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

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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.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgments

We thank members of the Lu laboratory for helpful discussions and comments. This work was 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), and International Science and Technology Cooperation Base of Guangdong Province (2019A050505008).

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Author notes

  1. Yefei Chen, **gyi Wang, and **g Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518027, China

    Yefei Chen, **g Liu, ** Lin, **yao Nie, Qi Yue, Chunshan Deng, Ji Dai & Zhonghua Lu

  2. University of Chinese Academy of Sciences, Bei**g, 100049, China

    **gyi Wang, Jianbang Lin, Chunshan Deng, Ji Dai & Zhonghua Lu

  3. 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

    Chunshan Deng, Ji Dai & Zhonghua Lu

  4. 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

    Chunshan Deng, Ji Dai & Zhonghua Lu

  5. Biomedical Research Institute, Hubei University of Medicine, Shiyan, 442000, China

    Yuantao Li

  6. Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China

    Zhonghua Lu

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  1. Yefei Chen
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Correspondence to **aofei Qi, Ji Dai or Zhonghua Lu.

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Y.C., J.W., J. Liu, J. Lin, J.D., and Z.L. are co-inventors on a patent that is being filed for this technology.

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Chen, Y., Wang, J., Liu, J. et al. A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys. Neurosci. Bull. 40, 90–102 (2024). https://doi.org/10.1007/s12264-023-01091-0

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