these two receptors have opposing roles on glutamate release: pre‐synaptic GABA A receptors promote, while mGlu4 receptors inhibit, glutamate release. However, coincident activation of GABA A receptors with muscimol and mGlu4 with the agonist (2 S )‐ S ‐2‐amino‐4‐phosphonobutanoic acid , increased glutamate release from [ 3 H]glutamate‐loaded cerebellar synaptosomes above that observed with muscimol alone. Further support for an interaction between GABA A and mGlu4 receptors was obtained in the mGlu4 knockout mouse which displayed reduced binding of the GABA A ligand [ 35 S] tert ‐butylbicyclophosphorothionate, and decreased expression of the α1, α6, β2 GABA A receptor subunits in the cerebellum. Taken together, our data suggest a new role for mGlu4 whereby simultaneous activation with GABA A receptors acts to amplify glutamate release at parallel fiber‐Purkinje cell synapses.