Choline- and Acetylcholine-Sensitive Microelectrodes

The purpose of this chapter is to provide an overview of the use of enzyme-based microelectrodes and amperometric methods to detect and quantify extracellular levels of choline and acetylcholine (ACh). Our focus will be on the application and evolution of these biosensor techniques for use in vivo rather than the electrochemical principles underlying their development and operation. For the latter topic, one is directed to previous reviews [1] or other chapters in this volume [2]. We begin with a brief introduction contrasting enzyme-based microelectrodes with microdialysis techniques for studying chemoanatomy and the neurochemical correlates of behavior. Next, we introduce the reader to the principles of detection utilized by enzyme-based microelectrodes and discuss strategies that are being employed for enhancing the selectivity of these recording devices. We then turn our attention to the choline-sensitive microelectrode and contrast two styles of microelectrodes, a carbon fiber/filament microelectrode and the multi-site microelectrode array currently used in our laboratories. We then summarize applications of the choline-sensitive microelectrodes in vivo and present, in some detail, empirical data from our laboratory using the choline-sensitive microelectrode array to measure rapid changes in extracellular choline as a potential marker for cortical cholinergic transmission. We then present recent data from our own laboratory on the development of an ACh-sensitive microelectrode array that should provide an even more direct measure of ACh release. Finally, we conclude with a discussion of the challenges confronting the use of enzyme-based microelectrodes as well as several future applications of the microelectrode arrays.