Abstract

In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a “learning signal” to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity), and the modeling strategy may be extended to coordination among remote neuron clusters.

Highlights

  • For many years, astrocytes, a subgroup of glial cells found in the brain, have been thought to support neurons by providing them with vital elements needed for their survival [1,2,3]

  • Initial simulations provide insight into the valid range of synaptic input frequencies that cause Ca2+ oscillation in each of the Amplitude Modulation (AM), Frequency Modulation (FM) and AM-FM modes. This is followed by an investigation into the role of extrasynaptic NMDARs in providing a remote supervisory learning signal

  • Given that glutamate released by astrocytes can activate synchronized slow inward current (SIC) in neighboring synapses thereby acting as a bridging mechanism between circuits which are not directly coupled [97,98], we investigate dynamic coordination using the network in Figure 9 where each of the neighboring neurons N1 and N2 has four tripartite synapses

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Summary

Introduction

Astrocytes, a subgroup of glial cells found in the brain, have been thought to support neurons by providing them with vital elements needed for their survival [1,2,3]. The interaction of glutamate with astrocytic receptors leads to transient elevation in astrocytic intracellular Ca2+ levels [6,7,8,9], which represent a fundamental mode of excitation in astrocytes. In response to these Ca2+ transients, astrocytes release gliotransmitters which in turn modulate synaptic transmission by acting both on pre- and post-synaptic receptors. As well as intracellular communication, astrocytes communicate with each other through the propagation of Ca2+ waves, a process which is thought to be mediated via extracellular ATP diffusion and the transmission of inosotil 1, 4, 5-trisphosphate (IP3) through gap junctions. The exact nature of this process is still unclear [10,11,12,13,14]

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