Targeted-Modified MultiTransm Microelectrode Arrays Simultaneously Track Dopamine and Cellular Electrophysiology in Nucleus Accumbens during Sleep-Wake Transitions.

Abstract

Cellular-level electrophysiological and neurotransmitter signals serve as key biomarkers of sleep depth, offering insights into the dynamic sleep transitions and the neural mechanisms underlying sleep regulation. Microelectrode arrays (MEAs) provide an innovative solution for in situ, simultaneous detection of these signals with high spatial and temporal resolution. However, despite substantial progress in electrode material development, current multimodal MEA systems remain fundamentally constrained by partial integration. This study aims to address the performance limitations of multimodal MEAs by developing a MultiTransm MEA (MT MEA), integrating a 3-electrode system with site-specific surface modifications: platinum nanoparticle (PtNP)/poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)-modified sites for electrophysiology, PtNP/PEDOT:PSS/Nafion-modified sites for dopamine sensing, and iridium oxide (IrOx)-based on-probe reference electrodes. The directional surface modification strategy was employed to enable compact integration, minimize inter-channel crosstalk, preserve high spatiotemporal resolution for both electrophysiological and electrochemical detection, and ensure long-term operational stability. By incorporating electroencephalography (EEG) and electromyography (EMG), MT MEAs enable real-time in vivo monitoring of sleep dynamics within the nucleus accumbens. Three distinct spike types were identified, whose coordinated activity shaped the sleep architecture. In addition, EEG and local field potential (LFP) signals exhibited distinct patterns during wakefulness, indicating region-specific neural processing. Notably, dopamine release was lowest during non-rapid eye movement (NREM) sleep and peaked during wakefulness, suggesting a neuromodulatory role in sleep-wake transitions. These results demonstrate that MT MEAs are powerful tools for probing neural and neurochemical activity across sleep states, offering new insights into the physiological regulation of sleep.