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.