Modeling neuron-astrocyte interactions in neural networks using distributed simulation
Authors: Jiang Han-Jia , Aćimović Jugoslava , Manninen Tiina , Ahokainen Iiro , Stapmanns Jonas , Lehtimäki Mikko , Diesmann Markus , van Albada Sacha J. , Plesser Hans Ekkehard , Linne Marja-Leena 
Published: November 2024

AbstractAstrocytes 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 aims to enhance computational modeling of local interactions between neurons and astrocytes to better understand how these interactions influence the activity regimes in neuron-astrocyte networks and overall brain function. We develop new algorithms for representing astrocytes and neuron-astrocyte interactions in distributed simulation code for large-scale spiking neuronal networks. These include an astrocyte model with calcium dynamics, an extension of a standard neuron model to receive calcium-dependent signals from astrocytes, connections that deliver these signals to neurons, and a connectivity concept that efficiently establishes interactions between groups of three elements (pre- and postsynaptic neurons and astrocytes) in large neuron-astrocyte populations. The latter extends the conventional concept of binary connectivity in neuronal circuits. We verify the efficiency of our reference implementation through a series of benchmarks that vary in computing resources and neuron-astrocyte network model sizes. Using the new technology, we reproduce experimental data on astrocytic effects on neuronal synchronization. Ourin silicoexperiments demonstrate that astrocytes consistently induce local synchronization in groups of neurons across various connectivity schemes and global activity regimes. Changing only the efficiency of neuron-astrocyte interactions switches the global activity regime from asynchronous to network-wide synchronization. Our contribution supports reproducible and collaborative large-scale modeling projects of neuron-astrocyte circuits, addressing the growing interest in developing these models within the computational neuroscience community.Author summaryAstrocytes play an important role in regulating synapses, neuronal networks, and cognitive functions. However, models that include both neurons and astrocytes are underutilized compared to models with only neurons in theoretical and computational studies. We address this issue by developing concepts for the representation of astrocytic interaction and providing a reference implementation in the distributed spiking network simulation code NEST. Using these capabilities, we show how astrocytes help to synchronize neural networks under various connection patterns and activity levels. The new technology makes it easier to include astrocytes in simulations of neural systems, promoting the construction of more realistic, relevant and reproducible models.Data Availability StatementThe implemented astrocyte support is described in the user-level documentation of the NEST simulation code [1]. Benchmark code and the code for developing and simulating thein silicomodel are available athttps://zenodo.org/doi/10.5281/zenodo.13757203. The supporting information (S1 Appendix, S2 Appendix, and S3 Appendix) describe new variables and parameters of the NEST code, the specification of the network models used in this study, and the criteria for the choices of parameter values.FundingThis research has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreement No. 945539 (Human Brain Project SGA3) to SJvA and M-LL, from its Partnering Project (AstroNeuronNets) to JA and SJvA, from the European Union’s Horizon Europe Programme under the Specific Grant Agreement No. 101147319 (EBRAINS 2.0 Project) to SJvA and M-LL, from HiRSE PS, the Helmholtz Platform for Research Software Engineering - Preparatory Study, an innovation pool project of the Helmholtz Association, to SJvA, from Research Council of Finland, decision Nos. 326494, 326495, 345280, and 355256, to TM, and 297893 and 318879 to M-LL, and from The Käte Hamburger Kolleg: Cultures of Research (c:o/re) which is funded by the Federal Ministry of Education and Research under the funding code 01UK2104 to HEP. Open access publication funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491111487.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interestsThe authors have declared that no competing interests exist.