Abstract
Glutamate transporters are essential to remove synaptically released glutamate in excitatory synapses. Glial glutamate transporters expressed in Bergmann glia remove the majority of glutamate at excitatory synapses in cerebellar Purkinje cells (PCs) at early times after transmitter release. The neuronal glutamate transporter, the excitatory amino acid transporter 4 (EAAT4), is concentrated at perisynaptic sites of PCs, where metabotropic glutamate receptors (mGluRs) are located. To clarify the contribution of EAAT4 to the regulation of mGluR activation, we recorded mGluR-mediated excitatory postsynaptic currents (mGluR-EPSCs) in cerebellar slices of mice deficient in EAAT4 and compared them with those in wild-type (WT) mice. The amplitude of mGluR-EPSCs evoked by the stimulation of parallel fibers (PFs) was larger in EAAT4-deficient mice than that in WT mice. However, the amplitudes of PF-evoked mGluR-EPSCs in EAAT4-deficient and wild-type mice were similar in the presence of the glutamate transporter antagonist DL-threo-β-benzyloxyaspartic acid (TBOA). mGluR-EPSCs evoked by the stimulation of climbing fibers (CFs) were observed in EAAT4-deficient mice but not in WT mice in the normal saline. When the function of EAAT4 was inhibited by a pharmacological treatment, mGluR-EPSCs were elicited by the stimulation of CFs even in WT mice. These results indicate that EAAT4 plays a critical role in the regulation of the activation of perisynaptic mGluRs at both PF and CF synapses in PCs. [J Physiol Sci. 2006;56 Suppl:S164]
