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Glial glutamate transporters maintain one-to-one relationship at the climbing fiber-Purkinje cell synapse by preventing glutamate spillover
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(24)
- Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Cerebellum
Phosphorylcholine
Purkinje cell
Glutamic Acid
AMPA receptor
Biology
In Vitro Techniques
Benzothiadiazines
Synapse
chemistry.chemical_compound
Mice
Purkinje Cells
Nerve Fibers
medicine
Excitatory Amino Acid Agonists
Animals
Excitatory Amino Acid Agonist
Mice, Knockout
Aspartic Acid
General Neuroscience
musculoskeletal, neural, and ocular physiology
Glutamate receptor
Excitatory Postsynaptic Potentials
Dose-Response Relationship, Radiation
Neural Inhibition
Glutamic acid
Climbing fiber
Articles
Electric Stimulation
Cell biology
Excitatory Amino Acid Transporter 1
Mice, Inbred C57BL
medicine.anatomical_structure
Biochemistry
chemistry
nervous system
Animals, Newborn
Synapses
Methacrylates
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 26
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....afa277fddc7de2abbee40c95cc654eab