Use Of Fast-scan Cyclic Voltammetry Research Articles

Defining a Path Toward the Use of Fast-Scan Cyclic Voltammetry in Human Studies.

Fast Scan Cyclic Voltammetry (FSCV) has been used for decades as a neurochemical tool for in vivo detection of phasic changes in electroactive neurotransmitters in animal models. Recently, multiple research groups have initiated human neurochemical studies using FSCV or demonstrated interest in bringing FSCV into clinical use. However, there remain technical challenges that limit clinical implementation of FSCV by creating barriers to appropriate scientific rigor and patient safety. In order to progress with clinical FSCV, these limitations must be first addressed through (1) appropriate pre-clinical studies to ensure accurate measurement of neurotransmitters and (2) the application of a risk management framework to assess patient safety. The intent of this work is to bring awareness of the current issues associated with FSCV to the scientific, engineering, and clinical communities and encourage them to seek solutions or alternatives that ensure data accuracy, rigor and reproducibility, and patient safety.

Miniature FSCV Devices: A Review

Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing method used for measuring the concentration of neurotransmitters within the brain. FSCV is typically conducted using benchtop equipment, providing accurate and high temporal resolution measurements. However, the large size and high cost of benchtop FSCV systems pose significant limitations in widespread preclinical use of FSCV. Recent technological improvements have facilitated the miniaturization of FSCV equipment, creating systems that can be mounted on the subject as they are small and lightweight. One key remaining bottleneck in the emerging miniaturized FSCV systems is that their data typically needs to be transmitted to an external computer for analysis. This paper presents a review on the current miniature FSCV devices. It discusses the latest improvements in voltage scan waveforms that help increase the sensitivity of measuring specific analytes, for use in miniaturized FSCV. It also tabulates analytes that have been detected using FSCV. It also details current issues with FSCV and the latest achievements in post-processing of FSCV data to better identify target analytes. Furthermore, the emerging miniature FSCV devices that have integrated on-board data processing capabilities to mitigate external data processing are discussed. These advances can accelerate neurochemistry research, reducing time spent analysing data on external computers, and allowing for investigation into questions on neurotransmitter dynamics in target brain regions.

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect.

Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.

Hitchhiker's Guide to Voltammetry: Acute and Chronic Electrodes for in Vivo Fast-Scan Cyclic Voltammetry.

Fast-scan cyclic voltammetry (FSCV) has been used for over 20 years to study rapid neurotransmission in awake and behaving animals. These experiments were first carried out with carbon-fiber microelectrodes (CFMs) encased in borosilicate glass, which can be inserted into the brain through micromanipulators and guide cannulas. More recently, chronically implantable CFMs constructed with small diameter fused-silica have been introduced. These electrodes can be affixed in the brain with minimal tissue response, which permits longitudinal measurements of neurotransmission in single recording locations during behavior. Both electrode designs have been used to make novel discoveries in the fields of neurobiology, behavioral neuroscience, and psychopharmacology. The purpose of this Review is to address important considerations for the use of FSCV to study neurotransmitters in awake and behaving animals, with a focus on measurements of striatal dopamine. Common issues concerning experimental design, data collection, and calibration are addressed. When necessary, differences between the two methodologies (acute vs chronic recordings) are discussed. The topics raised in this Review are particularly important as the field moves beyond dopamine toward new neurochemicals and brain regions.

Fast-Scan Cyclic Voltammetry Allows Determination of Electron-Transfer Kinetic Constants in Single Nanoparticle Collision

Here we report the use of Fast-Scan Cyclic Voltammetry (FSCV) to study transient nanoparticle (NP) collision experiments and determine the apparent heterogeneous electron-transfer (ET) rate constant ko and electrocatalytic activity of single NPs. Continuous potential scanning at fast scan rates, for example, up to 500 V/s, and background subtraction enable voltammetric study of single NPs when they collide on a carbon ultramicroelectrode (UME). The FSCV results indicate a substantial potential shift in the CV response of single NPs due to increased mass transfer and it is necessary to consider this effect when analyzing single NP electrocatalysts. FSCV results also reveal that single particle deactivation is associated with a decrease in peak current and an increase in overpotential. Importantly, the use of FSCV coupled with numerical simulations enabled the determination of ko on single NPs, confirming an increase in catalytic activity with decreasing particle size. Moreover, the Gibbs free energy of activation can be estimated from the ko. This work further confirms that FSCV is a powerful method in studying dynamic electrochemical processes such as single NP collisions.

Carbon Nanotubes Grown on Metal Microelectrodes for the Detection of Dopamine.

