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Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque

Anil Bollimunta, Samantha R. Santacruz, Ryan W. Eaton, Pei S. Xu, John H. Morrison, Karen A. Moxon, Jose M. Carmena, Jonathan J. Nassi
doi: https://doi.org/10.1101/2020.04.10.996116
Anil Bollimunta
1Inscopix, Inc.; Palo Alto, CA, USA
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Samantha R. Santacruz
2University of Texas at Austin; Austin, TX, USA
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Ryan W. Eaton
3California National Primate Research Center; Davis, CA, USA
4University of California, Davis; Davis, CA, USA
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Pei S. Xu
1Inscopix, Inc.; Palo Alto, CA, USA
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John H. Morrison
3California National Primate Research Center; Davis, CA, USA
4University of California, Davis; Davis, CA, USA
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Karen A. Moxon
3California National Primate Research Center; Davis, CA, USA
4University of California, Davis; Davis, CA, USA
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Jose M. Carmena
5University of California, Berkeley; Berkeley, CA, USA
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Jonathan J. Nassi
1Inscopix, Inc.; Palo Alto, CA, USA
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  • For correspondence: jnassi@inscopix.com
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Summary

A major effort is now underway across the brain sciences to identify, characterize and manipulate mesoscale neural circuits in order to elucidate the mechanisms underlying sensory perception, cognition and behavior. Optical imaging technologies, in conjunction with genetically encoded sensors and actuators, serve as important tools toward these goals, allowing access to large-scale genetically defined neuronal populations. In particular, one-photon miniature microscopes, coupled with genetically encoded calcium indicators and microendoscopic gradient-refractive index (GRIN) lenses, enable unprecedented readout of neural circuit dynamics in cortical and deep subcortical brain regions during active behavior in rodents. This has already led to breakthrough discoveries across a wide array of rodent brain regions and behaviors. However, in order to study the neural circuit mechanisms underlying more complex and clinically relevant human behaviors and cognitive functions, it is crucial to translate this technology to non-human primates. Here, we describe the first successful application of this technology in the rhesus macaque. We identified a viral strategy for robust expression of GCaMP, optimized a surgical protocol for microendoscope GRIN lens insertion, and created a chronic cranial chamber and lens mounting system for imaging in gyral cortex. Using these methods, we demonstrate the ability to perform plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from over 100 genetically-targeted neurons simultaneously in dorsal premotor cortex while the macaque performs a naturalistic motor reach task with the head unrestrained and freely moving. The recorded population of neurons exhibited calcium dynamics selective to the direction of reach, which we show can be used to decode the animal’s trial-by-trial motor behavior. Recordings were stable over several months, allowing us to longitudinally track large populations of individual neurons and monitor their relationship to motor behavior over time. Finally, we demonstrate the ability to conduct simultaneous, multi-site imaging in bilateral dorsal premotor cortices, offering an opportunity to study distributed networks underlying complex behavior and cognition. Together, this work establishes head-mounted microendoscopic calcium imaging in macaque as a powerful new approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.

Highlights First demonstration of head-mounted microendoscopic calcium imaging in behaving macaque.

Surgical protocols developed for preparing the animal for calcium imaging, including virus injections to express GCaMP and chronic implantation of a GRIN lens to enable optical access to gyral cortex.

Proof of concept plug-and-play calcium imaging in behaving macaques with months long stable recording capability allowing populations of individual neurons to be tracked longitudinally.

Bilateral calcium imaging from dorsal premotor cortex exhibited dynamics selective to the animal’s direction of reach and allowed decoding of the animal’s motor behavior

Competing Interest Statement

Anil Bollimunta, Pei Xu and Jonathan Nassi are paid employees of Inscopix, Inc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 13, 2020.
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Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque
Anil Bollimunta, Samantha R. Santacruz, Ryan W. Eaton, Pei S. Xu, John H. Morrison, Karen A. Moxon, Jose M. Carmena, Jonathan J. Nassi
bioRxiv 2020.04.10.996116; doi: https://doi.org/10.1101/2020.04.10.996116
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Head-mounted microendoscopic calcium imaging in dorsal premotor cortex of behaving rhesus macaque
Anil Bollimunta, Samantha R. Santacruz, Ryan W. Eaton, Pei S. Xu, John H. Morrison, Karen A. Moxon, Jose M. Carmena, Jonathan J. Nassi
bioRxiv 2020.04.10.996116; doi: https://doi.org/10.1101/2020.04.10.996116

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