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.
Although several studies have shown the feasibility of using optogenetics in non-human primates (NHP), reliable largescale chronic interfaces have not yet been reported for such studies in NHP. Here we introduce a chronic setup that permits repeated, daily optogenetic stimulation and large-scale recording from the same sites in NHP cortex. The setup combines optogenetics with a transparent artificial dura (AD) and high-density micro-electrocorticography (μECoG). To obtain expression across large areas of cortex, we infused AAV5-CamKIIa-C1V1-EYFP viral vector using an infusion technique based on convection-enhanced delivery (CED) in primary somatosensory (S1) and motor (M1) cortices. By epifluorescent imaging through AD we were able to confirm high levels of expression covering about 110 mm2 of S1 and M1. We then incorporated a 192-channel μECoG array spanning 192 mm2 into the AD for simultaneous electrophysiological recording during optical stimulation. The array consists of patterned Pt-Au-Pt metal traces embedded in ~10 μm Parylene-C insulator. The parylene is sufficiently transparent to allow minimally attenuated optical access for optogenetic stimulation. The array was chronically implanted over the opsin-expressing areas in M1 and S1 for over two weeks. Optical stimulation was delivered via a fiber optic placed on the surface of the AD. With this setup, we recorded reliable evoked activity following light stimulation at several locations. Similar responses were recorded across tens of days, however a decline in the light-evoked signal amplitude was observed during this period due to the growth of dural tissue over the array. These results show the feasibility of a chronic interface for combined largescale optogenetic stimulation and cortical recordings across days.