Microelectrodes modified with carbon nanotubes (CNTs) are useful for the detection of neurotransmitters because the CNTs enhance sensitivity and have electrocatalytic effects. CNTs can be grown on carbon fiber microelectrodes (CFMEs) but the intrinsic electrochemical activity of carbon fibers makes evaluating the effect of CNT enhancement difficult. Metal wires are highly conductive and many metals have no intrinsic electrochemical activity for dopamine, so we investigated CNTs grown on metal wires as microelectrodes for neurotransmitter detection. In this work, we successfully grew CNTs on niobium substrates for the first time. Instead of planar metal surfaces, metal wires with a diameter of only 25 μm were used as CNT substrates; these have potential in tissue applications due to their minimal tissue damage and high spatial resolution. Scanning electron microscopy shows that aligned CNTs are grown on metal wires after chemical vapor deposition. By use of fast-scan cyclic voltammetry, CNT-coated niobium (CNT-Nb) microelectrodes exhibit higher sensitivity and lower ΔEp value compared to CNTs grown on carbon fibers or other metal wires. The limit of detection for dopamine at CNT-Nb microelectrodes is 11 ± 1 nM, which is approximately 2-fold lower than that of bare CFMEs. Adsorption processes were modeled with a Langmuir isotherm, and detection of other neurochemicals was also characterized, including ascorbic acid, 3,4-dihydroxyphenylacetic acid, serotonin, adenosine, and histamine. CNT-Nb microelectrodes were used to monitor stimulated dopamine release in anesthetized rats with high sensitivity. This study demonstrates that CNT-grown metal microelectrodes, especially CNTs grown on Nb microelectrodes, are useful for monitoring neurotransmitters.

Characterization of Fast-Scan Cyclic Voltammetric Electrodes Using Paraffin as an Effective Sealant with In Vitro and In Vivo Applications.

Fast-scan cyclic voltammetry (FSCV) is a powerful technique for measuring sub-second changes in neurotransmitter levels. A great time-limiting factor in the use of FSCV is the production of high-quality recording electrodes; common recording electrodes consist of cylindrical carbon fiber encased in borosilicate glass. When the borosilicate is heated and pulled, the molten glass ideally forms a tight seal around the carbon fiber cylinder. It is often difficult, however, to guarantee a perfect seal between the glass and carbon. Indeed, much of the time spent creating electrodes is in an effort to find a good seal. Even though epoxy resins can be useful in this regard, they are irreversible (seals are permanent), wasteful (epoxy cannot be reused once hardener is added), hazardous (hardeners are often caustic), and require curing. Herein we characterize paraffin as an electrode sealant for FSCV microelectrodes. Paraffin boasts the advantages of near-immediate curing times, simplicity in use, long shelf-life and stable waterproof seals capable of withstanding extended cycling. Borosilicate electrode tips were left intact or broken and dipped in paraffin embedding wax. Excess wax was removed from the carbon surface with xyelenes or by repeated cycling at an extended waveform (-0.4 to 1.4V, 400 V/s, 60 Hz). Then, the waveform was switched to a standard waveform (-0.4 to 1.3V, 400 V/s, 10 Hz) and cycled until stable. Wax-sealing does not inhibit electrode sensitivity, as electrodes detected linear changes in dopamine before and after wax (then xylenes) exposure. Paraffin seals are intact after 11 days of implantation in the mouse, and still capable of measuring transient changes in in vivo dopamine. From this it is clear that paraffin wax is an effective sealant for FSCV electrodes that provides a convenient substitute to epoxy sealants.

Endocannabinoid-Dependent Modulation of Phasic Dopamine Signaling Encodes External and Internal Reward-Predictive Cues

The mesolimbic dopamine (DA) system plays an integral role in incentive motivation and reward seeking and a growing body of evidence identifies signal transduction at cannabinoid receptors as a critical modulator of this system. Indeed, administration of exogenous cannabinoids results in burst firing of DA neurons of the ventral tegmental area and increases extracellular DA in the nucleus accumbens (NAcc). Implementation of fast-scan cyclic voltammetry (FSCV) confirms the ability of cannabinoids to augment DA within the NAcc on a subsecond timescale. The use of FSCV along with newly developed highly selective pharmacological compounds advances our understanding of how cannabinoids influence DA transmission and highlights a role for endocannabinoid-modulated subsecond DAergic activation in the incentive motivational properties of not only external, but also internal reward-predictive cues. For example, our laboratory has recently demonstrated that in mice responding under a fixed-interval (FI) schedule for food reinforcement, fluctuations in NAcc DA signal the principal cue predictive of reinforcer availability – time. That is, as the interval progresses, NAcc DA levels decline leading to accelerated food seeking and the resulting characteristic FI scallop pattern of responding. Importantly, administration of WIN 55,212-2, a synthetic cannabinoid agonist, or JZL184, an indirect cannabinoid agonist, increases DA levels during the interval and disrupts this pattern of responding. Along with a wealth of other reports, these results illustrate the role of cannabinoid receptor activation in the regulation of DA transmission and the control of temporally guided reward seeking. The current review will explore the striatal beat frequency model of interval timing as it pertains to cannabinoid signaling and propose a neurocircuitry through which this system modulates interoceptive time cues.

Chemically resolved transient collision events of single electrocatalytic nanoparticles.

Here we report the use of fast-scan cyclic voltammetry (FSCV) to study transient collision and immobilization events of single electrocatalytic metal nanoparticles (NPs) on an inert electrode. In this study, a fast, repetitive voltage signal is continuously scanned on an ultramicroelectrode and its faradaic signal is recorded. Electrocatalytically active metal NPs are allowed to collide and immobilize on the electrode resulting in the direct recording of the transient voltammetric response of single NPs. This approach enables one to obtain the transient voltammetric response and electrocatalytic effects of single catalytic NPs as they interact with an inert electrode. The use of FSCV has enabled us to obtain chemical information, which is otherwise difficult to study with previous amperometric methods.