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Spontaneous and evoked excitatory postsynaptic currents (EPSCs) were recorded in slices of the rat anteroventral cochlear nucleus (AVCN) at the endbulb-bushy cell synaptic connection. 2. The amplitudes of alpha-amino-3-hydroxy-5-methy-4-isoxa-zolepropionic acid (AMPA)-receptor-mediated spontaneous EPSCs were large (54 +/- 6 pA, mean +/- SD; membrane potential = -70 mV, 22-25 degrees C) and, in the same cell, exhibited a very wide range of peak amplitudes (CM = 0.42 +/- 0.01, n - 15 cells). There was no significant correlation between rise times or decay time constants and the peak amplitudes of spontaneous EPSCs recorded in the same cell, demonstrating that electrotonic attenuation is not responsible for the large amplitude variability of spontaneous EPSCs. 3. Cyclothiazide, a potent blocker of AMPA-receptor desensitization, did not affect the amplitude of spontaneous EPSCs in AVCN bushy cells, suggesting that background desensitization of AMPA receptors is not significant in these cells. However, the decay time constant of spontaneous EPSCs was prolonged significantly (2.6-fold increase). In addition, cyclothiazide produced a marked increase (approximately 40%, n = 6 cells) in the frequency of spontaneous EPSCs, indicating a likely presynaptic site of action of this drug. 4. Cyclothiazide produced a small increase (approximately 10%, n = 7 cells) in the peak amplitude of the evoked endbulb EPSC, but this effect could be explained by the action of cyclothiazide to increase the decay time constant of the underlying quantal EPSCs in conjunction with the asynchrony of quantal transmitter release at the endbulb synapse. 5. These results indicate that neither electrotonic attenuation nor receptor desensitization are responsible for the wide range of peak amplitudes of spontaneous EPSCs in bushy cells. The large quantal variability therefore is likely to be due entirely to intrinsic fluctuations at each release site and site-to-site variability in the numbers of available receptors.
Isaacson et al. (Sun,) studied this question.