Micromagnetic Stimulation (μMS) Controls Dopamine Release: Anin vivoStudy Using WINCSHarmoni

Abstract

Objective: Research into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the in vivo changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS Harmoni tool to study the real time in vivo changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy. Approach: Although still in its infancy, micromagnetic stimulation using micro-meter sized coils or microcoils has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These microcoils are powered by a time-varying current which generates a magnetic field. As per Faradays Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped microcoil to stimulate the medial forebrain bundle (MFB) of the rodent brain in vivo. The evoked in vivo dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV). Results: Our experiments report that microcoils can successfully activate the MFB in rodent brains, triggering dopamine release in vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the microcoil. Furthermore, varied intensities of micromagnetic stimulation can control the concentration of dopamine releases in the striatum. Significance: This work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like micromagnetic stimulation, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for micromagnetic stimulation to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.