Designed optogenetic tool for bridging single-neuronal multimodal information in intact animals

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Understanding neuronal cell types and brain circuits requires integrating morphology, function, and molecular data.
• Current methods struggle to map arbitrary neurons in vivo alongside their functional and molecular traits.

Purpose of the Study:

• To develop a system for simple, rapid, and long-term in vivo labeling of entire neuron morphologies.
• To enable multimodal characterization of individual neurons by linking morphology with function and gene expression.

Main Methods:

• Developed a genetically encoded Photo-inducible single-cell labeling (Pisces) system.
• Demonstrated Pisces in intact larval zebrafish for labeling arbitrary neurons.
• Combined Pisces with in vivo calcium imaging and single-cell RNA sequencing/fluorescence in situ hybridization.

Main Results:

• Pisces enables efficient, long-term labeling of complete neuronal morphology in vivo.
• The system facilitates sequential tracing of multiple neurons for projectome mapping.
• Successfully linked neuronal morphology with functional activity and gene expression data.

Conclusions:

• Pisces provides a powerful tool for multimodal single-neuron analysis in vivo.
• This approach advances the creation of single-neuronal multimodal atlases.
• Facilitates deeper understanding of neural circuitries and brain functions.