Recent Progress in Quantitatively Monitoring Vesicular Neurotransmitter Release and Storage With Micro/Nanoelectrodes

Exocytosis is one of the essential steps for chemical signal transmission between neurons. In this process, vesicles dock and fuse with the plasma membrane and release the stored neurotransmitters through fusion pores into the extracellular space, and all of these steps are governed with various molecules, such as proteins, ions, and even lipids. Quantitatively monitoring vesicular neurotransmitter release in exocytosis and initial neurotransmitter storage in individual vesicles is significant for the study of chemical signal transmission of the central nervous system (CNS) and neurological diseases. Electrochemistry with micro/nanoelectrodes exhibits great spatial–temporal resolution and high sensitivity. It can be used to examine the exocytotic kinetics from the aspect of neurotransmitters and quantify the neurotransmitter storage in individual vesicles. In this review, we first introduce the recent advances of single-cell amperometry (SCA) and the nanoscale interface between two immiscible electrolyte solutions (nanoITIES), which can monitor the quantity and release the kinetics of electrochemically and non-electrochemically active neurotransmitters, respectively. Then, the development and application of the vesicle impact electrochemical cytometry (VIEC) and intracellular vesicle impact electrochemical cytometry (IVIEC) and their combination with other advanced techniques can further explain the mechanism of neurotransmitter storage in vesicles before exocytosis. It has been proved that these electrochemical techniques have great potential in the field of neuroscience.

Intracellular injection of phospholipids directly alters exocytosis and the fraction of chemical release in chromaffin cells as measured by nano-electrochemistry

Amperometry and intracellular vesicle impact electrochemical cytometry with nanotip electrodes were used to monitor the effects on exocytosis and vesicular storage after nano-injection of phospholipids with different geometries into secretory cells.

Electrochemistry at the Synapse

Electrochemical measurements of neurotransmitters provide insight into the dynamics of neurotransmission. In this review, we describe the development of electrochemical measurements of neurotransmitters and how they started with extrasynaptic measurements but now are pushing toward synaptic measurements. Traditionally, biosensors or fast-scan cyclic voltammetry have monitored extrasynaptic levels of neurotransmitters, such as dopamine, serotonin, adenosine, glutamate, and acetylcholine. Amperometry and electrochemical cytometry techniques have revealed mechanisms of exocytosis, suggesting partial release. Advances in nanoelectrodes now allow spatially resolved, electrochemical measurements in a synapse, which is only 20–100 nm wide. Synaptic measurements of dopamine and acetylcholine have been made. In this article, electrochemical measurements are also compared to optical imaging and mass spectrometry measurements, and while these other techniques provide enhanced spatial or chemical information, electrochemistry is best at monitoring real-time neurotransmission. Future challenges include combining electrochemistry with these other techniques in order to facilitate multisite and multianalyte monitoring.