A coaxial optrode as multifunction write-read probe for optogenetic studies in non-human primates.

ABSTRACT

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.