Abstract
Biological neural networks exhibit synchronized activity within and across interconnected regions of the central nervous system. Understanding how these coordinated networks are established and maintained may reveal therapeutic targets for neurodegeneration and neuromodulation. Here, we tested the influence of astrocytes upon synchronous network activity using human pluripotent stem cell-derived bioengineered neural organoids. This study revealed that astrocytes significantly increase activity within individual organoids and across long distances among numerous rapidly merged organoids via influencing synapses and bioenergetics. Treatment of amyloid protein inhibited synchronous activity during neurodegeneration, yet this can be rescued by propagating activity from neighboring networks. Altogether, this study identifies critical contributions of human astrocytes to biological neural networks and delivers a rapid, reproducible, and scalable model to investigate long-range functional communication of the nervous system in healthy and disease states.