Glutamate spillover in the striatum depresses dopaminergic transmission by activating group I metabotropic glutamate receptors.
Cortical glutamate and substantia nigra dopamine (DA) afferents converge onto the dendritic spines of medium spiny neurons (MSNs) in the striatum where they act to modulate motor and cognitive functions. The released DA spills over from its synapse and is thought to regulate glutamatergic input by acting on distal DA receptors located on corticostriatal axon terminals. By monitoring evoked DA release directly using fast-scan cyclic voltammetry, we report a reciprocal modulation by glutamate spillover on evoked striatal DA release, induced by either glutamate uptake blockade or high-frequency stimulation of corticostriatal tracts. We demonstrate that this modulation is attributable to the activation of group I metabotropic glutamate receptors. Thus, under conditions in which glutamate escapes the confines of its synapse, it can elicit the presynaptic suppression of dopaminergic neurotransmission.
Zhang
Hui
H
Department of Neurology, Columbia University, New York, New York 10032, USA.
Sulzer
David
D
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000037:antagonists & inhibitors; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000502:physiology*
D027322:Amino Acid Transport System X-AG; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D008024:Ligands; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D027981:Symporters; C104077:metabotropic glutamate receptor type 1; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine; D004298:Dopamine