Modulation of neuronal network activity using magnetic nanoparticle-based astrocytic network integration

Investigating the mechanisms of the neuron–glia interaction is important in the basic research of neuroscience and neural transplantation. Synaptic transmission is modulated by astrocyte activation in the pre- and post-synaptic terminals, and this phenomenon is spread to the surrounding astrocytes through gap junctions. However, the modulation of network-wide neuronal activity dependent on extensive astrocyte activation is not well understood. In this study, we show network-wide neuronal modulation associated with a newly developed three-dimensional neuronal and astrocytic network co-culture method. To establish widespread neuronal and astrocytic network interactions in vitro, we performed integration of magnetic nanoparticle-injected astrocytes (Mag-AS) onto the matured monolayer of neuronal networks using an external magnetic force. The neuronal electrical activity was dynamically synchronized at 24 h after integration of the Mag-AS network. In addition, Mag-AS network activation using a caged calcium compound rapidly induced suppression and subsequent synchronization of neuronal electrical activity. These results indicate that the high-density astrocytic network integration onto the neuronal network can induce widespread neuronal modulation, and our in vitro co-culture method contributes to the advancement of neuronal and astrocytic transplantation research.