Variability of excitatory currents due to single-channel noise, receptor number and morphological heterogeneity

Patch clamp recordings of excitatory postsynaptic currents (EPSCs) in central neurons reveal large fluctuations in amplitudes and decay times of AMPA-receptor-mediated EPSCs. By using Monte Carlo simulations of synaptic transmission in brainstem interneurons, we tested several hypothesis that could account for the observed variability. The coefficient of variation (CV) of 0.5 for miniature amplitudes cannot be explained by fluctuations in vesicle content or receptor distribution, but is traced to variations in receptor number, which is estimated as 77+/-39 receptors per bouton. As the variability of rise times reflects fluctuations in size of the post-synaptic density and heterogeneity of the receptor distribution, the relatively small CV=0.37 of experimentally determined values points to a homogeneous arrangement of receptors. Within our model the large variability of decay times (CV=0.49) can only be explained by fluctuations in the transmitter time course (mean residence times of 0.4+/-0.13 ms), presumably resulting from heterogeneities in synaptic morphology. Hence, our simulations indicate that different noise sources control the variability of amplitudes, rise and decay times. In particular, the distribution of decay times yields information about the synaptic transmission process, which cannot be obtained from other observables.