PRESYNAPTIC DEPRESSION AT A CALYX SYNAPSE - THE SMALL CONTRIBUTION OFMETABOTROPIC GLUTAMATE RECEPTORS

Synaptic depression of evoked EPSCs was quantified with stimulation fr equencies 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 occ urred at approximate to 1 Hz, with 10 and 100 Hz stimulation frequenci es reducing EPSC amplitudes to approximate to 30% and approximate to 1 0% of their initial magnitude, respectively. The time constant of reco very from depression elicited by 10 Hz afferent fiber stimulation was 4.2 sec. AMPA and NMDA receptor-mediated EPSCs depressed in parallel a t 1-5 Hz stimulation frequencies, suggesting that depression was induc ed by presynaptic mechanism(s) that reduced glutamate release. To dete rmine the contribution of autoreceptors to depression, we studied the inhibitory effects of the metabotropic glutamate receptor (mGluR) agon ists (1S, 3S)-ACPD and L-AP4 and found them to be reversed in a dose-d ependent manner by (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CP PG), a novel and potent competitive antagonist of mGluRs. At 300 mu M, CPPG completely reversed the effects of L-AP4 and (1S, 3S)-ACPD, but reduced 5-10 Hz elicited depression by only approximate to 6%. CPPG-se nsitive mGluRs, presumably activated by glutamate spillover during phy siological 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.