Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices

To understand the elementary unit of synaptic communication between CNS neu rons, one must know what causes the variability of quantal postsynaptic cur rents and whether unitary packets of transmitter saturate postsynaptic rece ptors. We studied single excitatory synapses between hippocampal neurons in culture. Focal glutamate application at individual postsynaptic sites evok ed currents (I-glu) with little variability compared with quantal excitator y postsynaptic currents (EPSCs). The maximal I-glu was >2-fold larger than the median EPSC. Thus, variations in [glu](cleft) are the main source of va riability in EPSC size, and glutamate receptors are generally far from satu ration during quantal transmission. This conclusion was verified by molecul ar antagonism experiments in hippocampal cultures and slices. The general l ack of glutamate recepor saturation leaves room for increases in [glu](clef t) as a mechanism for synaptic plasticity.