Cathodic- and anodic-pulses can alternately activate different sub-populations of neurons during sustained high-frequency stimulation of axons in rat hippocampus.

Objective. Charge-balanced biphasic-pulses are commonly used in neural stimulations to prevent possible damages caused by charge accumulations. The lagging anodic-phases of biphasic-pulses may decrease the activation efficiency of stimulations by counteracting the depolarization effect of the leading cathodic-phases. However, a monophasic anodic-pulse alone can itself activate neurons by depolarizing neuronal membrane through a mechanism of virtual cathode. This study aimed to verify the hypothesis that the anodic-phases/pulses in charge-balanced stimulations could play an activation role during sustained high-frequency stimulations (HFSs). Approach. Two types of antidromic HFS (A-HFS) were applied on the alveus of hippocampal CA1 region of anesthetized rats: monophasic-pulse A-HFS of alternate opposite pulses and biphasic-pulse A-HFS with the same frequency of 100 or 200 Hz. The antidromically-evoked population spike was used as a biomarker to evaluate the activation effects of A-HFS pulses. Main results. Despite a significant difference in the initial abilities of anodic- and cathodic-pulses to activate neurons, an anodic-pulse was able to induce similar amount of neuronal firing as a cathodic-pulse during sustained monophasic-pulse A-HFS. Additionally, the amount of neuronal firing induced by the monophasic-pulse A-HFS was similar to that induced by the biphasic-pulse A-HFS consuming a double amount of electrical energy. Furthermore, the alternate cathodic- and anodic-pulses respectively activated different sub-populations of neurons during steady A-HFS. Significance. The anodic-phases/pulses in charge-balanced HFS at axons can play an activation role in addition to a role of charge balance. The study provides important information for designing charge-balanced stimulations and reveals new mechanisms of neural stimulations.