Monitoring deep brain stimulation by measuring regional brain oxygen responses in freely moving mice

Background: Translational studies investigating the effects of deep brain stimulation (DBS) on brain function up to now mainly relied on BOLD responses measured with fMRI. However, fMRI studies in rodents face technical and practical limitations (e.g., immobilization, sedation or anesthesia, spatial and temporal resolution of data). Direct measurement of oxygen concentration in the brain using electrochemical sensors is a promising alternative to the use of fMRI. Here, we tested for the first time if such measurements can be combined with DBS. New method: We combined bilateral DBS in the internal capsule (IC-DBS) with simultaneous amperometric measurements of oxygen in the medial prefrontal cortex (prelimbic area) and striatum of freely moving mice. Using a two-day within-animal experimental design, we tested the effects of DBS on baseline oxygen concentrations, and on novelty- and restraint-induced increases in oxygen concentration. Results: Basal oxygen levels were stable across the daily sampling periods. Exposure to novelty and immobilization reproducibly increased oxygen concentrations in both areas. IC-DBS did not significantly alter basal oxygen, but reduced the novelty-induced increase in the striatum. Comparison with existing method(s): Amperometric detection of brain oxygen concentration with high temporal and spatial resolution can be performed in a number of key brain areas to study the effects of DBS in animal models of disease. The method is easily implemented and does not require expensive equipment or complicated data analysis processes. Conclusions: Direct and simultaneous measurement of brain oxygen concentration in multiple brain areas can be used to study the effects of bilateral DBS neuromodulation on brain activity in freely moving mice.