Summary: Researchers induced arm movements in macaque monkeys by using optogenetics to target the motor cortex.
Source: National Institutes of Natural Sciences
Optogenetics is a recently developed technique that can control cellular functions by illuminating lights to the cells in which light-sensitive proteins are expressed by gene transfer. Optogenetics enabled us to activate or inhibit a specific population of neuronal cells and revolutionized stimulation methods. It has now become an indispensable tool for investigating brain functions. So far, most studies using this technique have been performed in rodents, whereas trials to modify behaviors in monkeys have ended up in failure, except for a few studies targeting eye movements.
The research group lead by Professor Atsushi Nambu at National Institute for Physiological Sciences and Professor Hajime Mushiake at Tohoku University, has succeeded in inducing arm movements in Japanese macaque monkeys by using optogenetics. This study will be published in Nature Communications.
First, the research team developed an adeno-associated viral vector that effectively expresses a light-sensitive protein, channelrhodopsin. The team injected the viral vector exactly into the arm region of the motor cortex in which electrical stimulation can induce clear arm movements. The team also developed an optrode that can record neuronal activity and apply light and electrical stimulation separately. The optrode was inserted into the motor cortex, and light stimulation was applied. Light stimulation through the optrode effectively activated neuronal cells expressing channelrhodopsin, and induced muscle activity and clear arm movements, which are comparable to those induced by electrical stimulation through the same optrode.
This study has opened the door to optogenetic studies in non-human primates and toward clinical application in human patients, such as optical deep brain stimulation (DBS).
Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex
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 generate an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and inject into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 is strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induces prominent cortical activity: Even single-pulse, short-duration oICMS evokes long-lasting repetitive firings of cortical neurons. In addition, oICMS elicits distinct forelimb movements and muscle activity, which are comparable to those elicited by conventional electrical ICMS. The present study removes obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.