An Open Resource for Non-human Primate Optogenetics

Tremblay, Sébastien; Acker, Leah; Afraz, Arash; Albaugh, Daniel L.; Amita, Hidetoshi; Andrei, Ariana R.; Angelucci, Alessandra; Aschner, Amir; Balan, Puiu; Basso, Michele A.; Benvenuti, Giacomo; Bohlen, Martin O.; Caiola, Michael; Calcedo, Roberto; Cavanaugh, James; Chen, Yuzhi; Chen, Spencer; Chernov, Mykyta M.; Clark, Andrew M.; Dai, Ji; Debes, Samantha R.; Deisseroth, Karl; Desimone, Robert; Dragoi, Valentin; Egger, Seth W.; Eldridge, Mark; El-Nahal, Hala G; Fabbrini, Francesco; Federer, Frederick; Fetsch, Christopher R.; Fortuna, Michal G.; Friedman, Robert M.; Fujii, Naotaka; Gail, Alexander; Galván, Adriana; Ghosh, Supriya; Gieselmann, Marc Alwin; Gulli, Roberto A.; Hikosaka, Okihide; Hosseini, Eghbal A.; Hu, Xing; Hüer, Janina; Inoue, Ken; Janz, Roger; Jazayeri, Mehrdad; Jiang, Rundong; Ju, Niansheng; Kar, Kohitij; Klein, C.; Kohn, Adam; Komatsu, Misako; Maeda, Kaori; Martinez‐Trujillo, Julio; Matsumoto, Masayuki; Maunsell, John H. R.; Mendoza-Halliday, Diego; Monosov, Ilya E.; Muers, Ross S.; Nurminen, Lauri; Ortiz-Rios, Michael; O’Shea, Daniel J.; Palfi, Stéphane; Petkov, Christopher I.; Pojoga, Sorin; Rajalingham, Rishi; Ramakrishnan, Charu; Remington, Evan D.; Revsine, Cambria; Roe, Anna Wang; Sabes, Philip N.; Saunders, Richard C.; Scherberger, Hansjörg; Schmid, Michael C.; Schultz, Wolfram; Seidemann, Eyal; Senova, Yann Suhan; Shadlen, Michael N.; Sheinberg, David L.; Siu, Caitlin; Smith, Yoland; Solomon, Selina S.; Sommer, Marc A.; Spudich, John L.; Stauffer, William R.; Takada, Masahiko; Tang, Shiming; Thiele, Alexander; Treue, Stefan; Vanduffel, Wim; Vogels, Rufin; Whitmire, Matthew P.; Wichmann, Thomas; Wurtz, Robert H.; Xu, Haoran; Yazdan-Shahmorad, Azadeh; Shenoy, Krishna V.; DiCarlo, James J.; Platt, Michael L.

doi:10.1016/j.neuron.2020.09.027

Cited by 86 publications

(60 citation statements)

References 95 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recognizing that further research is needed to determine the origin of the low success rates, it is nevertheless the case that at the moment success in obtaining strong effects across multiple functional outcomes when pursuing optogenetics in NHPs amounts to flipping a coin. This warrants a very different conclusion from the one that a reader might reasonably draw after reading the survey by Tremblay et al (2020).…”

Section: Resultsmentioning

confidence: 80%

“…These approaches have led to an explosion of publications on circuit mechanisms of behavior, primarily in mice, but the implementation of these methods in the nonhuman primate (NHP) brain has lagged substantially. In a recent paper published in Neuron (Tremblay et al, 2020), a large team of neuroscientists introduced an openly available resource detailing published and unpublished studies that use optogenetic techniques to manipulate the NHP brain. The effort reflects contributions from 45 research laboratories, with 1042 individual data points included (552 previously unpublished) representing experiments in 198 monkeys.…”

Section: A Pragmatic Reevaluation Of the Efficacy Of Nonhuman Primatementioning

confidence: 99%

“…The resource detailed in Tremblay et al (2020) aggregates an enormous amount of technical expertise on neurosurgical placement of viral vectors in the NHP brain, a substantial contribution to the field. Moreover, meta-and open science efforts in NHP neuroscience are critical and until very recently, very rare.…”

