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Monitoring serotonin signaling on a subsecond time scale.

Dankoski EC, Wightman RM - Front Integr Neurosci (2013)

Bottom Line: Microdialysis studies have provided a clear picture of how ambient serotonin levels fluctuate with regard to behavioral states and pharmacological manipulation, and anatomical and electrophysiological studies describe the location and activity of serotonin and its targets.Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can detect minute changes in neurotransmitter concentration on the same temporal and spatial dimensions as extrasynaptic neurotransmission.Subsecond measurements both in vivo and in brain slice preparations enable us to tease apart the processes of release and uptake.

View Article: PubMed Central - PubMed

Affiliation: Curriculum in Neurobiology, University of North Carolina Chapel Hill, NC, USA.

ABSTRACT
Serotonin modulates a variety of processes throughout the brain, but it is perhaps best known for its involvement in the etiology and treatment of depressive disorders. Microdialysis studies have provided a clear picture of how ambient serotonin levels fluctuate with regard to behavioral states and pharmacological manipulation, and anatomical and electrophysiological studies describe the location and activity of serotonin and its targets. However, few techniques combine the temporal resolution, spatial precision, and chemical selectivity to directly evaluate serotonin release and uptake. Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can detect minute changes in neurotransmitter concentration on the same temporal and spatial dimensions as extrasynaptic neurotransmission. Subsecond measurements both in vivo and in brain slice preparations enable us to tease apart the processes of release and uptake. These studies have particularly highlighted the significance of regulatory mechanisms to proper functioning of the serotonin system. This article will review the findings of FSCV investigations of serotonergic neurotransmission and discuss this technique's potential in future studies of the serotonin system.

No MeSH data available.


Related in: MedlinePlus

In vitro calibration of microelectrodes. (A) Voltage potential waveform, described by Jackson et al. (1995), for detection of serotonin. (B) Cyclic voltammograms (current-voltage curves) obtained for known concentrations of serotonin injected into a flow cell apparatus. The concentration (right) and its corresponding oxidation current amplitude (left axis) are noted by dashed lines. (C) Maximal oxidation current vs. concentration of serotonin. The data are fit to a linear regression (black line), the slope of which gives a calibration factor for serotonin measured at these electrodes.
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Figure 1: In vitro calibration of microelectrodes. (A) Voltage potential waveform, described by Jackson et al. (1995), for detection of serotonin. (B) Cyclic voltammograms (current-voltage curves) obtained for known concentrations of serotonin injected into a flow cell apparatus. The concentration (right) and its corresponding oxidation current amplitude (left axis) are noted by dashed lines. (C) Maximal oxidation current vs. concentration of serotonin. The data are fit to a linear regression (black line), the slope of which gives a calibration factor for serotonin measured at these electrodes.

Mentions: FSCV is an electrochemical technique that detects changes in endogenous neurotransmitter levels rapidly enough to distinguish release and uptake events in brain tissue. The monoamine neurotransmitters dopamine, norepinephrine, and serotonin are well-suited to voltammetric detection because they oxidize predictably and at low potentials. To evaluate changes in neurotransmitter concentration, FSCV measures the current generated by the oxidation of a neurotransmitter. Oxidation is driven by a potential waveform applied to a carbon-fiber sensor. The current generated is proportional to the concentration of analyte at the carbon surface, so the current-to-concentration relationship can be quantified by calibrating microelectrodes in authentic standards before or after experimental use. Chemical selectivity, or the ability to identify the neurotransmitter being measured, is facilitated by analyzing the plot of generated current vs. applied potential. This current-voltage curve is termed the cyclic voltammogram. Monoamines oxidize and reduce at predictable potentials, and their cyclic voltammograms have a characteristic shape that is easy to recognize. An example of a voltage waveform, cyclic voltammograms, and in vitro calibration is shown in Figure 1. The “fast-scan” in the technique's name refers to the potential waveform, which is applied rapidly and repeatedly, producing up to 10 cyclic voltammograms per second. The carbon-fiber microelectrode sensors used in FSCV have small dimensions (5 × 100 μm), and this small size enables sampling from as few as 100 synapses at a time, with the electrode targeted to a discrete brain region. Thus, FSCV is a technique for which temporal and spatial scales of data collection are compatible with monitoring neurotransmission.


