A novel technology for in vivo detection of cell type-specific neural connection with AQP1-encoding rAAV2-retro vector and metal-free MRI
Ning Zheng, Li Mei, Yang Wu, Challika Kaewborisuth, Zhen Li, Zhu Gui, Jinfeng Wu, Aoling Cai, Kangguang Lin, Kuan‐Pin Su, Hong‐Bing Xiang, Xuebi Tian, Anne Manyande, Fuqiang Xu, Jie Wang
Abstract
A mammalian brain contains numerous neurons with distinct cell types for complex neural circuits. Virus-based circuit tracing tools are powerful in tracking the interaction among the different brain regions. However, detecting brain-wide neural networks in vivo remains challenging since most viral tracing systems rely on postmortem optical imaging. We developed a novel approach that enables in vivo detection of brain-wide neural connections based on metal-free magnetic resonance imaging (MRI). The recombinant adeno-associated virus (rAAV) with retrograde ability, the rAAV2-retro, encoding the human water channel aquaporin 1 (AQP1) MRI reporter gene was generated to label neural connections. The mouse was micro-injected with the virus at the Caudate Putamen (CPU) region and subjected to detection with Diffusion-weighted MRI (DWI). The prominent structure of the CPU-connected network was clearly defined. In combination with a Cre-loxP system, rAAV2-retro expressing Cre-dependent AQP1 provides a CPU-connected network of specific type neurons. Here, we established a sensitive, metal-free MRI-based strategy for in vivo detection of cell type-specific neural connections in the whole brain, which could visualize the dynamic changes of neural networks in rodents and potentially in non-human primates.