Savtchenko L. Influence of spatial characteristics of synapses and postsynaptic structures on processes of neuronal excitation. Modeling study

Theoretical methods in combination with experimental approaches were used to study the role of sub-cellular structural organization in (1) neuronal excitability, (2) dynamics of intracellular calcium and (3) synaptic efficiency. It was found that generation of action potentials (APs) depends on the stochastic transitions of voltage-operated channels. The variability of AP latency is determined by the spatial density of sodium channels and by the rate of subthreshold depolarization. Clustering the channels or reducing their number increases this variability. Lateral electrodiffusion could be one mechanism that drives channel clustering. This in turn could depend on the electric field formed by the non-uniform distribution of intracellular calcium discharged from intracellular stores (each containing >104 ions). Channel clustering, together with the synap-tic cleft geometry, should also affect synaptic efficacy. Although larger synapses are likely to have higher release probabilities, they incur greaterlosses of the synaptic current in the cleft. An increase in the release probability can occur either by increasing the vesicular depot, or by enhancing positive electrical feedback between the presynaptic and postsynaptic cells.