A baseline drift detrending technique for fast scan cyclic voltammetry.

Fast scan cyclic voltammetry (FSCV) has been commonly used to measure extracellular neurotransmitter concentrations in the brain. Due to the unstable nature of the background currents inherent in FSCV measurements, analysis of FSCV data is limited to very short amounts of time using traditional background subtraction. In this paper, we propose the use of a zero-phase high pass filter (HPF) as the means to remove the background drift. Instead of the traditional method of low pass filtering across voltammograms to increase the signal to noise ratio, a HPF with a low cutoff frequency was applied to the temporal dataset at each voltage point to remove the background drift. As a result, the HPF utilizing cutoff frequencies between 0.001 Hz and 0.01 Hz could be effectively used to a set of FSCV data for removing the drifting patterns while preserving the temporal kinetics of the phasic dopamine response recorded in vivo. In addition, compared to a drift removal method using principal component analysis, this was found to be significantly more effective in reducing the drift (unpaired t-test p < 0.0001, t = 10.88) when applied to data collected from Tris buffer over 24 hours although a drift removal method using principal component analysis also showed the effective background drift reduction. The HPF was also applied to 5 hours of FSCV in vivo data. Electrically evoked dopamine peaks, observed in the nucleus accumbens, were clearly visible even without background subtraction. This technique provides a new, simple, and yet robust, approach to analyse FSCV data with an unstable background.

Monitoring In Vivo Changes in Tonic Extracellular Dopamine Level by Charge-Balancing Multiple Waveform Fast-Scan Cyclic Voltammetry.

Dopamine (DA) modulates central neuronal activity through both phasic (second to second) and tonic (minutes to hours) terminal release. Conventional fast-scan cyclic voltammetry (FSCV), in combination with carbon fiber microelectrodes, has been used to measure phasic DA release in vivo by adopting a background subtraction procedure to remove background capacitive currents. However, measuring tonic changes in DA concentrations using conventional FSCV has been difficult because background capacitive currents are inherently unstable over long recording periods. To measure tonic changes in DA concentrations over several hours, we applied a novel charge-balancing multiple waveform FSCV (CBM-FSCV), combined with a dual background subtraction technique, to minimize temporal variations in background capacitive currents. Using this method, in vitro, charge variations from a reference time point were nearly zero for 48 h, whereas with conventional background subtraction, charge variations progressively increased. CBM-FSCV also demonstrated a high selectivity against 3,4-dihydroxyphenylacetic acid and ascorbic acid, two major chemical interferents in the brain, yielding a sensitivity of 85.40 ± 14.30 nA/µM and limit of detection of 5.8 ± 0.9 nM for DA while maintaining selectivity. Recorded in vivo by CBM-FSCV, pharmacological inhibition of DA reuptake (nomifensine) resulted in a 235 ± 60 nM increase in tonic extracellular DA concentrations, while inhibition of DA synthesis (α-methyl-dl-tyrosine) resulted in a 72.5 ± 4.8 nM decrease in DA concentrations over a 2 h period. This study showed that CBM-FSCV may serve as a unique voltammetric technique to monitor relatively slow changes in tonic extracellular DA concentrations in vivo over a prolonged time period.