Optimized large-scale optogenetic interface for non-human primates

Abstract

Stable large-scale optogenetic interfaces for non-human primates (NHPs) have a great potential to answer fundamental questions about brain function and to develop novel therapies for neurological disorders. We have previously reported an interface that enables manipulation and recording from up to 2 cm² of cortical tissue by combining three technologies: 1- convection enhanced viral delivery to achieve high levels of expression across large cortical areas, 2- semi-transparent micro-electrocorticographic arrays to record from these expressing areas, and 3- artificial dura to protect the brain and provide optical access. Although this interface provided a unique platform to study network activity and brain connectivity, it was based on day-to-day implantation and explantation of the recording array which led to accelerated tissue growth on top of the brain and limited the efficient time window for optical access to only several weeks. We then needed to wait for a month or two to remove the tissue from the surface of the brain and regain optical access. Here, we are optimizing this interface by incorporating the recording array into the artificial dura to reduce the manipulation at the brain surface and increase the efficient optical access window to 3-9 months. We are using a transparent, flexible polymer as an insulator for our recording sites that can be easily molded into the artificial dura. Furthermore, we have optimized our stimulation setup to increase the number of simultaneous light stimulation locations. We believe this optimized interface has a great potential for long-term optogenetic experiments in non-human primates.