Different Effects of Monophasic Pulses and Biphasic Pulses Applied by a Bipolar Stimulation Electrode in the Rat Hippocampal CA1 Region
Abstract Background: Deep brain stimulation (DBS) has been successfully used for treating certain brain diseases such as movement disorders. High-frequency stimulations (HFS) of charge-balanced biphasic pulses have been used in clinic DBS to minimize the risk of tissue damages caused by the electrical stimulations, while HFS sequences of monophasic pulses have been used in animal experiments to investigate DBS therapy. However, it is not clear whether HFS sequences of monophasic pulses could induce abnormal neuronal responses different from biphasic pulses. Thus, the present study investigates the differences of neuronal responses to HFS of monophasic pulses and biphasic pulses.Methods: Orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of the two types of pulses (with a 1-min duration) were delivered by bipolar electrodes to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in-vivo, respectively. Responses of CA1 pyramidal neurons to the stimulations were recorded in the CA1 region. Single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFS to evoke population spikes for evaluating the baseline and the recovery of neuronal activity. Results: Spreading depression (SD) appeared during sequences of 200 Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200 Hz biphasic O-HFS (0/6). The potential waveform of SD was accompanied by a preceding burst of population spikes, propagated slowly, silenced neuronal firing temporarily and resulted in a non-recovery of orthodromically-evoked population spikes (OPS) after the O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic and biphasic pulses (0/5 and 0/6, respectively) nor during the A-HFS of 200 Hz pulses (0/9). However, the antidromically-evoked population spikes (APS) only recovered partially after the 200 Hz A-HFS of monophasic pulses.Conclusions: The O-HFS with a high enough frequency of monophasic pulses may induce the abnormal neuron activity of SD instantaneously, which may be used as a biomarker to warn the damages caused by improper stimulations in brain tissues.