The volterra functional series is a viable alternative to kinetic models for synaptic modeling--calibration and benchmarking.

Abstract

Synaptic transmission is governed by a series of complex and highly nonlinear mechanisms and pathways in which the dynamics have a profound influence on the overall signal sent to the postsynaptic cell. In simulation, these mechanisms are often represented through kinetic models governed by state variables and rate law equations. Calculations of such ordinary differential equations (ODEs) in kinetic models can be computationally intensive, and although algorithms have been optimally developed to handle ODEs efficiently, simulation of numerous, large and complex kinetic models requires a prohibitively large amount of computational power. Here we present an alternative representation of ionotropic glutamatergic receptors AMPAr and NMDAr kinetic models consisting of input-output surrogates of the receptor models which can capture the nonlinear dynamics seen in the kinetic models. We benchmark this Input-Output (IO) synapse model and compare it with kinetic receptor models to evaluate the simulation time required when using either synapse model, as well as the number of time steps each model needs for simulation. While remaining faithful to the original dynamics of the model, our results indicate that the IO synapse model requires less simulation time than the kinetic models under conditions which elicit normal physiological responses, thereby improving computational efficiency while preserving the complex non-linear dynamics of the receptors. These IO surrogates therefore constitute an appealing alternative to kinetic models in large scale networks simulations.