Background Advances in optogenetics have led to first reports of expression of light-gated ion-channels in non-human primates (NHPs). However, a major obstacle preventing effective application of optogenetics in NHPs and translation to optogenetic therapeutics is the absence of compatible multifunction optoelectronic probes for (1) precision light delivery, (2) low-interference electrophysiology, (3) protein fluorescence detection, and (4) repeated insertion with minimal brain trauma. New Method Here we describe a novel brain probe device, a “coaxial optrode”, designed to minimize brain tissue damage while microfabricated to perform simultaneous electrophysiology, light delivery and fluorescence measurements in the NHP brain. The device consists of a tapered, gold-coated optical fiber inserted in a polyamide tube. A portion of the gold coating is exposed at the fiber tip to allow electrophysiological recordings in addition to light delivery/collection at the tip. Results Coaxial optrode performance was demonstrated by experiments in rodents and NHPs, and characterized by computational models. The device mapped opsin expression in the brain and achieved precisely targeted optical stimulation and electrophysiology with minimal cortical damage. Comparison with Existing Methods Overall, combined electrical, optical and mechanical features of the coaxial optrode allowed a performance for NHP studies which was not possible with previously existing devices. Conclusions Coaxial optrode is currently being used in two NHP laboratories as a major tool to study brain function by inducing light modulated neural activity and behavior. By virtue of its design, the coaxial optrode can be extended for use as a chronic implant and multisite neural stimulation/recording.

Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest.