Wireless implantable micro-stimulation device for high frequency bilateral deep brain stimulation in freely moving mice

► This paper describes a new light-weight wireless implantable micro stimulator device for mice. ► The device delivers biphasic pulse patterns to two individual electrode pairs, mimicking the clinical situation. ► Bench-top validation shows that this device reliably delivers continuous bilateral stimulation. ► In vivo implementation indicates that the wireless implantable stimulator in mice does not restrict the animal's mobility and hygiene (grooming behavior). ► As previously shown by others, our in vivo results showed a marked increase in c-fos expression around the electrode tip in the nucleus accumbens in mice following DBS at 100μA. Although deep brain stimulation (DBS) has been proven to be an effective treatment for several neuropsychiatric disorders, such as Parkinson's disease, the underlying working mechanisms are still largely unknown. Behavioral animal models are essential in examining the working mechanisms of DBS and especially mouse models are necessary to investigate the genetic component underlying specific behaviors related to psychiatric diseases. Unfortunately, currently available stimulation devices are unsuitable to test behavior in freely-moving mice. As such, no DBS studies in behaving mice have been reported thus far. In order to overcome this limitation we have developed a new light-weight wireless implantable micro stimulator device for mice that delivers biphasic pulse patterns to two individual electrode pairs, mimicking partly the clinical situation. This paper describes in detail the bench-top validation and in vivo implementation of this device. The results in this study indicate that the wireless implantable stimulator in mice reliably delivers continuous bilateral stimulation, importantly, does not restrict the animals mobility and hygiene (grooming behavior). In vivo testing furthermore showed that stimulation of the mice ventral striatum yields similar results as previously shown by others in rats where conventional deep brain stimulation techniques were used. This newly designed device can now be used in the highly needed DBS behavioral studies in mice, to further investigate the underlying mechanisms of DBS in behavioral animal models for psychiatric disorders.