Expanding the Scope and Usability of Fast Voltammetric Measurements

ABSTRACT: Background-subtracted fast-scan cyclic voltammetry (FSCV) is unrivaled in its ability to monitor neurochemical dynamics. This approach permits highly localized analysis of multi-neurochemical release and reuptake events at single cells, in tissue slices, and in intact animal subjects over the course of seconds, hours, weeks, or months.

However, it is used almost exclusively for quantification of dopamine (DA) over short (< 2 minute) time windows, and exploited almost entirely by users with formal training in voltammetry. This under-utilization is stunning, because FSCV is attractive in almost any neurochemical monitoring application where cellular-scale spatial

resolution, speed, and accuracy are essential. The transfer of electrons across the electrode/solution interface is the source of the signal and it is fundamentally dictated by the physical properties of that interface at any given moment, which change (a lot!) over the course of an experiment. This can confound data interpretation,

particularly when experimental conditions also change in an uncontrolled fashion. This is the biggest factor that has restricted the broad application of this technique to additional molecules and user groups. To address these issues, we plan to use standard FSCV instrumentation to continuously monitor the physical properties of the

dynamic carbon/solution interface using electrochemical impedance spectroscopy during fast voltammetric experiments, and to directly map this information onto shifts in electrochemical performance, in real time. This will enable reliable prediction of - and thus correction for - shifts in voltammetric performance that develop as

experimental conditions change. The first goal is to enable continuous mapping of impedance information onto electrochemical performance. This will provide a predictive framework for correcting impedance-related shifts in electrode performance when the system impedance is known. The second goal is to develop, evaluate, and

optimize an automated feedback mechanism to account for distortions to the voltammetric data that result from uncompensated shifts in system impedance. This will simplify interpretation of complex FSCV data, improving quality and enabling multi-transmitter monitoring. Performance will be validated by recording the effects of

cocaine on coordinated glutamate and DA signaling in striatum, which has been implicated in cocaine abuse. The project is innovative, because it will shift researchers from traditional methods of calibration that use static characterization factors acquired in irrelevant recording environments, to an entirely new way of thinking about

signal standardization that accounts for ongoing shifts in system impedance during the course of the experiment. It is significant, because it minimizes distortion of complex FSCV data, enabling measurements of coordinated neurochemical signaling and providing for improved quantification, especially in instances where a traditional

approach to calibration is precluded. Ultimately, this work will enable countless new neurochemical investigations.