Increases in Effective Cleft Glutamate Concentration During Expression of LTP

ABSTRACT

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is often associated with increases in quantal size, traditionally attributed to enhanced availability or efficacy of postsynaptic glutamate receptors. However, augmented quantal size might also reflect increases in neurotransmitter concentration within the synaptic cleft since AMPA-type glutamate receptors are not generally saturated during basal transmission. Here we report evidence that peak cleft glutamate concentration ([glu]cleft) increases during LTP, as indicated by a lessening of the blocking effects of rapidly unbinding antagonists of AMPA. The efficacy of slowly equilibrating antagonists remained unchanged. The elevated [glu]cleft helps support the increased quantal amplitude of AMPA-type EPSCs (excitatory postsynaptic currents) during LTP.