Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe

Lizhu Li,Xue Cai,Xin Fu,Changbo Liu,Yu Zhao,Huachun Wang,He Ding,Guo Tang,Xing Sheng,Lihui Lu,Zhao Shi,Minmin Luo,Yuqi Ren,Yang Xie,Dali Cheng,Lan Yin

doi:10.1038/s41467-022-28539-7

Abstract

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable. Here we report bidirectional neuronal activity manipulation accomplished by a wireless, dual-color optogenetic probe in synergy with the co-expression of two spectrally distinct opsins (ChrimsonR and stGtACR2) in a rodent model. The flexible probe comprises vertically assembled, thin-film microscale light-emitting diodes with a lateral dimension of 125 × 180 µm2, showing colocalized red and blue emissions and enabling chronic in vivo operations with desirable biocompatibilities. Red or blue irradiations deterministically evoke or silence neurons co-expressing the two opsins. The probe interferes with dopaminergic neurons in the ventral tegmental area of mice, increasing or decreasing dopamine levels. Such bidirectional regulations further generate rewarding and aversive behaviors and interrogate social interactions among multiple mice. These technologies create numerous opportunities and implications for brain research.

Highlights

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable
Apart from various waveguide-based emitters interfacing with external light sources[20–22], recently developed implantable probes based on thin-film, microscale optoelectronic devices have offered a viable solution to versatile neural modulations in untethered animals, when incorporated with various wirelessly operating systems based on radio frequency (RF) antennas[23–25], near-field communication (NFC)[26], Bluetooth chips[27], and infrared receivers[28]
The probe structure comprises of a copper (Cu)-coated polyimide (PI) thinfilm substrate, an indium gallium phosphide (InGaP) red LED, a silicon oxide (SiO2)/titanium oxide (TiO2)-based dielectric filter, and an indium gallium nitride (InGaN) blue LED

Summary

Introduction

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable. Apart from various waveguide-based emitters interfacing with external light sources[20–22], recently developed implantable probes based on thin-film, microscale optoelectronic devices have offered a viable solution to versatile neural modulations in untethered animals, when incorporated with various wirelessly operating systems based on radio frequency (RF) antennas[23–25], near-field communication (NFC)[26], Bluetooth chips[27], and infrared receivers[28]. In addition to these achievements, bidirectional neural modulations, by activating or suppressing the same or different populations of cells in behaving animals with the light of different wavelengths, are highly demanded. In vivo behavioral results associated with the red and blue stimulations in the VTA are validated by increased or decreased dopamine levels detected in the nucleus accumbens (NAc) in real time

Methods

Results

Conclusion