Induced current pharmacological split stimulation system for neuronal networks.

Magnetic stimulation noninvasively modulates neuronal activity through a magnetically induced current. However, despite the usefulness and popularity of this method, the effects of neuronal activity in the nonstimulated regions on the stimulus responses are unknown. Here, we report that the induced current-evoked responses were affected by neuronal activities in the nonstimulated regions. Our experiment used a Mu-metal-based localized induced current stimulation (LICS) system combined with the microfabricated cell culture chamber system and a microelectrode array (MEA). The cell culture chamber system has radiating microtunnels connecting one central and eight outer chambers, which were fabricated using soft lithography and a replica modeling technique with SU-8 photoresist and polydimethylsiloxane (PDMS). Rat cortical neurons were separately cultured in the chambers and formed functional synaptic connections through the microtunnels. By applying a biphasic alternating pulsed magnetic field to the Mu-metal located in the central chamber, induced currents were mainly generated near the cultured neurons and modified the neuronal activities, which were recorded through MEA. Furthermore, we confirmed that the evoked responses were modified by localized pharmacological stimulation (LPS) in the outer chambers. These results suggest that our system would be promising tool for analyzing the effect of magnetic stimulation on interacting neuronal activity.