Neurotransmitter homeostasis in and around synapses involves random processes such as diffusion, molecular binding and unbinding. A three-dimensional stochastic diffusion model of a synapse was developed to provide molecular level details of neurotransmitter homeostasis not predicted by alternative models based on continuum approaches. This framework was used to estimate effective diffusion and provide a more accurate prediction of geometric tortuosity in the perisynaptic region. The stochastic model was used to predict the relative contributions of non-synaptic sources to extracellular concentration in control, natural reward seeking, and chronic cocaine cases; and estimation of molecular influx rates required to maintain tone on presynaptic autoreceptors. Also, this was the first stochastic model to confirm the prediction of down-regulation of glutamate transporters by 40% after chronic cocaine. The model can be further generalized to study the role of diffusion path length in supporting neurotransmitter gradients and isolating the synapse.

This content is only available via PDF.
You do not currently have access to this content.