Longitudinal neural connection detection using a ferritin-encoding adeno-associated virus vector and in vivo MRI...

Area of Science:

• Neuroscience
• Medical Imaging
• Molecular Biology

Background:

• Investigating neural circuits is crucial for understanding brain function and disorders.
• Current methods using fluorescent imaging have limited depth, hindering whole-brain analysis in vivo.
• Existing techniques struggle to provide a comprehensive view of neural connections in living organisms.

Purpose of the Study:

• To develop a noninvasive, whole-brain imaging technique for mapping neural circuits in vivo.
• To combine MRI with a hypotoxic adeno-associated virus (AAV) vector for neural circuit investigation.
• To enable longitudinal detection of viral spread and neural connections in living animals.

Main Methods:

• Utilized MRI combined with an engineered adeno-associated virus (AAV2-retro) vector encoding ferritin protein.
• Injected the ferritin-encoding virus vector (rAAV2-retro-CAG-Ferritin) into the caudate putamen (CPu) of mice.
• Analyzed MRI contrast changes and T2 relaxation times to identify infected regions and viral spread over time.

Main Results:

• Significant MRI contrast changes were observed in regions including the prefrontal cortex (PFC), hippocampus (HIP), insular cortex (Ins), and basolateral amygdala (BLA).
• Ferritin expression in these regions was confirmed using ex vivo fluorescence imaging.
• Demonstrated that T2 relaxation time changes correlate with viral spread, enabling longitudinal detection.

Conclusions:

• The developed in vivo MRI technique offers a novel, noninvasive approach to map whole-brain neural circuits.
• This method allows for longitudinal observation of viral infection processes and neural connections in living animals.
• The technique holds potential for advancing the study of brain function, psychiatric disorders, and therapeutic interventions.