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The Journal of Neuroscience, December 15, 2001, 21(24):9638-9654
Estimating Transmitter Release Rates from Postsynaptic Current Fluctuations
Erwin Neher and Takeshi Sakaba Max Planck Institute for Biophysical Chemistry, Department of Membrane Biophysics, D-37077 Göttingen, Germany
A method is presented that allows one to estimate transmitter release rates from fluctuations of postsynaptic current records under conditions of stationary or slowly varying release. For experimental applications, we used the calyx of Held, a glutamatergic synapse, in which "residual current," i.e., current attributable to residual glutamate in the synaptic cleft, is present. For a characterization of synaptic transmission, several postsynaptic parameters, such as the mean amplitude of the miniature postsynaptic current and an apparent single channel conductance, have to be known. These were obtained by evaluating variance and two more higher moments of the current fluctuations. In agreement with Fesce et al. (1986), we found both by simulations and by analyzing experimental records that high-pass filtering of postsynaptic currents renders the estimates remarkably tolerant against nonstationarities. We also found that release rates and postsynaptic parameters can be reliably obtained when release rates are low (~10 events/msec). Furthermore, during a long-lasting stimulus, the transmitter release at the calyx of Held was found to decay to a low, stationary rate of 10 events/msec after depletion of the "releasable pool" of synaptic vesicles. This stationary release rate is compatible with the expected rate of recruitment of new vesicles to the release-ready pool of vesicles. MiniatureEPSC (mEPSC) size is estimated to be similar to the value of spontaneously occurring mEPSC under this condition.
Key words: synaptic transmission; exocytosis; noise analysis; skewness; cumulants; calyx of Held; vesicle pool
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249638-17$05.00/0
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