Realizing Synaptic Signal Transmission During Astrocyte-Neuron Interactions within the EMI Framework

AbstractThe tripartite synapse or “neural threesome” refers to the interplay in the synapse between neighbouring neurons, the synaptic cleft, and the surrounding glial cells. Despite extensive research, the effects of glial cells, such as astrocytes, on signal transduction between neurons are not fully understood. The Kirchhoff-Nernst- Planck (KNP) and Extracellular-Membrane-Intracellular (EMI) models constitute a promising framework for modeling these kinds of systems. However, they lack the neurotransmitter-related mechanisms that are necessary to bridge signal transduction across the synaptic cleft. Here, we propose an extension to the KNP-EMI model by a spatio-temporal diffusion-based description of the most prominent neurotransmitter, glutamate, that allows for investigation of the contribution of astrocytes to the functionality of the synapse. We validate our model by showing that the presence of an astrocyte in the domain affects the glutamate flux across the postsynaptic terminal, as observed physiologically. The proposed extension offers a sufficiently simple way of integrating synaptic glutamate dynamics into the KNP-EMI framework. It introduces the relevant interactions between electrical activity and diffusion processes at the tripartite synapse that are necessary to assess how astrocytes might contribute to the functionality of the synapse. This work has implications for future studies involving glial mechanisms and other charged species within the KNP-EMI framework.