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Volume 17, Number 21,
Issue of November 1, 1997
pp. 8137-8146
Copyright ©1997 Society for Neuroscience
Presynaptic Depression at a Calyx Synapse: The Small Contribution
of Metabotropic Glutamate Receptors
Received June 26, 1997; revised Aug. 8, 1997; accepted Aug. 12, 1997.
Henrique von Gersdorff,
Ralf Schneggenburger,
Sibylle Weis, and
Erwin Neher
Department of Membrane Biophysics, Max Planck Institute for
Biophysical Chemistry, D-37077 Göttingen, Germany
Synaptic depression of evoked EPSCs was quantified with stimulation
frequencies ranging from 0.2 to 100 Hz at the single CNS synapse formed
by the calyx of Held in the rat brainstem. Half-maximal depression
occurred at 1 Hz, with 10 and 100 Hz stimulation frequencies reducing EPSC amplitudes to 30% and 10% of their initial
magnitude, respectively. The time constant of recovery from depression
elicited by 10 Hz afferent fiber stimulation was 4.2 sec. AMPA and NMDA receptor-mediated EPSCs depressed in parallel at 1-5 Hz stimulation frequencies, suggesting that depression was induced by presynaptic mechanism(s) that reduced glutamate release. To determine the contribution of autoreceptors to depression, we studied the inhibitory effects of the metabotropic glutamate receptor (mGluR) agonists (1S, 3S)-ACPD and L-AP4 and
found them to be reversed in a dose-dependent manner by
(RS)- -cyclopropyl-4-phosphonophenylglycine (CPPG), a
novel and potent competitive antagonist of mGluRs. At 300 µM, CPPG completely reversed the effects of
L-AP4 and (1S, 3S)-ACPD, but
reduced 5-10 Hz elicited depression by only 6%. CPPG-sensitive mGluRs, presumably activated by glutamate spillover during
physiological synaptic transmission, thus contribute on the order of
only 10% to short-term synaptic depression. We therefore suggest that
the main mechanism contributing to the robust depression elicited by
5-10 Hz afferent fiber stimulation of the calyx of Held synapse is
synaptic vesicle pool depletion.
Key words:
EPSCs;
NMDA;
AMPA;
competitive antagonist;
synaptic
transmission;
auditory brainstem slices;
secretion;
short-term
plasticity
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