New optical methods for detecting monoamine neuromodulators

Monoamine neuromodulators such as dopamine, norepinephrine, serotonin (5-HT), octopamine, and tyramine are signaling molecules in the nervous system, where they play critical roles in both health and disease. Given the complex spatiotemporal dynamics, similar structural features, and multiple receptors, studying their dynamics has been limited using conventional methods such as microdialysis and electrochemistry. However, recent advances in optics have facilitated the development of imaging-based detection methods. In this review, we summarize current detecting approaches for specific monoamines, emphasizing their design strategies, detection properties, applications, and limitations. We highlight the genetically encoded GPCR-based sensors for DA and NE, which have high signal-to-noise ratio, selectivity and can be used in vivo in different living organisms. Finally, we discuss the potential for using this approach to generate new neuromodulator sensors with nonoverlapping spectra, which will ultimately pave the way for studying the interplay among various neuromodulators and neurotransmitters.