The brain's complex network relies on electrical and chemical signaling to support its normal functions. Understanding brain circuits requires simultaneously monitoring neurotransmitters and electrophysiological signals. The striatal dopamine circuits are integral to neurological processes such as reward and circadian rhythm regulation, making it highly desirable to monitor both neural activity and dopamine (DA) levels in freely behaving animals. One promising approach involves the implantation of multimodal microelectrode arrays (MEAs). However, chronic electrochemical sensing of DA in freely moving animals faces significant challenges, including biofouling of sensing electrodes and the instability of the Ag/AgCl reference. In this study, we developed two complementary strategies to coat the implanted Ag/AgCl reference and MEA with zwitterionic poly(sulfobetaine methacrylate) (PSB). The PSB coating effectively inhibits protein fouling and inflammatory responses to the MEA, while the PSB hydrogel protects the Ag/AgCl electrodes from delamination in vivo. We achieved stable DA detection and electrophysiological recordings in freely moving mice over four weeks. Weekly electrochemical impedance spectroscopy confirmed the long-term stability of the implanted electrodes. Our method enables multidimensional analysis of behavioral patterns, electrophysiological activity, and DA dynamics. This work advances neurochemical and electrophysiological methodologies by offering reliable tools for longitudinal investigations of brain function in freely behaving animals.
