2019bioRxiv (Cold Spring Harbor Laboratory)Open access

Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex

Hidenori Watanabe, Hiromi Sano, Satomi Chiken, Kenta Kobayashi, Yuko Fukata, Masaki Fukata, Hajime Mushiake, Atsushi Nambu

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Abstract

Abstract Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the human brain, application of optogenetics to non-human primates is still limited. In the present study, we generated an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and injected into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 was strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induced prominent cortical activity: Even single-pulse, short duration oICMS evoked long-lasting repetitive firings of cortical neurons. In addition, oICMS elicited distinct forelimb movements and muscle activity, which were comparable to those elicited by conventional electrical ICMS. The present study removed obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.

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Abstract Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the human brain, application of optogenetics to non-human primates is still limited. In the present study, we generated an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and injected into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 was strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induced prominent cortical activity: Even single-pulse, short duration oICMS evoked long-lasting repetitive firings of cortical neurons. In addition, oICMS elicited distinct forelimb movements and muscle activity, which were comparable to those elicited by conventional electrical ICMS. The present study removed obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.

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Available abstract

Abstract Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the human brain, application of optogenetics to non-human primates is still limited. In the present study, we generated an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and injected into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 was strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induced prominent cortical activity: Even single-pulse, short duration oICMS evoked long-lasting repetitive firings of cortical neurons. In addition, oICMS elicited distinct forelimb movements and muscle activity, which were comparable to those elicited by conventional electrical ICMS. The present study removed obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.

Key concepts: Optogenetics, Forelimb, Neuroscience, Microstimulation, Macaque, Motor cortex, Channelrhodopsin, Stimulation

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