Contribution of glutamate transporter GLT-1 to removal of synaptically released glutamate at climbing fiber-Purkinje cell synapses.

Abstract:

:Rapid removal of synaptically released glutamate from the extracellular space ensures a high signal-to-noise ratio in excitatory neurotransmission. In the cerebellum, glial glutamate transporters, GLAST and GLT-1, are co-localized in the processes of Bergmann glia wrapping excitatory synapses on Purkinje cells (PCs). Although GLAST is expressed six-fold more abundantly than GLT-1, the decay kinetics of climbing fiber-mediated excitatory postsynaptic currents (CF-EPSCs) in PCs in GLAST(-/-) mice are not different from those in wild-type (WT) mice. This raises a possibility that GLT-1 plays a significant role in clearing glutamate at CF-PC synapses despite its smaller amount of expression. Here, we studied the functions of GLT-1 and GLAST in the clearance of glutamate using GLAST(-/-) mice and GLT-1(-/-) mice. In the presence of cyclothiazide (CTZ) that attenuates the desensitization of AMPA receptors, the decay time constant of CF-EPSCs (tau(w)) in GLT-1(-/-) mice was slower than that in WT mice. However, the degree of this prolongation of tau(w) was less prominent compared to that in GLAST(-/-) mice. The values of tau(w) in GLT-1(-/-) mice and GLAST(-/-) mice were comparable to those estimated in WT mice in the presence of a potent blocker of glial glutamate transporters (2S,3S)-3-[3-(4-methoxybenzoylamino)benzyloxy]aspartate (PMB-TBOA) at 10 and 100 nM, which reduced the amplitudes of glutamate transporter currents elicited by CF stimulation in Bergmann glia to approximately 81 and approximately 28%, respectively. We conclude that GLT-1 plays a minor role compared to GLAST in clearing synaptically released glutamate at CF-PC synapses.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Takatsuru Y,Iino M,Tanaka K,Ozawa S

doi

10.1016/j.neulet.2007.04.062

subject

Has Abstract

pub_date

2007-06-08 00:00:00

pages

85-9

issue

1

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(07)00528-9

journal_volume

420

pub_type

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