Brown University School of Engineering and Seoul National University researchers have combined optoelectronics and intracortical neural recording for the first time — enabling neuroscientists to optically stimulate neuron activity while simultaneously recording the effects of the stimulation on associated neural microcircuits.

Described in the journal Nature Methods, the new compact, integrated device uses a semiconductor called zinc oxide, which is optically transparent yet able to conduct an electrical current. That makes it possible to both stimulate and detect with the same material.

The chip is just a few millimeters square with sixteen micrometer-sized pin-like “optoelectrodes,” each capable of both delivering light pulses at micrometer scale and sensing electrical current. The array of optoelectrodes also enables the device to couple to neural microcircuits composed of many neurons rather than single neurons and with millisecond precision.

“We think this is a window-opener,” said Joonhee Lee, a senior research associate in Professor Arto Nurmikko’s lab and one of the lead authors of the new paper. “The ability to rapidly perturb neural circuits according to specific spatial patterns and at the same time reconstruct how the circuits involved are perturbed, is in our view a substantial advance.”

First introduced around 2005, optogenetics involves genetically engineering neurons to express light-sensitive proteins on their membranes. With those proteins expressed, pulses of light can be used to either promote or suppress activity in those particular cells. The method gives researchers, in principle, unprecedented ability to control specific brain cells at specific times.

But until now, simultaneous optogenetic stimulation and recording of brain activity rapidly across multiple points within a brain microcircuit of interest has proven difficult. It requires a device that can both generate a spatial pattern of light pulses and detect the dynamical patterns of electrical reverberations generated by excited cellular activity.

Previous attempts to do this involved devices that cobbled together separate components for light emission and electrical sensing. Such probes were physically bulky, which is not ideal for insertion into a brain. And because the emitters and the sensors were necessarily at hundreds of micrometers apart, a sizable distance, the link between stimulation and recorded signal was not reliable.

The researchers’ next steps are developing a wireless version and using the technology as a chronic implant in non-human primates at potentially hundreds of points and, depending on future progress in worldwide research on optogenetics, perhaps even one day in humans.

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Abstract of Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording

Optogenetics, the selective excitation or inhibition of neural circuits by light, has become a transformative approach for dissecting functional brain microcircuits, particularly in in vivorodent models, owing to the expanding libraries of opsins and promoters. Yet there is a lack of versatile devices that can deliver spatiotemporally patterned light while performing simultaneous sensing to map the dynamics of perturbed neural populations at the network level. We have created optoelectronic actuator and sensor microarrays that can be used as monolithic intracortical implants, fabricated from an optically transparent, electrically highly conducting semiconductor ZnO crystal. The devices can perform simultaneous light delivery and electrical readout in precise spatial registry across the microprobe array. We applied the device technology in transgenic mice to study light-perturbed cortical microcircuit dynamics and their effects on behavior. The functionality of this device can be further expanded to optical imaging and patterned electrical microstimulation.