Monte Carlo Simulation of Neuro- Transmitter Release Using MCell, a General Simulator of Cellular Physiological Processes

Abstract

Issues surrounding synaptic current efficacy, variability, plasticity, and possible crosstalk are presently of great interest and lend themselves well to computational investigations. One important factor that impacts on all of these issues is the time course of neurotransmitter exocytosis from a synaptic vesicle.¹ We have recently reported excellent quantitative agreement between highly accurate recordings of the fast rising phase of miniature endplate currents (mEPCs), and Monte Carlo simulations of vesicular acetylcholine release and postsynaptic mEPC generation.² The simulations were performed using an early version of our program MCell, * a generalized and highly optimized outgrowth of our original Monte Carlo programs specifically tailored to simulation of mEPC generation.^3,4 In this paper we first briefly introduce the present version of MCell and its capabilities, and then next discuss simulation of neurotransmitter exocytosis. We focus on: (1) the theoretical and computational factors underlying simulation accuracy: (2) how inadvertent use of seemingly appropriate input parameters can lead to orders-of- magnitude errors; and (3) how some of MCell’s features can reduce the computation time required for simulations by orders of magnitude.