Dissecting mammalian cortical circuit development at single-cell resolution using inducible barcoded rabies virus

Area of Science:

• Neuroscience
• Genomics
• Developmental Biology

Background:

• Brain circuits are essential for function, but their development is poorly understood.
• Neurodevelopmental disorders are linked to improper circuit formation.
• Current methods for studying neural circuits lack scale, temporal control, and molecular detail.

Purpose of the Study:

• To develop a novel tool for temporal-controlled, high-throughput circuit analysis at single-cell resolution.
• To investigate the developmental trajectory of mouse cortical circuits.
• To understand the molecular mechanisms underlying circuit formation and potential dysfunction.

Main Methods:

• Development of an inducible barcoded rabies virus (ibRV) for temporal labeling.
• Application of ibRV for circuit tracing in developing mouse brains.
• Utilizing single-cell genomics and spatial transcriptomics for readout.
• Construction of in silico circuit models for functional interrogation.

Main Results:

• ibRV enables temporal-controlled, high-throughput, single-cell resolution circuit mapping.
• Characterization of developmental connectivity patterns in mouse cortical circuits.
• Identification of molecular cascades involved in circuit formation.
• Development of computational models to study circuit function and dysfunction.

Conclusions:

• ibRV is a powerful new tool for dissecting neuronal circuit development and disease mechanisms.
• Provides insights into mammalian brain development at unprecedented resolution.
• Facilitates the study of neurodevelopmental disorders by analyzing circuit changes over time.