Automatic and Reliable Quantification of Tonic Dopamine Concentrations In Vivo Using a Novel Probabilistic Inference Method

Abstract

Dysregulation of the neurotransmitter dopamine (DA) is implicated in several neuropsychiatric conditions. Multiple-cyclic square-wave voltammetry (MCSWV) is a state-of-the-art technique for measuring tonic DA levels with high sensitivity (<5 nM), selectivity, and spatiotemporal resolution. Currently, however, analysis of MCSWV data requires manual, qualitative adjustments of analysis parameters, which can inadvertently introduce bias. Here, we demonstrate the development of a computational technique using a statistical model for standardized, unbiased analysis of experimental MCSWV data for unbiased quantification of tonic DA. The oxidation current in the MCSWV signal was predicted to follow a lognormal distribution. The DA-related oxidation signal was inferred to be present in the top 5% of this analytical distribution and was used to predict a tonic DA level. The performance of this technique was compared against the previously used peak-based method on paired in vivo and post-calibration in vitro datasets. Analytical inference of DA signals derived from the predicted statistical model enabled high-fidelity conversion of the in vivo current signal to a concentration value via in vitro post-calibration. As a result, this technique demonstrated reliable and improved estimation of tonic DA levels in vivo compared to the conventional manual post-processing technique using the peak current signals. These results show that probabilistic inference-based voltammetry signal processing techniques can standardize the determination of tonic DA concentrations, enabling progress toward the development of MCSWV as a robust research and clinical tool.

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

“…The microdialysis is widely used for measuring neurochemical concentrations with high selectivity and specificity [12,13]. However, this technique has drawbacks when compared to electrochemical methods such as fast scan cyclic voltammetry (FSCV) in terms of its large microdialysis probe size (> 200 μm) and limited temporal resolution (< 1 min) [14][15][16].…”

Cocaine-Induced Changes in Tonic Dopamine Concentrations Measured Using Multiple-Cyclic Square Wave Voltammetry in vivo

“…Microdialysis has been utilized for sampling neurochemical substances, such as dopamine with high selectivity and sensitivity. However, it has several drawbacks when compared to electrochemical techniques ( Robinson et al, 2003 ; Heien et al, 2004 ; Chefer et al, 2009 ; Rodeberg et al, 2017 ; Kim et al, 2021 ). These include limited temporal resolution ( ≥ 1 min) in comparison to voltammetry (milliseconds to seconds), and the relatively large dimensions of dialysis probes (typically > 200 μm), resulting in variable physicochemical characteristics, tissue damage, and relatively low spatiotemporal resolution ( Morelli et al, 1992 ; Di Chiara et al, 1993 ; Blaha et al, 1996 ; Chefer et al, 2009 ; Oh et al, 2018 ; Rusheen et al, 2020 ).…”

“…The time resolution is 10 s, which is slower than FSCV but is well-matched to the timescale of changes in tonic concentrations of dopamine relevant to the pathologies of interest ( Schultz, 2007 ). Since M-CSWV utilizes square waveforms, M-CSWV is able to harvest higher dimensional data for analysis that leads to higher sensitivity and selectivity than other tonic level measurement techniques ( Kim et al, 2019 ; Kim et al, 2021 ).…”