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In Vivo Ambient Serotonin Measurements at Carbon-Fiber Microelectrodes

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Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, United States
Department of Research, Mayo Clinic, Scottsdale, Arizona 85453, United States
§ Department of Statistics, University of South Carolina, 1523 Greene Street, Columbia, South Carolina 29208, United States
Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Blvd., Tucson, Arizona 85721, United States
Cite this: Anal. Chem. 2017, 89, 18, 9703–9711
Publication Date (Web):August 10, 2017
Copyright © 2017 American Chemical Society

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    The mechanisms that control extracellular serotonin levels in vivo are not well-defined. This shortcoming makes it very challenging to diagnose and treat the many psychiatric disorders in which serotonin is implicated. Fast-scan cyclic voltammetry (FSCV) can measure rapid serotonin release and reuptake events but cannot report critically important ambient serotonin levels. In this Article, we use fast-scan controlled adsorption voltammetry (FSCAV), to measure serotonin’s steady-state, extracellular chemistry. We characterize the “Jackson” voltammetric waveform for FSCAV and show highly stable, selective, and sensitive ambient serotonin measurements in vitro. In vivo, we report basal serotonin levels in the CA2 region of the hippocampus as 64.9 ± 2.3 nM (n = 15 mice, weighted average ± standard error). We electrochemically and pharmacologically verify the selectivity of the serotonin signal. Finally, we develop a statistical model that incorporates the uncertainty in in vivo measurements, in addition to electrode variability, to more critically analyze the time course of pharmacological data. Our novel method is a uniquely powerful analysis tool that can provide deeper insights into the mechanisms that control serotonin’s extracellular levels.

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