Electrochemical Analysis of Neurotransmitters

Abstract

Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.

High-resolution imaging of cellular dopamine efflux using a fluorescent nanosensor array

“…Compared with amperometric methods, nanosensor arrays currently exhibit reduced temporal resolution but amperometric methods cannot distinguish molecules of similar redox potential. Therefore, due to the higher chemical selectivity it is more appropriate to compare nanosensor arrays with cyclic voltammetry methods, which also have a time resolution of ∼100 ms (20). An advantage of amperometric methods is their ability to quantify (count) the number of molecules that encounter the electrode.…”

“…1A). This platform has advantages over protein-based fluorescent sensors and semisynthetic protein-fluorophore conjugates on the cell surface in that it has higher sensitivity, time resolution, and lacks photobleaching (18)(19)(20)(21). Electrochemical techniques, although the most advanced for measurement of redox-active neurotransmitters in vitro and in vivo, provide poor spatial resolution (4, 6) to date.…”

Analytical Techniques in Neuroscience: Recent Advances in Imaging, Separation, and Electrochemical Methods

“…168 Wightman and coworkers popularized FSCV at carbon-fiber microelectrodes to measure electroactive neurotransmitters, such as dopamine, norepinephrine, epinephrine, serotonin, histamine and adenosine. 169 FSCV at microelectrodes facilitates high temporal resolution monitoring of release and uptake of neurochemicals on sub-second timescales. In this section, we focus on recent advancements in FSCV for neurochemical measurements, including technical advances in FSCV waveform modification strategies.…”

Construction of Training Sets for Valid Calibration of in Vivo Cyclic Voltammetric Data by Principal Component Analysis

“…1 One electrochemical technique, fast-scan cyclic voltammetry (FSCV), is particularly useful to detect subsecond dopamine release in behaving animals. The cyclic voltammograms (CVs) provided by this technique give chemically specific information for identification of contributing species.…”