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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 approx 1 Hz, with 10 and 100 Hz stimulation frequencies reducing EPSC amplitudes to approx 30% and approx 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)-alpha -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 approx 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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Science, July 21, 2000; 289(5478): 460 - 463.
[Abstract] [Full Text]


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S. Nawy
Regulation of the On Bipolar Cell mGluR6 Pathway by Ca2+
J. Neurosci., June 15, 2000; 20(12): 4471 - 4479.
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J. S. Diamond and C. E. Jahr
Synaptically Released Glutamate Does Not Overwhelm Transporters on Hippocampal Astrocytes During High-Frequency Stimulation
J Neurophysiol, May 1, 2000; 83(5): 2835 - 2843.
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R. Turecek and L. O. Trussell
Control of Synaptic Depression by Glutamate Transporters
J. Neurosci., March 1, 2000; 20(5): 2054 - 2063.
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J. S. Dittman, A. C. Kreitzer, and W. G. Regehr
Interplay between Facilitation, Depression, and Residual Calcium at Three Presynaptic Terminals
J. Neurosci., February 15, 2000; 20(4): 1374 - 1385.
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J G G Borst and B Sakmann
Depletion of calcium in the synaptic cleft of a calyx-type synapse in the rat brainstem
J. Physiol., November 15, 1999; 521(1): 123 - 133.
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C.-Y. Chen, J. M. Horowitz, and A. C. Bonham
A presynaptic mechanism contributes to depression of autonomic signal transmission in NTS
Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1350 - H1360.
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L.-G. Wu, R. E. Westenbroek, J. G. G. Borst, W. A. Catterall, and B. Sakmann
Calcium Channel Types with Distinct Presynaptic Localization Couple Differentially to Transmitter Release in Single Calyx-Type Synapses
J. Neurosci., January 15, 1999; 19(2): 726 - 736.
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M. F Cuttle, T. Tsujimoto, I. D Forsythe, and T. Takahashi
Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem
J. Physiol., November 1, 1998; 512(3): 723 - 729.
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J. S. Dittman and W. G. Regehr
Calcium Dependence and Recovery Kinetics of Presynaptic Depression at the Climbing Fiber to Purkinje Cell Synapse
J. Neurosci., August 15, 1998; 18(16): 6147 - 6162.
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R A. Silver, A. Momiyama, and S. G Cull-Candy
Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses
J. Physiol., August 1, 1998; 510(3): 881 - 902.
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T. Sakaba and E. Neher
Preferential potentiation of fast-releasing synaptic vesicles by cAMP at the calyx of Held
PNAS, January 2, 2001; 98(1): 331 - 336.
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Proc. Natl. Acad. Sci. USAHome page
O. Caillard, H. Moreno, B. Schwaller, I. Llano, M. R. Celio, and A. Marty
Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity
PNAS, November 21, 2000; 97(24): 13372 - 13377.
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L.-Y. Wang
The Dynamic Range for Gain Control of NMDA Receptor-Mediated Synaptic Transmission at a Single Synapse
J. Neurosci., December 15, 2000; 20(24): RC115 - RC115.
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C.-Y. Chen, E.-h. Ling, J. M Horowitz, and A. C Bonham
Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats
J. Physiol., February 1, 2002; 538(3): 773 - 786.
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I. Joshi and L.-Y. Wang
Developmental profiles of glutamate receptors and synaptic transmission at a single synapse in the mouse auditory brainstem
J. Physiol., May 1, 2002; 540(3): 861 - 873.
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