New rabies viral resources for multi-scale neural circuit mapping

Area of Science:

• Neuroscience
• Molecular Biology
• Biotechnology

Background:

• Neural circuit connectomics requires integrating data across diverse imaging scales.
• Existing viral tools have limitations in resolution and multimodal capabilities for comprehensive circuit mapping.

Purpose of the Study:

• To develop novel recombinant rabies virus (RV) vectors for enhanced multi-scale and multi-modal neural circuit mapping.
• To expand the capabilities of RV-mediated tracing for detailed connectomic analysis.

Main Methods:

• Development of 20 new recombinant rabies virus (RV) vectors.
• Incorporation of improved fluorescent proteins and subcellular targeting.
• Design of RVs encoding reporters for correlative electron microscopy (EM) and fluorescence microscopy (FM).

Main Results:

• Demonstrated utility in detecting microstructural changes in neurons in aging and Alzheimer's disease models.
• Enabled live imaging of neuronal activity using calcium indicators.
• Facilitated automated measurement of infected neurons and dual EM/mesoscale imaging.

Conclusions:

• The new RV variants significantly enhance the scale and power of rabies virus-mediated neural labeling.
• These tools provide unprecedented capabilities for neural circuit mapping across multiple imaging scales.
• The developed vectors are valuable for studying neural circuits in both health and disease states.