Facilitated activation of metabotropic glutamate receptors in cerebellar Purkinje cells in glutamate transporter EAAT4-deficient mice.
Around excitatory synapses in cerebellar Purkinje cells (PCs), GLAST and EAAT4 are expressed as predominant glial and neuronal glutamate transporters, respectively. EAAC1, another subtype of neuronal glutamate transporter, is also expressed in PCs. EAAT4 is co-localized with metabotropic glutamate receptors (mGluRs) at perisynaptic sites in excitatory synapses in PCs, and this neuronal transporter was reported to be involved in the regulation of mGluR activation induced by the stimulation of parallel fibers (PFs). However, it remains to be elucidated whether only EAAT4 is specifically involved in mGluR activation among the glutamate transporters expressed near excitatory synapses in PCs. Here we examined mGluR-mediated excitatory postsynaptic currents (mGluR-EPSCs) evoked by PF stimulation in cerebellar slices of mice deficient in EAAT4, EAAC1, or GLAST. PF-evoked mGluR-EPSCs showed larger amplitude and faster rising kinetics in EAAT4-deficient mice than in the wild-type mice. In contrast, there was no significant difference in either the amplitude or the rising kinetics of mGluR-EPSCs in GLAST- or EAAC1-deficient mice compared to wild-type mice. We conclude that EAAT4 is most closely involved in mGluR activation in PCs among the glutamate transporters.
Nikkuni
Osamu
O
Department of Neurophysiology, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Takayasu
Yukihiro
Y
Iino
Masae
M
Tanaka
Kohichi
K
Ozawa
Seiji
S
D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism*; D004558:Electric Stimulation; D050581:Excitatory Amino Acid Transporter 4 / Q000235:genetics*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
D050581:Excitatory Amino Acid Transporter 4; D018094:Receptors, Metabotropic Glutamate; C493390:Slc1a6 protein, mouse; D018698:Glutamic Acid