This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

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Keywords Computational neuroscience, Patch-clamp recordings, Pulsatile stimulation, Purkinje cells, Switched-mode operation
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Journal Frontiers in Neuroengineering
van Dongen, M, Hoebeek, F.E, Koekkoek, S.K.E, de Zeeuw, C.I, & Serdijn, W. (2015). High frequency switched-mode stimulation can evoke post synaptic responses in cerebellar principal neurons. Frontiers in Neuroengineering, 8(MAR). doi:10.3389/fneng.2015.00002