Modeling neuron-astrocyte interactions in neural networks using distributed simulation

PLoS Computational Biology, vol. 21, pp. e1013503

Abstract

Astrocytes engage in local interactions with neurons, synapses, other glial cell types, and the vasculature through intricate cellular and molecular processes, playing an important role in brain information processing, plasticity, cognition, and behavior. This study advances understanding of local interactions and self-organization of neuron-astrocyte networks and contributes to the broader investigation of their potential relationship with global activity regimes and overall brain function. We present six new contributions: (1) the development of a new model-building framework for neuron-astrocyte networks, (2) the introduction of connectivity concepts for tripartite neuron-astrocyte interactions in biological neural networks, (3) the design of a scalable architecture capable of simulating networks with up to a million cells, (4) a formalized description of neuron-astrocyte modeling that facilitates reproducibility, (5) the integration of experimental data to a greater extent than existing studies, and (6) simulation results demonstrating how neuron-astrocyte interactions drive the emergence of synchronization in local neuronal groups. Specifically, we develop a new technology for representing astrocytes and their interactions with neurons in distributed simulation code for large-scale spiking neuronal networks. This includes an astrocyte model with calcium dynamics, an extended neuron model receiving calcium-dependent signals from astrocytes, and a parallelized connectivity generation scheme for tripartite interactions between pre- and postsynaptic neurons and astrocytes. We verify the efficiency of our reference implementation through benchmarks varying in computing resources and network sizes. Our in silico experiments reproduce experimental data on astrocytic effects on neuronal synchronization, demonstrating that astrocytes consistently induce local synchronization in groups of neurons across various connectivity schemes and global activity regimes. By adjusting the strength of neuron-astrocyte interactions, we can switch the global activity regime from asynchronous to network-wide synchronization. This work represents an advancement in neuron-astrocyte modeling, introducing a novel framework that enables large-scale simulations of astrocytic influence on neuronal networks.

Authors 10

1. Han-Jia Jiang corresponding

   Forschungszentrum Jülich · University of Cologne

   Affiliation as printed

   Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany

   Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany

2. Jugoslava Aćimović corresponding

   Tampere University · University of Tampere

   Affiliation as printed

   Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

3. Tiina Manninen

   Tampere University · University of Tampere

   Affiliation as printed

   Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

4. Iiro Ahokainen

   Tampere University · University of Tampere

   Affiliation as printed

   Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

5. Jonas Stapmanns Aachen Department of Physics Faculty 1

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Department of Physics, Faculty 1, RWTH Aachen University, Aachen, Germany

   Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany

6. Mikko Lehtimäki

   Tampere University · University of Tampere

   Affiliation as printed

   Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

7. Markus Diesmann Aachen Department of Physics Faculty 1 Department of Psychiatry, Psychotherapy and Psychosomatics School of Medicine

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Department of Physics, Faculty 1, RWTH Aachen University, Aachen, Germany

   Department of Psychiatry, Psychotherapy and Psychosomatics, School of Medicine, RWTH Aachen University, Aachen, Germany

   Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany

8. Sacha Jennifer van Albada

   Forschungszentrum Jülich · University of Cologne

   Affiliation as printed

   Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany

   Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany

9. Hans Ekkehard Pleßer Aachen Käte Hamburger Kolleg "Cultures of Research" (Core)

   Forschungszentrum Jülich · Norwegian University of Life Sciences · RWTH Aachen University

   Affiliation as printed

   Department of Data Science, Faculty of Science and Technology, Norwegian University of Life Sciences, Ås, Norway

   Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany

   Käte Hamburger Kolleg: Cultures of Research (c:o/re), RWTH Aachen University, Aachen, Germany

10. Marja‐Leena Linne corresponding

    Tampere University · University of Tampere

    Affiliation as printed

    Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland