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. 2020 Dec 23;108(6):1075-1090.e6.
doi: 10.1016/j.neuron.2020.09.027. Epub 2020 Oct 19.

An Open Resource for Non-human Primate Optogenetics

Sébastien Tremblay  1 Leah Acker  2 Arash Afraz  3 Daniel L Albaugh  4 Hidetoshi Amita  5 Ariana R Andrei  6 Alessandra Angelucci  7 Amir Aschner  8 Puiu F Balan  9 Michele A Basso  10 Giacomo Benvenuti  11 Martin O Bohlen  12 Michael J Caiola  4 Roberto Calcedo  13 James Cavanaugh  14 Yuzhi Chen  11 Spencer Chen  11 Mykyta M Chernov  15 Andrew M Clark  7 Ji Dai  16 Samantha R Debes  6 Karl Deisseroth  17 Robert Desimone  2 Valentin Dragoi  6 Seth W Egger  2 Mark A G Eldridge  18 Hala G El-Nahal  12 Francesco Fabbrini  19 Frederick Federer  7 Christopher R Fetsch  20 Michal G Fortuna  21 Robert M Friedman  15 Naotaka Fujii  22 Alexander Gail  23 Adriana Galvan  4 Supriya Ghosh  24 Marc Alwin Gieselmann  25 Roberto A Gulli  26 Okihide Hikosaka  5 Eghbal A Hosseini  2 Xing Hu  4 Janina Hüer  21 Ken-Ichi Inoue  27 Roger Janz  6 Mehrdad Jazayeri  2 Rundong Jiang  28 Niansheng Ju  28 Kohitij Kar  2 Carsten Klein  29 Adam Kohn  30 Misako Komatsu  22 Kazutaka Maeda  5 Julio C Martinez-Trujillo  31 Masayuki Matsumoto  32 John H R Maunsell  24 Diego Mendoza-Halliday  2 Ilya E Monosov  33 Ross S Muers  25 Lauri Nurminen  7 Michael Ortiz-Rios  34 Daniel J O'Shea  35 Stéphane Palfi  36 Christopher I Petkov  25 Sorin Pojoga  6 Rishi Rajalingham  2 Charu Ramakrishnan  37 Evan D Remington  2 Cambria Revsine  38 Anna W Roe  39 Philip N Sabes  40 Richard C Saunders  18 Hansjörg Scherberger  23 Michael C Schmid  41 Wolfram Schultz  42 Eyal Seidemann  11 Yann-Suhan Senova  36 Michael N Shadlen  43 David L Sheinberg  44 Caitlin Siu  7 Yoland Smith  4 Selina S Solomon  8 Marc A Sommer  12 John L Spudich  45 William R Stauffer  46 Masahiko Takada  47 Shiming Tang  28 Alexander Thiele  25 Stefan Treue  23 Wim Vanduffel  48 Rufin Vogels  19 Matthew P Whitmire  11 Thomas Wichmann  4 Robert H Wurtz  14 Haoran Xu  2 Azadeh Yazdan-Shahmorad  49 Krishna V Shenoy  50 James J DiCarlo  2 Michael L Platt  51
Affiliations

An Open Resource for Non-human Primate Optogenetics

Sébastien Tremblay et al. Neuron. .

Abstract

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.

Keywords: Gene therapy; Monkey; Monkeys; Non-human primates; Nonhuman primates; Open Science; Optical control; Optogenetic; Optogenetics; Viral vectors.

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Conflict of interest statement

Declaration of Interests S. Palfi received consulting honorarium from OxfordBiomedica. K.V.S. is a consultant for Neuralink and is on the scientific advisory board for CTRL-Labs, MIND-X, Inscopix, and Heal. These entities did not support this work. P.N.S. has financial interests in Neuralink, a company developing clinical therapies using brain stimulation.

Figures

Figure 1.
Figure 1.. Number of published papers using optogenetics.
Number of new published articles per year using optogenetics in rodents (red) and in NHP (blue) since year of first species-specific publication. Review articles are excluded. Inset shows the same data but includes only NHP studies.
Figure 2.
Figure 2.. Flow chart of laboratories’ participation in the NHP Optogenetics Open Database.
A “No answer” was considered after three repeated failed attempts at contacting the investigator. Overall, the response of the community was overwhelmingly positive.
Figure 3.
Figure 3.. Popularity of various resources for NHP optogenetics.
Frequency of each NHP species (A), viral vector (B), genetic promoter (C), opsin gene (D), and reporter protein (E) across the entire database. One entry corresponds to one injection. Variants with less than 10 entries were grouped in the category “Other”. “Macaque” refers to entries where the species of macaque was not specified. “AAV9; AAV5” refers to a mix of both capsids in the same viral solution.
Figure 4.
Figure 4.. Outcome of optogenetics experiments in NHP.
A) Proportion of injections that led to a strong physiological effect, a weak or mixed effect, or no effect. A weak or mixed effect was defined as per the investigators’ comments reporting either weak, unreliable, or mixed physiological response. White numbers represent absolute number of injection tests. B & C) Same as in A, but for anatomical and behavioral analyses, respectively. D) Left: Proportion of injections that led to at least one strong outcome across all three possible outcome modalities (physiology, anatomy, or behavior). Right: This bar also includes injections that led to at least one weak or mixed outcome (or better), across all three outcome modalities.
Figure 5.
Figure 5.. Success rate of experiments as a function of optogenetics resources used.
A) Percentage of injections that led to at least one strong effect across the three outcome modalities, as a function of NHP species. B) Same as in A, as a function of viral vector. C) Proportion of experiments that acquired their viral vector from each Vector Core. D) Same as in A, as a function of genetic promoter. E) Same as in A, as a function of opsin gene. F) Same as in A, as a function of reporter protein. Dotted bars represent variables that had low sample size in the database (i.e. tested in fewer than 20 injections or in fewer than 5 animals).
Figure 6.
Figure 6.. Surgical and injection methods used across experiments.
A) Proportion of each surgical method used to access the brain parenchyma for injection purposes. B) Histogram of the rate of injection of the viral solution across all experiments. C) Histogram of the volume of viral solution injected across all experiments.
Figure 7.
Figure 7.. Publication bias in NHP optogenetics studies.
Comparison of the rate of successful (strong effect) and unsuccessful (no effect) experiments across the published and unpublished entries in the database.

References

    1. Acker L, Pino EN, Boyden ES, and Desimone R (2016). FEF inactivation with improved optogenetic methods. Proceedings of the National Academy of Sciences 113, E7297–E7306. - PMC - PubMed
    1. Afraz A, Boyden ES, and DiCarlo JJ (2015). Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination. Proceedings of the National Academy of Sciences 112, 6730–6735. - PMC - PubMed
    1. Amita H, Kim HF, Inoue K-I, Takada M, and Hikosaka O (2020). Optogenetic manipulation of a value-coding pathway from the primate caudate tail facilitates saccadic gaze shift. Nat Commun 1–13. - PMC - PubMed
    1. Andrei AR, Pojoga S, Janz R, and Dragoi V (2019). Integration of cortical population signals for visual perception. Nat Commun 10, 3832–13. - PMC - PubMed
    1. Bjornson-Hooper ZB, Fragiadakis GK, Spitzer MH, Madhireddy D, McIlwain D, and Nolan GP (2019). A comprehensive atlas of immunological differences between humans, mice and non-human primates. bioRxiv 173173, 1166–12. - PMC - PubMed

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