Probe ‘takes notes’ as light excites neurons

Zinc oxide is both optically transparent and able to conduct electricity. The material made it possible to make a device (enlarged image above) that could both stimulate brain activity with light and record activity in multiple neural microcircuits at the same time. (Credit: Nurmikko Lab/Brown)

The developing field of optogenetics makes it possible for scientists to control brain activity using pulses of light.

Now, researchers have developed an optoelectronic device that opens up the possibility of stimulating neural microcircuits in the brain while also monitoring changes in neural activity.

“We think this is a window-opener,” says Joonhee Lee, one of the lead authors of a new paper in Nature Methods and a senior research associate in the lab of Arto Nurmikko, professor of engineering at Brown University.

How does optogenetics work?

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. In principle, the method gives researchers unprecedented ability to control specific brain cells at specific times.

Until now, simultaneous optogenetic stimulation and recording of brain activity rapidly across multiple points within a brain microcircuit of interest has proven difficult. Doing 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 and not ideal for insertion into a brain—and because the emitters and the sensors were necessarily a hundreds of micrometers apart, a sizable distance, the link between stimulation and recorded signal was ambiguous.

Neuron circuits, not single neurons

The new compact, integrated device developed by Nurmikko’s lab begins with the unique advantages endowed by a so-called wide-bandgap semiconductor called zinc oxide. It is optically transparent yet able readily to conduct an electrical current.

“Very few materials have that pair of physical properties,” Lee says. “The combination makes it possible to both stimulate and detect with the same material.”

Lee and colleagues developed a novel microfabrication method with Nurmikko to shape the material into a monolithic chip just a few millimeters square with sixteen micrometer sized pin-like “optoelectrodes,” each capable of both delivering light pulses and sensing electrical current. The array of optoelectrodes enables the device to couple to neural microcircuits composed of many neurons rather than single neurons.

Such ability to stimulate and record at the network level on the spatial and time scales at which they operate is key, Nurmikko says. Neural circuits, not single neurons, drive brain functions.

“For example, when I move my hand, that’s an example of action driven by specific network-level activity in the brain,” he says. “Our new device approach gives scientists and engineers a tool in applying the full power of optogenetics as a means of neural stimulation, while providing the means to read activity of perturbed networks at multiple points at high spatial precision and time resolution.”

Testing the invention

Ilker Ozden, assistant research professor, led the initial testing of the device in rodent models. The researchers looked at the extent to which different light intensities could stimulate network activity. The tests showed that increasing optical power led to distinct recruitment of neuronal circuits revealing functional connectivity in the targeted network.

“We went over a range of optical power that was large—over three orders of magnitude—and in so doing we got a range of network-related responses. In particular, we could replicate an activity pattern naturally occurring in the brain,” Ozden says. “It gave us a new insight into how optogenetics operates on the network level.”

Nurmikko’s group, together with the collaborator Yoon-Kyu Song’s lab in Seoul, plans to continue development of the device. Their next steps anticipate the use of the new device technology as chronic implant in non-human primates at potentially hundreds of points and, depending on progress in worldwide research on optogenetics, perhaps one day even in humans.

“At least, the initial building blocks are here,” says Nurmikko.

The Defense Advanced Research Projects Agency’s REPAIR program and the National Science Foundation supported the work.

Source: Brown University