Blockade of glutamate transporters facilitates cerebellar synaptic long-term depression.
Excitatory amino acid transporters (EAATs) are believed to limit extracellular glutamate concentrations with specific roles poorly understood. At cerebellar climbing fiber-Purkinje cell synapse, EAAT4 and metabotropic glutamate receptor 1 (mGluR1) are closely expressed in surrounding postsynaptic locations, suggesting that EAAT4 may regulate mGluR1 activation. We examined the actions of EAAT4 on synaptic plasticity by applying blockers of glutamate transporters, DL-threo-beta-benzyloxyaspartic acid and D-aspartate. Inhibition of EAAT4 markedly prolonged AMPA receptor-mediated excitatory postsynaptic currents evoked by stimulating climbing fibers. Impairing glutamate uptake facilitated mGluR1-dependent climbing fiber-Purkinje cell synaptic long-term depression (LTD). Glutamate uptake blockers also sufficiently rescued climbing fiber-Purkinje cell synaptic LTD that failed to be induced by a weaker tetanus. Our results suggest that neuronal glutamate transporters strongly influence mGluR1-dependent cerebellar LTD.
Su
Li-Da
LD
Department of Neurobiology/Institute of Neuroscience, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Shen
Ying
Y
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D026603:D-Aspartic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D050581:Excitatory Amino Acid Transporter 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D050581:Excitatory Amino Acid Transporter 4; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; C493389:Slc1a6 protein, rat; C120673:benzyloxyaspartate; C104077:metabotropic glutamate receptor type 1; D001224:Aspartic Acid; D018698:Glutamic Acid; D026603:D-Aspartic Acid