An efficient stochastic diffusion algorithm for modeling second messengers in dendrites and spines.

Intracellular signaling pathways, which encompass both biochemical reactions and second messenger diffusion, interact non-linearly with neuronal membrane properties in their role as essential intermediaries for synaptic plasticity and neuromodulation. Computational modeling is a productive approach for investigating these phenomena; however, most current strategies for modeling neurons exclude signaling pathways. To overcome this deficiency, a new algorithm is presented to simulate stochastic diffusion in a highly efficient manner. The gain in speed is obtained by considering collections of molecules, instead of tracking the movement of individual molecules. The probability of a molecule leaving a spatially discrete compartment is used to create a lookup table that stores the probability of k(m) molecules leaving the compartment as a function of the total number of molecules in the compartment. During the simulation, the number of molecules leaving the compartment is determined using a uniform random number as an index into the lookup table. Simulations illustrate the accuracy of this algorithm by comparing it with the theoretical solution for deterministic diffusion. Additional simulations show how spines on a dendritic branch compartmentalize diffusible molecules. The efficiency of the algorithm is sufficient to allow simulation of second messenger pathways in a multitude of spines on an entire neuron.