Correlative Imaging Platform Linking Taste Cell Function to Molecular Identity

Understanding the physiology of taste cells requires multifaceted cellular information, ranging from gene expression to functional responses. Various experimental approaches are available to obtain each biological information, such as in situ hybridization for gene transcription and in vivo microscopy for functional responses. However, correlative acquisition of genetic and functional information at the single-cell level has not yet been achieved for taste cells, limiting a comprehensive understanding of functional and genetic cell subtypes. Here, we developed a correlative imaging platform to link functional responses of taste cells to their molecular identity. This platform acquires functional imaging data and in situ hybridization or immunofluorescence data from the same region-of-interest in intact taste buds, using near-infrared branding (NIRB) to ensure spatial correspondence between live and fixed tissues. As a proof-of-principle, we demonstrated that sour cells in vivo specifically express the molecular marker, carbonic anhydrase IV (CA4), at both transcriptional and translational levels. Harnessing this platform, we revealed that sweet/umami dual-tuned responses in gustatory nerves are mainly mediated by synaptic input from taste cells co-expressing all taste receptor type 1 (Tas1R) subtypes, suggesting a combinatoric encoding of preferred taste qualities. We anticipate that our correlative platform facilitates a deeper understanding of taste information processing.