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

Komal Kampasi,Eran Stark,Sam McKenzie,György Buzsáki,John Seymour,Mihály Vöröslakos,Kensall D. Wise,Euisik Yoon,Daniel F. English

doi:10.1038/s41378-018-0009-2

Abstract

Optogenetics allows for optical manipulation of neuronal activity and has been increasingly combined with intracellular and extracellular 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 multisite 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, multisite/multicolor 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.

Highlights

Optical perturbation of genetically-defined neuron types[1,2] combined with large-scale recordings[3,4,5] has become a widespread tool for neural circuit analysis
A multi-shank design involves the alignment of eight injection laser diodes (ILDs)-GRINwaveguide pairs in all three axes, making it critical to keep designed losses to a minimum
Since 405 nm suffers more scattering losses than 635 nm, ILDs were arranged in such manner such that 405 nm ILDs were coupled with mixer arms with the lowest loss and 635 nm ILDs were coupled with mixer arms with the highest loss

Summary

Introduction

Optical perturbation of genetically-defined neuron types[1,2] combined with large-scale recordings[3,4,5] has become a widespread tool for neural circuit analysis. Optoelectrode designs were either bulky and lacked spatial precision for neural optical stimulation[21,22,23] and/or incorporated the use of fibers[4] which limits scaling. An optical mixer enables multicolor illumination at a common port (7 × 30 μm) (Supplementary Movie S1), which was used to activate two spatially intermingled cell types in hippocampal CA1 region of awake behaving mice: pyramidal cells (PYR) expressing the blue-light sensitive Channelrhodopsin-2, and parvalbumin-expressing (PV) cells expressing the redlight sensitive opsin ChrimsonR. Our results demonstrate that these novel optoelectrodes can be used for neural circuit interrogation that requires the parametric control of two types of neurons in awake mammals

Methods

Results

Conclusion