Magnetic stimulation and depression of mammalian networks in primary neuronal cell cultures

For transcranial magnetic stimulation (TMS), the coupling of induced electric fields with neurons in gray matter is not well understood. There is little information on optimal stimulation parameters and on basic cellular mechanisms. For this reason, magnetic stimulation of spontaneously active neuronal networks, grown on microelectrode arrays in culture, was employed as a test environment. This allowed use of smaller coils and the continual monitoring of network action potential (AP) activity before, during, and for long periods after stimulation. Biphasic, rectangular, and 500 micros long pulses were used at mean pulse frequencies (MPFs) ranging from 3 to 100 Hz on both spinal cord (SC) and frontal cortex (FC) cultures. Contrary to stimulation of organized fiber bundles, APs were not elicited directly. Responses were predominantly inhibitory, dose dependent, with onset times between 10 s and several minutes. Spinal networks showed a greater sensitivity to activity suppression. Under pharmacological disinhibition, some excitation was seen at low pulse frequencies. FC cultures showed greater excitatory responses than SC networks. The observed primary inhibitory responses imply interference with synaptic exocytosis mechanisms. With 20,000 pulses at 10 Hz, 40% inhibition was maintained for over 30 min with full recovery, suggesting possible application to nonchemical, noninvasive pain management.