Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude

In many neurons, responses to individual quanta of transmitter exhibit large variations in amplitude. The origin of this variability, although central to our understanding of synaptic transmission and plasticity, remains controversial. To examine the relationship between quantal amplitude and postsynaptic receptor number, we adopted a novel approach, combining patch-clamp recording of synaptic currents with quantitative immunogold localization of synaptic receptors. Here, we report that in cerebellar stellate cells, where variability in GABA miniature synaptic currents is particularly marked, the distribution of quantal amplitudes parallels that of synaptic GABA(A) receptor number. We also show that postsynaptic GABA(A) receptor density is uniform, allowing synaptic area to be used as a measure of relative receptor content. Flurazepam, which increases GABA(A) receptor affinity, prolongs the decay of all miniature currents but selectively increases the amplitude of large events. From this differential effect, we show that a quantum of GABA saturates postsynaptic receptors when <80 receptors are present but results in incomplete occupancy at larger synapses.