Quantal variability at glutamatergic synapses in area CA1 of the rat neonatal hippocampus

1. Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal days 1-7) rat hippocampal slice preparation. Synaptic AMPA and NMDA quantal EPSCs were recorded from CA1. pyramidal neurones using the whole-cell, or perforated, patch-clamp technique. 2. Release was evoked by minimal stimulation using brief trains (10 impulses, 50 Hz), and various tests ascertained that this stimulation activated single release sites releasing single vesicles. 3. Both AMPA and NMDA quantal responses at a given release site varied considerably in magnitude, the coefficient of variation (CV) among the synapses averaging 0.39 and 0.30, respectively. This variability differed among the synapses, from 0.2 to 0.7, and 0.10 to 0.50, respectively, and CV values of AMPA responses co-varied with those of the NMDA responses. 4. Both for AMPA and NMDA, low CV values were associated with a Gaussian distribution of EPSC peak values, whereas synapses with high CV values displayed distributions skewed towards lower values. 5. Analysis of successive NMDA responses during a train revealed a considerable degree of nonsaturation of NMDA receptors by a single vesicle. 6. The results are compatible with a quantal variability based, to a large extent, on nonsaturated AMPA and NMDA responses fluctuating as a function of the amount of transmitter released from each vesicle.