RT Journal Article SR Electronic T1 Presynaptic Depression at a Calyx Synapse: The Small Contribution of Metabotropic Glutamate Receptors JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8137 OP 8146 DO 10.1523/JNEUROSCI.17-21-08137.1997 VO 17 IS 21 A1 von Gersdorff, Henrique A1 Schneggenburger, Ralf A1 Weis, Sibylle A1 Neher, Erwin YR 1997 UL http://www.jneurosci.org/content/17/21/8137.abstract AB 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)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), a novel and potent competitive antagonist of mGluRs. At 300 μm, CPPG completely reversed the effects ofl-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.