Section: A Pragmatic Reevaluation Of the Efficacy Of Nonhuman Primatementioning

confidence: 99%

See 2 more Smart Citations

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry

Bliss‐Moreau

Costa

Baxter

2020

Preprint

View full text Add to dashboard Cite

A recent paper published in Neuron by Tremblay et al. (2020) introduces an openly available resource detailing published and unpublished studies using optogenetics to manipulate the nonhuman primate (NHP) brain. The open science efforts of the team are important and rare in NHP neuroscience, but the conclusions drawn about the success rate of optogenetics in the NHP brain are problematic for quantitative and theoretical reasons. Quantitively, the analyses in the paper are performed at a level relevant to the rodent but not NHP brain (single injections) and individual injections are clustered within a few monkeys and a few studies. Theoretically, the report makes strong claims about the importance of the technology for disease related functional outcomes, but behavior was not widely tested. The original article reports a 91% success rate for optogenetic experiments in NHPs based on the presence of any outcome (histological, physiological, or behavioral outcomes) after an injection of viral vectors. Reanalysis of the data clustered at the level of brain region and animal with a modified definition of success that included a behavioral and biological effect reveals that the rate of success was approximately 62.5%, and only 53.1% for strong outcomes, in experiments that attempted to measure a behavioral and a biological effect. Only 6% of the experiments in the total database successfully achieved histological, physiological, and behavioral endpoints. This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in “the service of patients with neurological or psychiatric conditions”.

show abstract

Section: Resultsmentioning

confidence: 80%

Section: A Pragmatic Reevaluation Of the Efficacy Of Nonhuman Primatementioning

confidence: 99%

Section: A Pragmatic Reevaluation Of the Efficacy Of Nonhuman Primatementioning

confidence: 99%

See 1 more Smart Citation

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry

Bliss‐Moreau

Costa

Baxter

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Future studies that combine opto-tagging in monkeys with simultaneous application of WaveMAP and other waveform classification methods will allow us to more precisely link our putative cell classes to function 120 and do so in vivo. NHP optogenetics is slowly advancing and efforts in many research groups around the world are producing new methods for in vivo optogenetics 121 . We expect future experiments using the promising new mDlx 122 and h56d 123 promoter sequences to selectively opto-tag inhibitory neurons or PV + neurons directly 124 will greatly benefit validation of these derived cell classes.…”

Section: Discussionmentioning

confidence: 99%

Non-linear Dimensionality Reduction on Extracellular Waveforms Reveals Cell Type Diversity in Premotor Cortex

Lee

Balasubramanian²,

Tsolias

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Cortical circuits involved in decision-making are thought to contain a large number of cell types—each with different physiological, functional, and laminar distribution properties—that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features, such as trough to peak duration of extracellular spikes, to identify putative cell types these but can only capture a small amount of variation. Here, we develop a new method (WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while also revealing undocumented diversity. These clusters exhibit distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. By revealing additional cell type diversity, WaveMAP facilitates a more nuanced understanding of how the dynamics of cell types unfolds across cortical layers during decision-making.

show abstract

“…Our MMAD in combination with our previously presented chronic interfaces (Yazdan-Shahmorad et al ., 2015, 2016; Griggs et al ., 2019) equip us for a variety of research pursuits. Moving forward, we plan to capitalize on our previous optogenetic (Ledochowitsch et al ., 2015; Yazdan-Shahmorad et al ., 2015, 2016, 2018b, 2018a, 2018c; Khateeb et al ., 2019a; Ojemann et al ., 2020; Tremblay et al ., 2020) and imaging (Khateeb et al ., 2019b; Macknik et al ., 2019) experience as we pioneer the experimental spaces unveiled by the merging of large-scale ECoG and large-scale optical access to the NHP cortex. The synergistic power of these technologies poise us to build on our past work investigating neural plasticity (Yazdan-Shahmorad et al ., 2018a; Bloch et al ., 2019) as we study large-scale, chronic neural phenomena including neural disease, damage, and recovery.…”

Section: Discussionmentioning

confidence: 99%

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex

Griggs

Khateeb

Zhou

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Objective. Non-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery. Approach. We present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (~3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side and in vivo with macaques to validate the utility of our MMAD. Main results. Using our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and via in vivo imaging of blood flow from the underlying microvasculature using optical coherence tomography angiography. Significance. Our results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.

show abstract

An Open Resource for Non-human Primate Optogenetics

Cited by 86 publications

References 95 publications

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry

Non-linear Dimensionality Reduction on Extracellular Waveforms Reveals Cell Type Diversity in Premotor Cortex

Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex

Contact Info

Product

Resources

About