Mathematical modelling of non-stationary fluctuation analysis for studyingchannel properties of synaptic AMPA receptors

1. The molecular properties of synaptic alpha -amino-3-hydroxy-5-methyl-4-i soxazolepropionate (AMPA) receptors are an important factor determining exc itatory synaptic transmission in the brain. Changes in the number (N) or si ngle-channel conductance (gamma) of functional AMPA receptors may underlie synaptic plasticity, such as long-term potentiation (LTP) and long-term dep ression (LTD). These parameters have been estimated using non-stationary fl uctuation analysis (NSFA). 2. The validity of NSFA for studying the channel properties of synaptic AMP A receptors was assessed using a cable model with dendritic spines and a mi croscopic kinetic description of AMPA receptors. Electrotonic, geometric an d kinetic parameters were altered in order to determine their effects on es timates of the underlying gamma. 3. Estimates of gamma were very sensitive to the access resistance of the r ecording (R-A) and the mean open time of AMPA channels. Estimates of gamma were less sensitive to the distance between the electrode and the synaptic site, the electrotonic, properties of dendritic structures, recording elect rode capacitance and background noise. Estimates of gamma were insensitive to changes in spine morphology, synaptic glutamate concentration and the pe ak open probability (P-o) of AMPA receptors. 4. The results obtained using the model agree with biological data, obtaine d from 91 dendritic recordings from rat CA1 pyramidal cells. A correlation analysis showed that R-A resulted in a slowing of the decay time constant o f excitatory postsynaptic currents (EPSCS) by approximately 150%, from an e stimated value of 3.1 ms. R-A also greatly attenuated the absolute estimate of gamma by approximately 50-70%. 5. When other parameters remain constant, the model demonstrates that NSFA of dendritic recordings can readily discriminate between changes in gamma v s. changes in Nor P-o. Neither background noise nor asynchronous activation of multiple synapses prevented reliable discrimination between changes in gamma and changes in either Nor P-o. 6. The model (available online) can be used to predict how changes in the d ifferent properties of AMPA receptors may influence synaptic transmission a nd plasticity.