Molecular Noise in Synaptic Communication.

Abstract

In synaptic molecular communication (MC), the activation of postsynaptic receptors by neurotransmitter (NTs) is governed by a stochastic reaction-diffusion process. This randomness of synaptic MC contributes to the randomness of the electrochemical downstream signal in the postsynaptic cell, called postsynaptic membrane potential (PSP). Since the randomness of the PSP is relevant for neural computation and learning, characterizing the statistics of the PSP is critical. However, the statistical characterization of the synaptic reaction-diffusion process is difficult because the reversible bi-molecular reaction of NTs with receptors renders the system nonlinear. Consequently, there is currently no model available which characterizes the impact of the statistics of postsynaptic receptor activation on the PSP. In this work, we propose a novel statistical model for the synaptic reaction-diffusion process in terms of the chemical master equation (CME). We further propose a novel numerical method which allows to compute the CME efficiently and we use this method to characterize the statistics of the PSP. Finally, we present results from stochastic particle-based computer simulations which validate the proposed models. We show that the biophysical parameters governing synaptic transmission shape the autocovariance of the receptor activation and, ultimately, the statistics of the PSP. Our results suggest that the processing of the synaptic signal by the postsynaptic cell effectively mitigates synaptic noise while the statistical characteristics of the synaptic signal are preserved. The results presented in this paper contribute to a better understanding of the impact of the randomness of synaptic signal transmission on neuronal information processing.