Convection Enhanced Delivery of Optogenetic Adeno-associated Viral Vector to the Cortex of Rhesus Macaque Under Guidance of Online MRI Images

作者： Karam Khateeb1,2, Devon J. Griggs2,3, Philip N. Sabes4, Azadeh Yazdan-Shahmorad1,2,3,4 1Departments of Bioengineering,University of Washington, 2Washington National Primate Research Center, 3Department of Electrical and Computer Engineering,University of Washington, 4Department of Physiology and Center for Integrative Neuroscience,University of California, San Francisco

简介：

Overview

This study demonstrates MR-guided convection enhanced delivery (CED) of viral vectors in the macaque brain, facilitating large-scale optogenetic manipulation of neural activity. By combining CED with MRI technology, researchers achieve efficient and widespread optogenetic expression across cortical areas.

Key Study Components

Area of Science

• Neuroscience
• Optogenetics
• Biomedical Imaging

Background

• Convection enhanced delivery (CED) is a method for infusing substances directly into target brain regions.
• Optogenetic techniques allow researchers to manipulate neuronal activity through light-sensitive proteins.
• Combining CED with MRI facilitates precise targeting and tracking of the infusions.

Purpose of Study

• To describe an efficient, simplified approach for delivering viral vectors into the cortex.
• To enable manipulation of neural activity across large brain areas in non-human primates.
• To enhance understanding of complex neural computations and behaviors.

Methods Used

• The study employed MR-guided convection enhanced delivery for infusing viral vectors.
• The biological model utilized was the macaque brain.
• Standard surgical procedures for chamber implantation were followed, allowing for precise infusion.
• Real-time MRI monitoring was implemented during infusion to ensure accurate delivery.
• Histological analyses were conducted to assess optogenetic expression following viral vector infusion.

Main Results

• The method achieved widespread optogenetic expression across large cortical regions.
• Histological analyses indicated successful delivery and expression of the viral vectors, evidenced by significant EYFP reporter expression.
• Online MRI imaging provided critical feedback for monitoring infusion progress and placement accuracy.

Conclusions

• This study demonstrates the potential of MR-guided CED for efficiently achieving optogenetic manipulation in large brain regions.
• The results enable further exploration of neural mechanisms and behaviors.
• Implications of this research extend to applications in understanding complex neural circuitry and functions in primate models.

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