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The Journal of Neurophysiology Vol. 87 No. 4 April 2002, pp. 1974-1980
Copyright ©2002 by the American Physiological Society
Laboratory for Neuronal Circuit Dynamics, Brain Science Institute, RIKEN, Saitama 351-0198, Japan
Reichelt, W. and
T. Knöpfel.
Glutamate Uptake Controls Expression of a Slow Postsynaptic
Current Mediated by mGluRs in Cerebellar Purkinje Cells. J. Neurophysiol. 87: 1974-1980, 2002. At the
cerebellar parallel fiber-Purkinje cell synapse, isolated presynaptic
activity induces fast excitatory postsynaptic currents via ionotropic
glutamate receptors while repetitive, high-frequency, presynaptic
activity can also induce a slow excitatory postsynaptic current that is
mediated by metabotropic glutamate receptors (mGluR1-EPSC). Here we
investigated the involvement of glutamate uptake in the expression of
the mGluR1-EPSC. Inhibitors of glutamate uptake led to a large increase
of the mGluR1-EPSC. D-aspartate (0.4 mM) and
L( These results show that expression of the slow mGluR-mediated
excitatory postsynaptic current is controlled by glutamate transporter activity. Thus in contrast to fast glutamatergic synaptic transmission, metabotropic glutamate receptor-mediated transmission is critically dependent on the activity and capacity of glutamate uptake.
)-threo-3-hydroxyaspartate (0.4 mM) increased the
mGluR1-EPSC ~4.5 and ~9-fold, respectively, while dihydrokainic
acid (1 mM), had no significant effect on the mGluR1-EPSC. D-aspartate (0.4 mM) shifted the concentration-response
curve of the depression of the mGluR1-EPSC by the low-affinity mGluR1 antagonist (S)-a-Methyl-4-carboxyphenylglycine
[(S)-MCPG] to higher concentrations and
decreased the stimulus intensity and the number of necessary stimuli to
evoke an mGluR1-EPSC. Depression of the mGluR1-EPSC by rapid pressure
application of (S)-MCPG at varying time intervals after
tetanic stimulation of the parallel fibers indicated that the glutamate
concentration in the peri- and extrasynaptic space decayed with time
constants of 36 and 316 ms under control conditions and with inhibition
of glutamate uptake, respectively.
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