Measurement of Basal Neurotransmitter Levels Using Convolution-Based Nonfaradaic Current Removal

Abstract

Fast-scan cyclic voltammetry permits robust subsecond measurements of in vivo neurotransmitter dynamics, resulting in its established use in elucidating these species' roles in the actions of behaving animals. However, the technique's limitations, namely the need for digital background subtraction for analytical signal resolution, have restricted the information obtainable largely to that about phasic neurotransmitter release on the second-to-minute time scale. The study of basal levels of neurotransmitters and their dynamics requires a means of isolating the portion of the background current arising from neurotransmitter redox reactions. Previously, we reported on the use of a convolution-based method for prediction of the resistive-capacitive portion of the carbon-fiber microelectrode background signal, to improve the information content of background-subtracted data. Here we evaluated this approach for direct analytical signal isolation. First, protocol modifications (i.e., applied waveform and carbon-fiber type) were optimized to permit simplification of the interfering background current to components that are convolution-predictable. It was found that the use of holding potentials of at least 0.0 V, as well as the use of pitch-based carbon fibers, improved the agreement between convolution predictions and the observed background. Subsequently, it was shown that measurements of basal dopamine concentrations are possible with careful control of the electrode state. Successful use of this approach for measurement of in vivo basal dopamine levels is demonstrated, suggesting the approach may serve as a useful tool in expanding the capabilities of fast-scan cyclic voltammetry.

Fast serotonin voltammetry as a versatile tool for mapping dynamic tissue architecture: I. Responses at carbon fibers describe local tissue physiology

“…As such, subtle alterations in the function of these modulators are thought to underlie the phenotypes of many disorders of the brain (Owens and Nemeroff ; Abi‐Dargham et al ; Volkow and Fowler ; Oades ; Muller et al ). To better understand the functional importance of messengers like serotonin in the brain, analytical measurements of neurotransmitters is a thriving and rapidly evolving field (Meunier et al ; Johnson et al ; Shen et al ). To this end, we have thus far focused on pioneering in vivo measurements of evoked and ambient serotonin using fast‐scan cyclic voltammetry (FSCV) and fast‐scan controlled adsorption voltammetry (FSCAV) at carbon fiber microelectrodes (CFMs) (Hashemi et al ; Abdalla et al ).…”

Automatic and Reliable Quantification of Tonic Dopamine Concentrations In Vivo Using a Novel Probabilistic Inference Method

“…The in vivo recordings utilizing the peak-based method estimated the tonic level of DA in the striatum of anesthetized rat to be approximately 1000 nM for this animal, which is 9- to 25-fold higher than previous reports. 15 , 16 , 18 , 19 …”

3D Fuzzy Graphene Microelectrode Array for Neurotransmitter Sensing at Sub-cellular Spatial Resolution

“…To assess the selectivity of the 3DFG microelectrodes towards the most common neurochemicals found throughout the complex brain environment, we characterized the DA sensing capabilities of the electrodes in presence of 200 μM ascorbic acid (AA), 10 μM uric acid (UA), 10 μM dihydroxyphenylacetic acid (DOPAC). The concentration of DA was kept constant at 100 nM since similar DA concentrations were measured in the rat's dorsal striatum using square wave voltammetry (82 ± 6 nM) (Taylor et al 2019) and multiple cyclic square wave voltammetry (120 ± 18 nM) (Oh et al 2018); and in the nucleus accumbens of both mice and rats, using fast scan controlled adsorption voltammetry (90 ± 9 nM) (Atcherley et al 2015) and convolution-based FSCV(41 ± 13 nM) (Johnson et al 2018), respectively. Our results show that 3DFG microelectrodes of 50 x 50 µm 2 ( Supplementary Figure 4.A-B), 2 x 2 µm 2 (Supplementary Figure 4.…”