A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys  

作　　者：Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu 

机构地区：[1]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

出　　处：《Neuroscience Bulletin》2024年第1期90-102,共13页神经科学通报（英文版）

基　　金：supported by Ministry of Science and Technology of China(2019YFA0903803 and 2018YFA0801404);National Natural Science Foundation of China(31871090,32000730,81961128019,and 81901397);Shenzhen Science and Technology Innovation Commission(JCYJ20190809171003698,JCYJ202103243001018,JCYJ20180507182505475,and JCYJ20180504165804015);Shenzhen Technological Research Center for Primate Translational Medicine(F-2021-Z99-504979);Youth Innovation Promotion Association(CAS 2017120);Chinese Academy of Sciences International Partnership Program(172644KYSB20170004);China Postdoctoral Science Foundation(2019M653115.);CAS Key Laboratory of Brain Connectome and Manipulation(2019DP173024);Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017);International Science and Technology Cooperation Base of Guangdong Province(2019A050505008).

摘　　要：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 retro-grade AAV capsids have been shown to offer access to cor-tical 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 retro-grade 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.

关 键 词：Retrograde AAV Capsid variant Cortical projection neuron OPTOGENETICS Monkey 

分 类 号：R338[医药卫生—人体生理学]