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

Yefei Chen, Jingyi Wang, Jing Liu, Jianbang Lin, Yunping Lin, Jinyao Nie, Qi Yue, Chunshan Deng, Xiaofei Qi, Yuantao Li, Ji Dai, Zhonghua Lu
Author Information
  1. Yefei Chen: Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518027, China. ORCID
  2. Jingyi Wang: 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. Jing Liu: Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518027, China.
  4. Jianbang Lin: 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.
  5. Yunping Lin: 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.
  6. Jinyao Nie: 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.
  7. Qi Yue: 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.
  8. Chunshan Deng: 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.
  9. Xiaofei Qi: Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518027, China. xiaofeiqi@smu.edu.cn. ORCID
  10. Yuantao Li: Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, 518027, China.
  11. Ji Dai: 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. ji.dai@siat.ac.cn. ORCID
  12. Zhonghua Lu: 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. zh.lu@siat.ac.cn. ORCID

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

References

  1. J Virol. 2008 Jun;82(12):5887-911 [PMID: 18400866]
  2. Neurosci Bull. 2023 Dec;39(12):1749-1761 [PMID: 36920645]
  3. Neuroscientist. 2018 Oct;24(5):526-539 [PMID: 28874078]
  4. Neuron. 2016 Oct 19;92(2):372-382 [PMID: 27720486]
  5. Front Neuroanat. 2019 Nov 26;13:93 [PMID: 31849618]
  6. Curr Biol. 2014 Jan 6;24(1):63-69 [PMID: 24332543]
  7. Virology. 2000 Dec 20;278(2):301-8 [PMID: 11118354]
  8. J Neurosci. 2015 Jun 24;35(25):9265-80 [PMID: 26109652]
  9. Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):27053-27062 [PMID: 31818949]
  10. Neuron. 2019 Mar 6;101(5):839-862 [PMID: 30844402]
  11. Nat Neurosci. 2016 Feb;19(2):335-46 [PMID: 26727548]
  12. Nature. 2015 Aug 6;524(7563):88-92 [PMID: 26131933]
  13. Neuron. 2000 Oct;28(1):41-51 [PMID: 11086982]
  14. Nature. 2019 Nov;575(7781):195-202 [PMID: 31666704]
  15. Nature. 2010 Jul 29;466(7306):622-6 [PMID: 20613723]
  16. Nature. 2016 Apr 7;532(7597):103-6 [PMID: 27001694]
  17. Nature. 2016 Feb 4;530(7588):108-12 [PMID: 26814968]
  18. J Neurosci Methods. 2020 Nov 1;345:108859 [PMID: 32668316]
  19. Eur J Neurosci. 2020 Dec;52(12):4824-4839 [PMID: 33113247]
  20. Innovation (Camb). 2022 Dec 05;4(1):100358 [PMID: 36583100]
  21. Nat Rev Neurosci. 2017 Sep;18(9):530-546 [PMID: 28775344]
  22. Nature. 2021 Oct;598(7879):174-181 [PMID: 34616072]
  23. Neuron. 2020 Jul 8;107(1):38-51.e8 [PMID: 32353253]
  24. Neurosci Bull. 2022 Nov;38(11):1383-1396 [PMID: 35578093]
  25. Neuron. 2018 Apr 18;98(2):256-281 [PMID: 29673479]
  26. Curr Opin Neurobiol. 2018 Jun;50:109-118 [PMID: 29471215]
  27. Neurosci Bull. 2021 Apr;37(4):461-477 [PMID: 33373031]
  28. J Neurosci. 2019 Apr 24;39(17):3234-3248 [PMID: 30782975]
  29. Sci Rep. 2020 Apr 24;10(1):6970 [PMID: 32332773]
  30. J Virol. 2000 Mar;74(6):2777-85 [PMID: 10684294]
  31. Neurosci Bull. 2022 Dec;38(12):1508-1518 [PMID: 36136267]
  32. Hum Gene Ther. 2020 Nov;31(21-22):1155-1168 [PMID: 32940068]
  33. Neuron. 2015 Dec 16;88(6):1253-1267 [PMID: 26671462]
  34. Brain. 2018 Jul 1;141(7):2014-2031 [PMID: 29788236]
  35. Nat Neurosci. 2016 Aug 26;19(9):1123-30 [PMID: 27571191]
  36. Neuron. 2007 Mar 1;53(5):639-47 [PMID: 17329205]
  37. Neuron. 2011 Dec 22;72(6):938-50 [PMID: 22196330]

MeSH Term

Animals
Haplorhini
Axons
Motor Neurons
Interneurons
Macaca
Dependovirus
Genetic Vectors

Word Cloud

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