A Custom Made Electrode Construct and Reliable Implantation Method That Allows for Long-Term Bilateral Deep Brain Stimulation in Mice

Abstract

Objectives: The underlying mechanisms behind the therapeutic and side effects of deep brain stimulation (DBS) need further investigation. The utilization of transgenic mouse lines is a suitable approach to better understand the cellular and network effects of DBS. However, not many bilateral DBS studies have been conducted in mice. This might be due to a lack of commercially available bilateral DBS constructs. Materials and Methods: We developed an approach to perform repetitive long-term DBS in freely moving mice. In this study, we implanted an in-house custom-made DBS construct containing two bipolar concentric electrodes to target the subthalamic nucleus (STN) bilaterally. Subsequently, we stimulated half of the animals with clinically relevant parameters three to five times a week with a duration of 20 min for ten weeks. Several behavioral tests were conducted of which the open field test (OFT) is shown to validate the reliability of this electrode construct and implantation method. Furthermore, we performed fiber photometry measurements to show the acute effect of STN-DBS on serotonin network activity in the dorsal raphe nucleus. Results: Repetitive DBS and long-term behavioral testing were performed without complications. STN-DBS resulted in an increase of the distance traveled in the OFT and a reduction of calcium levels in serotonergic neurons of the dorsal raphe nucleus. None of the mice had lost their electrodes and postmortem evaluation of the tissue showed accurate targeting of the STN without excessive gliosis. Conclusion: The DBS electrode construct and implantation method described can be used for long-term DBS studies to further investigate the mechanisms underlying DBS.