Dopamine measurement during prolonged deep brain stimulation: A proof-of-principle study of paired pulse voltammetry

Purpose: Deep Brain Stimulation (DBS) has been effective in treating various neurological and psychiatric disorders; however, its underlying mechanism hasn't been completely understood. Fast scan cyclic voltammetry (FSCV) is a valuable tool to elucidate underlying neurotransmitter mechanisms of DBS, due to its sub-second temporal resolution and direct identification of analytes. However, since DBS-like high frequency stimulation evokes neurotransmitter release as well as extracellular pH shift, it is hard to isolate the neurotransmitter signal from the complex environment. Here we demonstrate the efficacy of a modified FSCV technique, Paired Pulse Voltammetry (PPV), in detecting dopamine (DA) release in the caudate nucleus during long-term electrical stimulation of the medial forebrain bundle (MFB) in the rat. Methods: Unlike traditional FSCV applying a single triangular waveform, PPV employs a binary waveform with a specific time gap (2.2 ms) in between the comprising pulses. DA measurement was performed with a carbon fiber microelectrode placed in the caudate nucleus and a twisted bipolar stimulating electrode in the MFB. PPV data was collected with the Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Results: Using PPV, the detection of DA was evident throughout the long-term stimulation (5 minutes); however, without PPV, in vivo environmental changes including pH shift eventually obscured the characteristic oxidation current of DA at 0.6V. Conclusions: These results indicate that PPV can be a valuable tool to accurately determine DA dynamics in a complex in vivo environment during long-term electrical stimulation.