In vivo validation of a new portable stimulator for chronic deep brain stimulation in freely moving rats

Abstract

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered as a gold standard therapy for the alleviation of motor symptoms in Parkinson’s disease (PD). This success paved the way to its application for other neurological and psychiatric disorders. In this context, we aimed to develop a rodent-specific stimulator with characteristics similar to those used in patients. New methodWe designed a stimulator that can be connected to an electrode container with options for bilateral or unilateral stimulation selection and offers a wide range of frequencies, pulse widths and intensities, constant current, biphasic current-control and charge balancing. Dedicated software was developed to program these parameters and the device was tested on a bilateral 6-hydroxydopamine (6-OHDA) rat model of PD. ResultsThe equipment was well tolerated by the animals with a good general welfare. STN stimulation (130 Hz frequency, 0.06 ms pulse width, 150 μA average intensity) improved the motor deficits induced by 6-OHDA as it significantly increased the number of movements compared to the values obtained in the same animals without STN stimulation. Furthermore, it restored motor coordination by significantly increasing the time spent on the rotarod bar. ConclusionWe successfully developed and validated a new portable and programmable stimulator for freely moving rats that delivers a large range of stimulation parameters using bilateral biphasic current-control and charge balancing to maximize tissue safety. This device can be used to test deep brain stimulation in different animal models of human brain diseases.