Monitoring serotonin signaling on a subsecond time scale.

Dankoski EC, Wightman RM - Front Integr Neurosci (2013)

In vitro calibration of microelectrodes. (A) Voltage potential waveform, described by Jackson et al. (1995), for detection of serotonin. (B) Cyclic voltammograms (current-voltage curves) obtained for known concentrations of serotonin injected into a flow cell apparatus. The concentration (right) and its corresponding oxidation current amplitude (left axis) are noted by dashed lines. (C) Maximal oxidation current vs. concentration of serotonin. The data are fit to a linear regression (black line), the slope of which gives a calibration factor for serotonin measured at these electrodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672682&req=5

Figure 1: In vitro calibration of microelectrodes. (A) Voltage potential waveform, described by Jackson et al. (1995), for detection of serotonin. (B) Cyclic voltammograms (current-voltage curves) obtained for known concentrations of serotonin injected into a flow cell apparatus. The concentration (right) and its corresponding oxidation current amplitude (left axis) are noted by dashed lines. (C) Maximal oxidation current vs. concentration of serotonin. The data are fit to a linear regression (black line), the slope of which gives a calibration factor for serotonin measured at these electrodes.
Mentions: FSCV is an electrochemical technique that detects changes in endogenous neurotransmitter levels rapidly enough to distinguish release and uptake events in brain tissue. The monoamine neurotransmitters dopamine, norepinephrine, and serotonin are well-suited to voltammetric detection because they oxidize predictably and at low potentials. To evaluate changes in neurotransmitter concentration, FSCV measures the current generated by the oxidation of a neurotransmitter. Oxidation is driven by a potential waveform applied to a carbon-fiber sensor. The current generated is proportional to the concentration of analyte at the carbon surface, so the current-to-concentration relationship can be quantified by calibrating microelectrodes in authentic standards before or after experimental use. Chemical selectivity, or the ability to identify the neurotransmitter being measured, is facilitated by analyzing the plot of generated current vs. applied potential. This current-voltage curve is termed the cyclic voltammogram. Monoamines oxidize and reduce at predictable potentials, and their cyclic voltammograms have a characteristic shape that is easy to recognize. An example of a voltage waveform, cyclic voltammograms, and in vitro calibration is shown in Figure 1. The “fast-scan” in the technique's name refers to the potential waveform, which is applied rapidly and repeatedly, producing up to 10 cyclic voltammograms per second. The carbon-fiber microelectrode sensors used in FSCV have small dimensions (5 × 100 μm), and this small size enables sampling from as few as 100 synapses at a time, with the electrode targeted to a discrete brain region. Thus, FSCV is a technique for which temporal and spatial scales of data collection are compatible with monitoring neurotransmission.

Bottom Line: Microdialysis studies have provided a clear picture of how ambient serotonin levels fluctuate with regard to behavioral states and pharmacological manipulation, and anatomical and electrophysiological studies describe the location and activity of serotonin and its targets.Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can detect minute changes in neurotransmitter concentration on the same temporal and spatial dimensions as extrasynaptic neurotransmission.Subsecond measurements both in vivo and in brain slice preparations enable us to tease apart the processes of release and uptake.

View Article: PubMed Central - PubMed

Affiliation: Curriculum in Neurobiology, University of North Carolina Chapel Hill, NC, USA.

ABSTRACT
Serotonin modulates a variety of processes throughout the brain, but it is perhaps best known for its involvement in the etiology and treatment of depressive disorders. Microdialysis studies have provided a clear picture of how ambient serotonin levels fluctuate with regard to behavioral states and pharmacological manipulation, and anatomical and electrophysiological studies describe the location and activity of serotonin and its targets. However, few techniques combine the temporal resolution, spatial precision, and chemical selectivity to directly evaluate serotonin release and uptake. Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can detect minute changes in neurotransmitter concentration on the same temporal and spatial dimensions as extrasynaptic neurotransmission. Subsecond measurements both in vivo and in brain slice preparations enable us to tease apart the processes of release and uptake. These studies have particularly highlighted the significance of regulatory mechanisms to proper functioning of the serotonin system. This article will review the findings of FSCV investigations of serotonergic neurotransmission and discuss this technique's potential in future studies of the serotonin system.

No MeSH data available.


Related in: MedlinePlus