ASYNCHRONOUS RELEASE OF SYNAPTIC VESICLES DETERMINES THE TIME-COURSE OF THE AMPA RECEPTOR-MEDIATED EPSC

The contribution of intersynaptic transmitter diffusion to the AMPA re ceptor EPSC time course was studied in cultured CA1 hippocampal neuron s. Reducing release probability 20-fold with cadmium did not affect th e time course of the averaged AMPA receptor EPSC, even when receptor d esensitization was blocked by cyclothiazide, suggesting that individua l synapses contribute independently to the AMPA receptor-mediated EPSC . Deconvolution of the averaged miniature EPSC from the evoked EPSC sh owed that release probability decays only slightly faster than the EPS C, suggesting that the AMPA receptor EPSC time course is determined pr imarily by the asynchrony of vesicle release. Further experiments demo nstrated that cyclothiazide, previously thought to affect only AMPA re ceptor kinetics, also enhances synaptic release.