Role of glutamate transporters in corticostriatal synaptic transmission.
High-affinity glutamate transporters (GTs) play a major role in controlling the extracellular level of this excitatory neurotransmitter in the CNS. Here we have characterized, by means of in vitro patch-clamp recordings from medium spiny neurons (MSNs), the role of GTs in regulating corticostriatal glutamatergic synaptic transmission in the adult rat. Charge transfer and decay-time, but not amplitude, of excitatory postsynaptic currents (EPSCs) were enhanced by dl-threo-beta-benzyloxyaspartate (TBOA), a broad inhibitor of GTs. Moreover, TBOA also potentiated currents induced by high-frequency stimulation (HFS) protocols. Interestingly, the effect of TBOA on EPSCs was lost when MSNs were clamped at +40 mV, a condition in which neuronal GTs, that are voltage-dependent, are blocked. However, in this condition TBOA was still able to enhance HFS-induced currents, suggesting that glial GT's role is to regulate synaptic transmission when glutamate release is massive. These data suggest that neuronal GTs, rather than glial, shape EPSCs' kinetics and modulate glutamate transmission at corticostriatal synapse. Moreover, the control of glutamate concentration in the synaptic cleft by GTs may play a role in a number of degenerative disorders characterized by the hyperactivity of corticostriatal pathway, as well as in synaptic plasticity.
Beurrier
C
C
Institut de Biologie du Développement de Marseille-Luminy, Marseille, France.
Bonvento
G
G
Kerkerian-Le Goff
L
L
Gubellini
P
P
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001703:Biophysics; D002540:Cerebral Cortex / Q000166:cytology*; D003342:Corpus Striatum / Q000166:cytology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014161:Transduction, Genetic / Q000379:methods
D027322:Amino Acid Transport System X-AG; D018691:Excitatory Amino Acid Antagonists; C120673:benzyloxyaspartate; C474696:methyl-(4-carboxyphenyl)glycine; D049452:Green Fluorescent Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D005998:Glycine