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Optogenetics allows for optical manipulation of neuronal activity and has been increasingly combined with intra- and extra-cellular electrophysiological recordings. Genetically-identified classes of neurons are optically manipulated, though the versatility of optogenetics would be increased if independent control of distinct neural populations could be achieved on a sufficient spatial and temporal resolution. We report a scalable multi-site optoelectrode design that allows simultaneous optogenetic control of two spatially intermingled neuronal populations in vivo . We describe the design, fabrication, and assembly of low-noise, multi-site/multi-color optoelectrodes. Each shank of the four-shank assembly is monolithically integrated with 8 recording sites and a dual-color waveguide mixer with a 7 × 30 μm cross-section, coupled to 405 nm and 635 nm injection laser diodes (ILDs) via gradient-index (GRIN) lenses to meet optical and thermal design requirements. To better understand noise on the recording channels generated during diode-based activation, we developed a lumped-circuit modeling approach for EMI coupling mechanisms and used it to limit artifacts to amplitudes under 100 μV upto an optical output power of 450 μW. We implanted the packaged devices into the CA1 pyramidal layer of awake mice, expressing Channelrhodopsin-2 in pyramidal cells and ChrimsonR in paravalbumin-expressing interneurons, and achieved optical excitation of each cell type using sub-mW illumination. We highlight the potential use of this technology for functional dissection of neural circuits.

Dual color optogenetic control of neural populations using low-noise, multishank optoelectrodes