Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons. Maki, Reiko, Dana D. Cummings, and Marc A. Dichter. David Mahoney Institute of Neurological Sciences, University of Pennsylvania, School of Medicine, Departments of Neurology and Pharmacology, University of Pennsylvania, School of Medicine, and The Graduate Hospital, Philadelphia, PA, 19104.
APStracts 2:0178N, 1995.
SUMMARY AND CONCLUSIONS
1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse, were used to investigate the possible role of presynaptic metabotropic glutamate receptors (mGluRs) in frequency-dependent modulation of the amplitude of excitatory postsynaptic currents (EPSCs). Paired whole-cell patch clamp recordings from monosynaptically connected hippocampal neurons maintained in very low density cultures were performed, using the mGluR antagonist (RS)-a-methyl-4-carboxyphenylglycine (MCPG, 500 M) and mGluR agonist (1S, 3R)-1- aminocyclopentane-1,3-dicarboxylic acid ((1S, 3R)-ACPD, 100 M). 2. Paired-pulse depression (PPD) was observed in all the excitatory pairs recorded. The average PPD ratio (amplitude of the second EPSC divided by the amplitude of the first EPSC) was 0.80 0.1 (n=8). Application of the mGluR antagonist MCPG had no effect on the amplitude of the EPSCs, and did not affect the ratio of the two PSCs (PPD ratio 0.79 0.2). 3. The amplitudes of ten successive EPSCs stimulated at a high-frequency (20 Hz) decremented on average in both 4 mM extracellular Ca2+ (n=5)and in 1 mM extracellular Ca2+ (n=6). In all pairs tested, post-tetanic depression (PTD) was observed (PTD ratio 0.7 0.2). Bath application of MCPG (500 M) did not affect the amplitudes of the EPSCs during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S, 3R)-ACPD depressed the amplitudes of the EPSCs in both the paired-pulse (35 9% EPSC I; 36 10% EPSC II) and post-tetanic pulse (1 and 4 mM extracellular Ca2+ ) paradigms. The amount of depression observed, both PPD and PTD, remained unaffected by application of (1S, 3R)-ACPD. Coapplication of the antagonist MCPG (500 µM) blocked the effects of (1S, 3R)- ACPD (100 M). 5. We conclude that frequency-dependent depression of EPSC amplitudes occurs independent of endogenous activation of MCPG-sensitive metabotropic glutamate receptors in cultured hippocampal neurons. Moreover, we have demonstrated that exogenous activation of mGluRs by the agonist (1S, 3R)- ACPD can produce additional EPSC depression above that already present due to frequency-dependent mechanisms. 

Received 23 December 1994; accepted in final form 15 May 1995.
APS Manuscript Number J806-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.