A Computational Model of Interactions Between Neuronal and Astrocytic Networks: The Role of Astrocytes in the Stability of the Neuronal Firing Rate.

Kerstin Lenk,Eero Satuvuori,Jules Lallouette,Hugues Berry,Jari A K Hyttinen,Antonio Ladrón-De-Guevara

doi:10.3389/fncom.2019.00092

Abstract

Recent research in neuroscience indicates the importance of tripartite synapses and gliotransmission mediated by astrocytes in neuronal system modulation. Although the astrocyte and neuronal network functions are interrelated, they are fundamentally different in their signaling patterns and, possibly, the time scales at which they operate. However, the exact nature of gliotransmission and the effect of the tripartite synapse function at the network level are currently elusive. In this paper, we propose a computational model of interactions between an astrocyte network and a neuron network, starting from tripartite synapses and spanning to a joint network level. Our model focuses on a two-dimensional setup emulating a mixed in vitro neuron-astrocyte cell culture. The model depicts astrocyte-released gliotransmitters exerting opposing effects on the neurons: increasing the release probability of the presynaptic neuron while hyperpolarizing the post-synaptic one at a longer time scale. We simulated the joint networks with various levels of astrocyte contributions and neuronal activity levels. Our results indicate that astrocytes prolong the burst duration of neurons, while restricting hyperactivity. Thus, in our model, the effect of astrocytes is homeostatic; the firing rate of the network stabilizes to an intermediate level independently of neuronal base activity. Our computational model highlights the plausible roles of astrocytes in interconnected astrocytic and neuronal networks. Our simulations support recent findings in neurons and astrocytes in vivo and in vitro suggesting that astrocytic networks provide a modulatory role in the bursting of the neuronal network.

Highlights

Neuroscience research has focused for long on neurons and their interacting networks
The internal calcium pathways may be linked to the release by the astrocyte of so-called gliotransmitters—like glutamate, D-serine, adenosine triphosphate (ATP), and GABA (γ-aminobutyric acid)—that influence the activity of the contacted neurons (Pasti et al, 2001; Henneberger et al, 2010; Zorec et al, 2012; Araque et al, 2014; Sahlender et al, 2014)
We develop a mathematical model of combined astrocyte-neuron networks to study the role of astrocyte networks on the modulation of the neuronal firing rate

Summary

Introduction

Neuroscience research has focused for long on neurons and their interacting networks. Intracellular calcium (Ca2+) transients are a prominent readout signal of astrocyte activity, and happens at different time scales (Kastanenka et al, 2019). They may be triggered by neuronal activity (Di Castro et al, 2011; Dallérac et al, 2013). The released IP3 binds to IP3- and Ca2+-gated Ca2+ channels in the membrane of the endoplasmic reticulum, leading to a Ca2+ elevation in the astrocyte cytosol These transient changes in the level of free cytoplasmic Ca2+ lead to the opening of further IP3 channels in a Ca2+-induced Ca2+ release (CICR) mechanism that further amplifies Ca2+ release from the endoplasmic reticulum. The internal calcium pathways may be linked to the release by the astrocyte of so-called gliotransmitters—like glutamate, D-serine, adenosine triphosphate (ATP), and GABA (γ-aminobutyric acid)—that influence the activity of the contacted neurons (Pasti et al, 2001; Henneberger et al, 2010; Zorec et al, 2012; Araque et al, 2014; Sahlender et al, 2014)

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