Synaptic Channel Modeling for DMC: Neurotransmitter Uptake and Spillover in the Tripartite Synapse

TL;DR

This paper develops a detailed biophysical model of the tripartite synapse for diffusive molecular communication, deriving analytical expressions for the channel response and molecule uptake, validated by simulations and experiments.

Contribution

It introduces a comprehensive 3D synaptic channel model considering uptake and spillover, providing analytical tools for understanding synaptic communication in DMC systems.

Findings

Analytical expressions for the channel impulse response and molecule uptake rates.

Model validation through particle-based simulations and experimental data.

Insights into how physical parameters influence synaptic signal decay and reuptake.

Abstract

In Diffusive Molecular Communication (DMC), information is transmitted by diffusing molecules. Synaptic signaling, as a natural implementation of this paradigm, encompasses functional components that, once understood, can facilitate the development of synthetic DMC systems. To unleash this potential, however, a thorough understanding of the synaptic communication channel based on biophysical principles is needed. Since synaptic transmission critically depends also on non-neural cells, such understanding requires the consideration of the so-called tripartite synapse. In this paper, we develop a comprehensive channel model of the tripartite synapse encompassing a three-dimensional, finite-size spatial model of the synaptic cleft, molecule uptake at the presynaptic neuron and at glial cells, reversible binding to individual receptors at the postsynaptic neuron, and spillover to the extrasynaptic space. Based on this model, we derive analytical time domain expressions for the channel impulse response (CIR) of the synaptic DMC system and for the number of molecules taken up at the presynaptic neuron and at glial cells, respectively. These expressions provide insight into the impact of macroscopic physical channel parameters on the decay rate of the CIR and the reuptake rate, and reveal fundamental limits for synaptic signal transmission induced by chemical reaction kinetics and the channel geometry. Adapted to realistic parameters, our model produces plausible results when compared to experimental and simulation studies and we provide results from particle-based computer simulations to further validate the analytical model. The proposed comprehensive channel model admits a wide range of synaptic configurations making it suitable for the investigation of many practically relevant questions, such as the impact of glial cell uptake and spillover on signal transmission in the tripartite synapse.