Dissecting the pathological basis of brain disorders with genetically encoded fluorescent neurochemical sensors

Brain disorders exhibit profound spatiotemporal complexity, involving intricate disruptions in synaptic transmission and neurochemical signaling. A precise understanding of these dynamic processes is crucial for developing effective therapeutics but remains technically challenging. Genetically encoded fluorescent sensors have emerged as transformative tools to bridge this gap by enabling the real-time monitoring of neurochemical events with high specificity. This review highlights how cutting-edge single-fluorophore biosensors for neurochemicals are being applied to dissect the pathological mechanisms underlying diverse brain disorders. We further outline future frontiers in sensor technology, including data-driven machine learning-guided design, spectral multiplexing, and quantitative fluorescence lifetime imaging. Together, these advances provide a robust and evolving toolkit for elucidating the neurochemical basis of brain disease and guiding next-generation therapeutic strategies.