A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys
Yefei Chen1,2 · Jingyi Wang2,3 · Jing Liu1,2 · Jianbang Lin2,3 · Yunping Lin2 · Jinyao Nie2 · Qi Yue2 · Chunshan Deng2,3,4,5 · Xiaofei Qi1 · Yuantao Li1,6 · Ji Dai2,3,4,5 · Zhonghua Lu2,3,4,5,71 Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen 518027, China
2 Shenzhen Technological Research Center for Primate Translational Medicine, Shenzhen Key Laboratory for Molecular Biology of Neural Development, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
5 Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
6 Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China
7 Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Abstract
Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Keywords
Retrograde AAV; Capsid variant; Cortical projection neuron; Optogenetics; Monkey
