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Convection Enhanced Delivery of Optogenetic Adeno-associated Viral Vector to the Cortex of Rhesus Macaque Under Guidance of Online MRI Images
Published on: May 23, 2019
Widespread optogenetic expression in macaque cortex obtained with MR-guided, convection enhanced delivery (CED) of
Azadeh Yazdan-Shahmorad1, Nan Tian1, Viktor Kharazia1
1Department of Physiology and Center for Integrative Neuroscience, University of California San Francisco, San Francsico, CA, USA.
Background:
In non-human primate (NHP) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. Previous work has shown that parenchymal delivery of adeno-associated virus (AAV) in the thalamus by convection-enhanced delivery (CED) can lead to large-scale transduction via axonal transport in distal areas including cortex. We used this approach to obtain widespread cortical expression of light-sensitive ion channels.
New Method:
AAV vectors co-expressing channelrhodopsin-2 (ChR2) and yellow fluorescent protein (YFP) genes were infused into thalamus of three rhesus macaques under MR-guided CED. After six to twelve weeks recovery, in vivo optical stimulation and single cell recording in the cortex was carried out using an optrode in anesthetized animals. Post-mortem immunostaining against YFP was used to estimate the distribution and level of expression of ChR2 in thalamus and cortex.
Results:
Histological analysis revealed high levels of transduction in cortical layers. The patterns of expression were consistent with known thalamo-cortico-thalamic circuits. Dense expression was seen in thalamocortiocal axonal fibers in layers III, IV and VI and in pyramidal neurons in layers V and VI, presumably corticothalamic neurons. In addition we obtained reliable in vivo light-evoked responses in cortical areas with high levels of expression.
Comparison With Existing Methods:
Thalamic CED is very efficient in achieving large expressing areas in comparison to convectional techniques both in minimizing infusion time and in minimizing damage to the brain.
Conclusion:
MR-guided CED infusion into thalamus provides a simplified approach to transduce large cortical areas by thalamo-cortico-thalamic projections in primate brain.
