Development of a microelectrode array system for simultaneous measurement of field potential and glutamate release in brain slices.

Disorders of the central nervous system and complex side effects caused by abnormal neurotransmitter release have been widely reported. Simultaneous real-time measurement of neurotransmitter release and field potential (FP) could provide insights into the relationship between chemical signaling and neural electrical activity. In this study, we developed a microelectrode array (MEA) system capable of simultaneously recording FP and electrochemical (EC) signals. To enable neurotransmitter detection, we fabricated an enzyme-modified carbon nanotube (CNT)-MEA using glutamate oxidase (Glu-Ox) and horseradish peroxidase (HRP) immobilized in an osmium-based redox polymer. Glu-Ox catalyzes the oxidative deamination of glutamate to produce hydrogen peroxide (H2O2), which is then electrochemically reduced by HRP-Os, generating a current proportional to glutamate concentration. This dual-enzyme cascade provides high substrate specificity and efficient electron transfer under low overpotentials, enabling sensitive detection of glutamate at nanomolar levels. Using this system, we simultaneously recorded extracellular potentials and glutamate release from hippocampal brain slices. Following caffeine administration, we observed both enhanced oscillatory FP activity and time-correlated increases in glutamate release. Furthermore, we also achieved the recording of dopamine release from brain slices using this system. These results confirm that the enzyme-modified CNT-MEA and integrated FP/EC recording platform enable real-time, simultaneous monitoring of neuronal activity and neurotransmitter dynamics. This technology provides a powerful tool for investigating neural circuit function, pathological mechanisms, and drug responses.