Excitatory effect of biphasic kHz field stimulation on CA1 pyramidal neurons in slices

BackgroundElectrical stimulation in the kilohertz-frequency range has been successfully used for treatment of various neurological disorders. Nevertheless, the mechanisms underlying this stimulation are poorly understood. ObjectiveTo study the effect of kilohertz-frequency electric fields on neuronal membrane biophysics we developed a reliable experimental method to measure responses of single neurons to kilohertz field stimulation in brain slice preparations. MethodsIn the submerged brain slice pyramidal neurons of the CA1 subfield were recorded in the whole-cell configuration before, during and after stimulation with an external electric field at 2kHz, 5kHz or 10 kHz. ResultsReproducible excitatory changes in rheobase and spontaneous firing were elicited during kHz-field application at all stimulating frequencies. The rheobase only decreased and spontaneous firing either was initiated in silent neurons or became more intense in previously spontaneously active neurons. Response thresholds were higher at higher frequencies. Blockade of glutamatergic synaptic transmission did not alter the magnitude of responses. Inhibitory synaptic input was not changed by kilohertz field stimulation. ConclusionkHz-frequency current applied in brain tissue has an excitatory effect on pyramidal neurons during stimulation. This effect is more prominent and occurs at a lower stimulus intensity at a frequency of 2kHz as compared to 5kHz and 10kHz.