Cellular Mechanisms Underlying State-Dependent Neural Inhibition with Magnetic Stimulation

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity in a state-dependent manner. It inhibited neurons in slow-firing states, but spared neurons from fast-firing states, when the same magnetic stimuli were applied. Using a multi-compartment NEURON model, we found that dynamics of voltage-dependent sodium and potassium channels were significantly altered by the magnetic stimulation in the slow-firing neurons, but not in the fast-firing neurons. Variability in neural activity should be monitored and explored to optimize the outcome of magnetic stimulation in basic laboratory research and clinical practice. If selective stimulation can be programmed to match the appropriate neural state, prosthetic implants and brain-machine interfaces can be designed based on these concepts to achieve optimal results

Activity-Dependent Neuronal Cell Migration Induced by Electrical Stimulation

Recently, we found that electrical stimulation can induce neuronal migration in neural networks cultured for more than 3 weeks on microelectrode arrays. Immunocytochemistry data showed that the aggregation of neurons was related to the emergence of astrocytes in culture. In this study, when neurons were cocultured with astrocytes, electrical stimulation could induce the migration of neuronal cell bodies after only 1 week in culture, while the same stimulation paradigm caused neural necrosis in neuron-only cultures. In addition, the stimulation-induced migration was inhibited by blocking action potentials in neural networks using the voltage-gated sodium channel blocker, tetrodotoxin. Immunocytochemistry was performed to monitor precisely the neuronal migration and count the number of neurons. These results indicate that neuronal migration of cell bodies is dependent on neuronal activity evoked by electrical stimulation and can be enhanced by coculturing with astrocytes. We believe this method can be employed as a means for modifying neural networks and improving the interface between electrodes and neurons.This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Nano Bioelectronics and Systems Research Center [Grant No. R11-2000-075- 00002-0 for domestic research and R11- 330 2000-075-01001-0 for international collaboration (June)]