Optogenetics through windows on the brain in the nonhuman primate.

Area of Science:

• Neuroscience
• Genetics
• Biomedical Engineering

Background:

• Optogenetics offers precise control of neuronal activity but faces challenges in nonhuman primates (NHPs).
• The thick, opaque dura mater in NHPs hinders precise viral delivery and optical access for optogenetics.
• Current methods risk brain damage due to large-diameter penetration devices.

Purpose of the Study:

• To overcome limitations of optogenetics in NHPs by developing a novel method for accessing the brain.
• To enable cell-type-specific, temporally precise control of neural circuits in NHPs.
• To facilitate the development of therapies for human neurological and neuropsychiatric diseases.

Main Methods:

• Developed an optically transparent artificial dura to replace the native dura mater in NHPs.
• Utilized fine glass micropipettes for minimally invasive, targeted viral injections through the artificial dura.
• Employed visual monitoring, intrinsic signal imaging, and electrophysiology for assessing optogenetic agent expression and neuronal activity.

Main Results:

• Achieved precise viral delivery and minimal cortical damage using the artificial dura and micropipettes.
• Enabled visual monitoring of optogenetic agent expression.
• Demonstrated targeted photostimulation and simultaneous neuronal activity measurement in both anesthetized and awake NHPs.

Conclusions:

• The artificial dura provides an essential optical window for advanced optogenetics in NHPs.
• This technique significantly improves spatial precision and minimizes damage compared to existing methods.
• The approach is poised to accelerate NHP research and the development of human neurological therapies.