Combining long-term circuit mapping and network transcriptomics with SiR-N2c

Area of Science:

• Circuit neuroscience
• Neurobiology
• Genomics

Background:

• Neural network mapping and single-cell genomics are merging.
• Monosynaptic rabies viruses are promising for combining circuit mapping with 'omics' approaches.
• Limitations include viral cytotoxicity, immunogenicity, and altered gene expression.

Purpose of the Study:

• To develop a rabies virus that minimizes cytotoxicity and immune response.
• To enable accurate gene expression profiling in mapped neural circuits.
• To facilitate single-cell genomic characterization of neural networks.

Main Methods:

• Genomic modification of the CVS-N2c rabies strain to create a self-inactivating virus (SiR-N2c).
• Application of SiR-N2c for neural circuit tracing.
• Analysis of gene expression profiles in infected neurons and surrounding cells.

Main Results:

• SiR-N2c demonstrated reduced cytotoxicity and minimal alteration of cellular transcriptional profiles.
• The modified virus significantly dampened innate and acquired immune responses.
• Enabled open-ended interventions on neural networks for genetic characterization.

Conclusions:

• SiR-N2c effectively overcomes key limitations of previous rabies virus systems.
• This tool facilitates the integration of circuit neuroscience and single-cell genomics.
• Paves the way for advanced neural network analysis and genetic profiling.