Modeling neuron-astrocyte interactions in neural networks using distributed simulation.

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.