Neuronal glutamate transporters control activation of postsynaptic metabotropic glutamate receptors and influence cerebellar long-term depression.
Neuronal and glial isoforms of glutamate transporters show distinct distributions on membranes surrounding excitatory synapses, but specific roles for transporter subtypes remain unidentified. At parallel fiber (PF) synapses in cerebellum, neuronal glutamate transporters and metabotropic glutamate receptors (mGluRs) have overlapping postsynaptic distributions suggesting that postsynaptic transporters selectively regulate mGluR activation. We examined interactions between transporters and mGluRs by evoking mGluR-mediated excitatory postsynaptic currents (mGluR EPSCs) in slices of rat cerebellum. Selective inhibition of postsynaptic transporters enhanced mGluR EPSCs greater than 3-fold. Moreover, impairing glutamate uptake facilitated mGluR-dependent long-term depression at PF synapses. Our results demonstrate that uniquely positioned glutamate transporters strongly influence mGluR activation at cerebellar PF synapses. Postsynaptic glutamate uptake may serve as a general mechanism for regulating mGluR-initiated synaptic depression.
Brasnjo
G
G
Department of Neurobiology and Brain Research Institute, School of Medicine, University of California, Los Angeles 90095, USA.
Otis
T S
TS
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D009412:Nerve Fibers / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011689:Purkinje Cells / Q000378:metabolism* / Q000648:ultrastructure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D001224:Aspartic Acid; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D005998:Glycine; D010852:Picrotoxin; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; D013779:Tetrodotoxin; C120673:benzyloxyaspartate; C079694:alpha-methyl-4-carboxyphenylglycine; C056723:FG 9041