Integrating Single Neuronal Multimodal Information in Intact Animals with Designed Optogenetic Tool (PRJCA031958)

Neurons are highly diverse in their molecular profiles, morphological properties and physiological functions. However, integrating these multi-modal datasets has proven challenging due to the lack of efficient single-neuron morphological tracing tools. Here, we developed a genetically encoded Photo-inducible single cell labeling system, Pisces, which enables simple, rapid, efficient and long-term in vivo labeling of the entire morphology of arbitrary neurons in intact zebrafish. Combining Pisces with in vivo calcium imaging permits the mapping of input-output morphological patterns of individual neurons following the delineation of their functional identities. Furthermore, Pisces allows reliable isolation of photo-converted neurons and subsequent identification of their transcriptional profiles. Thus, our study introduces Pisces as a robust optical tool for integrating molecular, structural and functional information at single-cell level in intact organisms.