Question

Voltametry in vivo for chemical analysis of neurotransmitters in central nervous system

Answer 1

Since their introduction in the early 1970s, in vivo voltammetric methods have provided researchers with a means of studying the dynamics of neurotransmitter release mechanisms in whole animals and brain slices, and more recently in single cells in culture. Using microelectrodes (5–30 µm OD, outside diameter), generally made of carbon, investigators have studied the signaling dynamics of neurotransmitters and neuromodulators such as dopamine (DA), norepinephrine (NE) and serotonin (5‐HT), and more recently nitric oxide (NO) and glutamate. Unlike the complimentary technique known as microdialysis, in vivo voltammetric methods allow for the very rapid (1–200 Hz) and spatially resolved (5–30 by 30–150 µm as compared to 200–300 µm by 1–4 mm) measurement of the dynamic properties of neurochemicals. However, the routine detection limits of such methods are in the 25–50‐nM range for analytes such as DA, 5‐HT and NO, and these do not rival the picomolar detection limits of methods used to analyze microdialysis samples.

These seemingly straightforward methods have been plagued by methodological problems, primarily dealing with the selective and sensitive measurements of neurotransmitters. Microelectrodes and associated recording techniques must be able to measure and identify selectively the analytes of interest without the use of powerful separation and quantitation methods such as high‐performance liquid chromatography coupled to electrochemical detection (HPLC/EC). Improvements in microelectrode technologies and recording methods have greatly enhanced the utility of such methods for a variety of studies.

The purpose of this chapter is to give readers a general introduction to in vivo voltammetric methods that can be applied to studies of neurotransmitter and neuromodulator signaling dynamics in brain tissues and in cells in culture. We discuss the types of microelectrodes that are now used to record neurochemicals as well as surface modifications that are carried out on these microelectrodes to make them more sensitive and selective for different neurochemicals. The different recording methods and some of their inherent strengths and weaknesses are reviewed as well as the instrumentation currently used to record from microelectrodes for such measures. Finally, we discuss some of the applications of these methods and how they compare with other in vivo recording methods such as microdialysis and fiber optic sensors. This review does not focus on the biological systems that have been studied with these methods and the results of such studies. The major purpose is to give the reader an overview of in vivo voltammetry methods and how they can be used to study neurotransmitter and neuromodulator signaling dynamics in biological systems. Future developments in this field hold great promise for developing a large number of new microelectrodes for detecting a variety of neurochemicals in order to gain an understanding of chemical signaling, which is an integral part of central nervous system (CNS) biology and all biological systems.