Method of synaptic transmission hidden parameters evaluation based on inhibition analysis data

Abstract

Nowadays neuroscience strongly demands application of the mathematical methods for description of many neurophysiological and neurochemical processes among which the synaptic transmission outstands. One of the main problems in synaptic transmission modelling is the lack of the accurate values of dynamic parameters of biomolecules and complexes taking part in this process. The goal of this study is to elaborate the method for evaluation of synaptic transmission parameters that cannot be measured directly (so-called hidden parameters) and apply its results for investigation of the main stages of synaptic transmission in neuronets of hippocampus. The method is based on the parametric identification of the synaptic transmission deterministic model, which includes equations for description of inhibitors action on the main biochemical participants. We used three inhibitors: cilnidipine, 1.2-        bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The parametric identification was performed by minimization of deviation of modeled field excitatory postsynaptic potential from those measured in rat hippocampus slices with microelectrode technique when inhibitors were applied. The results of the parametric identification of proposed model show that the model can adequately describe the generation of field excitatory postsynaptic potentials and their inhibition. The elaborated method afforded to evaluate the numerical meanings of eleven synaptic transmission hidden parameters. Using these parameters we have modelled the key synaptic transmission stages and got the time courses of the main biochemical participants: calcium ions in presynaptic bouton, SNARE complexes, synaptic vesicles in different states, glutamate in the synaptic cleft and open channels of AMPA receptor on the postsynaptic membrane. Thus, we propose method of hidden parameters evaluation that can be applied for different synaptic contacts in the brain of mammalians.