Developing Nanoscale Analytical Platform for Interrogating Neurotransmission Dynamics in Real-time

A major challenge in the field of neuroanalysis is to elucidate synaptic neurochemistry as well as to probe the dynamics of the diverse range of neurotransmitters. Our recent work has expanded the capability of electrochemistry in neuroanalysis to encompass both redox-active and non-redox active transmitters at the nanoscale. The selective detection for non-redox-active neurotransmitters, i.e., acetylcholine, is based on ion transfer across a nanoscale liquid/liquid junction, that is formed between two immiscible electrolyte solutions (1). Recently, we unveiled the transmission dynamics of cholinergic transmitters at synaptic cleft (a nanojunction where brain communication occurs), generating information inaccessible by current existing methodologies (2), where a multi-vesicular-exocytosis hypothesis was proposed. We also demonstrated a nanometer resolution study of single cell signaling in real-time where nanoelectrodes are positioned at around 100 nanometers away from the release sites to achieve a high signal to noise ratio (3). The nanometer resolution imaging was accomplished with Scanning Electrochemical Microscopy. We also developed dual functionality nanoelectrodes to study the co-release of multiple groups of transmitters, with one channel be the carbon nanodisk electrode for monoamine transmitter detection and a second channel be liquid/liquid junction electrode for cholinergic transmitter detection. Additionally, we are developing the miniaturized liquid/liquid junction electrodes to measure acetylcholine real-time dynamics in live mice brain. Overall, the methodologies we have developed are broadly applicable to tackle a broad range of neurological disorders and diseases.