Glial glutamate transporters maintain one-to-one relationship at the climbing fiber-Purkinje cell synapse by preventing glutamate spillover.
J Neurosci
; 26(24): 6563-72, 2006 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-16775144
A glial glutamate transporter, GLAST, is expressed abundantly in Bergmann glia and plays a major role in glutamate uptake at the excitatory synapses in cerebellar Purkinje cells (PCs). It has been reported that a higher percentage of PCs in GLAST-deficient mice are multiply innervated by climbing fibers (CFs) than in the wild-type (WT) mice, and that CF-mediated EPSCs with small amplitude and slow rise time, designated as atypical slow CF-EPSCs, are observed in these mice. To clarify the mechanism(s) underlying the generation of these atypical CF-EPSCs, we used (2S,3S)-3-[3-(4-methoxybenzoylamino)benzyloxy]aspartate (PMB-TBOA), an inhibitor of glial glutamate transporters. After the application of PMB-TBOA, slow-rising CF-EPSCs were newly detected in WT mice, and their rise and decay kinetics were different from those of conventional fast-rising CF-EPSCs but similar to those of atypical CF-EPSCs in GLAST-deficient mice. Furthermore, both slow-rising CF-EPSCs in the presence of PMB-TBOA in WT mice and atypical CF-EPSCs in GLAST-deficient mice showed much greater paired-pulse depression compared with fast-rising CF-EPSCs. In addition, both of them were more markedly inhibited by gamma-d-glutamyl-glycine, a low-affinity competitive antagonist of AMPA receptors. These results indicated that both of these types of EPSCs were mediated by a low concentration of glutamate released from neighboring CFs. Based on all of these findings, we suggest that glial transporters prevent glutamate released from a single CF from spilling over to neighboring PCs other than the synaptically connected PC, and play an essential role in the maintenance of the functional one-to-one relationship between CFs and PCs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células de Purkinje
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Sinapsis
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Ácido Glutámico
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Transportador 1 de Aminoácidos Excitadores
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Fibras Nerviosas
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Inhibición Neural
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos