Frontiers in Neurotransmitter Probes: Innovations and Perspectives in Norepinephrine Detection Technology

Norepinephrine (NE), the primary neurotransmitter of locus coeruleus projections, plays a crucial role in regulating arousal, emotion, memory, and stress responses. Its dysregulation is closely associated with various neurological disorders such as depression, Parkinson's disease, and epilepsy. However, conventional detection techniques such as microdialysis coupled with liquid chromatography are constrained by limited spatiotemporal resolution and inherent invasiveness, largely due to NE's low concentration, rapid metabolism, and complex distribution in vivo. These limitations make real-time, in situ dynamic monitoring particularly challenging. In recent years, fluorescence and bioluminescence probe technologies, founded on molecular recognition or self-assembly strategies, have enabled notable advances in the in situ detection and imaging of NE, owing to their superior spatiotemporal resolution, favorable biocompatibility, and versatile design. This review summarizes several representative studies in the field, covering probe design principles, response mechanisms, analytical performance, and biological applications. It also highlights emerging frontiers such as subcellular localization, in vivo dynamic imaging, millisecond-scale monitoring, multitarget cooperative recognition, and integrated diagnosis and therapy. These technologies have deepened our understanding of the spatiotemporal dynamics of NE in physiological and pathological processes, while also providing powerful tools for mechanistic research, early diagnosis, and precise treatment of neuropsychiatric disorders.