Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses

Yukihiro Takayasu, Masae Iino, Wataru Kakegawa, Hiroshi Maeno, Kei Watase, Keiji Wada, Dai Yanagihara, Taisuke Miyazaki, Okiru Komine, Masahiko Watanabe, Kohichi Tanaka, Seiji Ozawa

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Glutamate transporters are essential for terminating excitatory neurotransmission. Two distinct glutamate transporters, glutamate-aspartate transporter (GLAST) and excitatory amino acid transporter 4 (EAAT4), are expressed most abundantly in the molecular layer of the cerebellar cortex. GLAST is expressed in Bergmann glial processes surrounding excitatory synapses on Purkinje cell dendritic spines, whereas EAAT4 is concentrated on the extrasynaptic regions of Purkinje cell spine membranes. To clarify the functional significance of the coexistence of these transporters, we analyzed the kinetics of EPSCs in Purkinje cells of mice lacking either GLAST or EAAT4. There was no difference in the amplitude or the kinetics of the rising and initial decay phase of EPSCs evoked by stimulations of climbing fibers and parallel fibers between wild-type and EAAT4-deficient mice. However, long-lasting tail currents of the EPSCs appeared age dependently in most of Purkinje cells in EAAT4-deficient mice. These tail currents were never seen in mice lacking GLAST. In the GLAST-deficient mice, however, the application of cyclothiazide that reduces desensitization of AMPA receptors increased the peak amplitude of the EPSC and prolonged its decay more markedly than in both wild-type and EAAT4-deficient mice. The results indicate that these transporters play differential roles in the removal of synaptically released glutamate. GLAST contributes mainly to uptake of glutamate that floods out of the synaptic cleft at early times after transmitter release. In contrast, the main role of EAAT4 is to remove low concentrations of glutamate that escape from the uptake by glial transporters at late times and thus prevents the transmitter from spilling over to neighboring synapses.

Original languageEnglish
Pages (from-to)8788-8793
Number of pages6
JournalJournal of Neuroscience
Volume25
Issue number38
DOIs
Publication statusPublished - 2005 Sep 21
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Purkinje Cells
Excitatory Amino Acid Transporter 4
Neuroglia
Synapses
Glutamic Acid
Tail
Dendritic Spines
Cerebellar Cortex
AMPA Receptors
Synaptic Transmission
Spine
Cell Membrane

Keywords

  • Bergmann glia
  • EAAT4
  • EPSC
  • GLAST
  • Glutamate transporters
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. / Takayasu, Yukihiro; Iino, Masae; Kakegawa, Wataru; Maeno, Hiroshi; Watase, Kei; Wada, Keiji; Yanagihara, Dai; Miyazaki, Taisuke; Komine, Okiru; Watanabe, Masahiko; Tanaka, Kohichi; Ozawa, Seiji.

In: Journal of Neuroscience, Vol. 25, No. 38, 21.09.2005, p. 8788-8793.

Research output: Contribution to journalArticle

Takayasu, Y, Iino, M, Kakegawa, W, Maeno, H, Watase, K, Wada, K, Yanagihara, D, Miyazaki, T, Komine, O, Watanabe, M, Tanaka, K & Ozawa, S 2005, 'Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses', Journal of Neuroscience, vol. 25, no. 38, pp. 8788-8793. https://doi.org/10.1523/JNEUROSCI.1020-05.2005
Takayasu, Yukihiro ; Iino, Masae ; Kakegawa, Wataru ; Maeno, Hiroshi ; Watase, Kei ; Wada, Keiji ; Yanagihara, Dai ; Miyazaki, Taisuke ; Komine, Okiru ; Watanabe, Masahiko ; Tanaka, Kohichi ; Ozawa, Seiji. / Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 38. pp. 8788-8793.
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AU - Wada, Keiji

AU - Yanagihara, Dai

AU - Miyazaki, Taisuke

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