Tag Archives: neurobiology

Will you be my friend? Yes, after we activate our ultraminiature, wireless, battery-free, fully implantable devices

Perhaps I’m the only one who’s disconcerted?

Here’s the research (in text form) as to why we’re watching these scampering, momentary mouse friends, from a May 10, 2021 Northwestern University news release (also on EurekAlert) by Amanda Morris,

Northwestern University researchers are building social bonds with beams of light.

For the first time ever, Northwestern engineers and neurobiologists have wirelessly programmed — and then deprogrammed — mice to socially interact with one another in real time. The advancement is thanks to a first-of-its-kind ultraminiature, wireless, battery-free and fully implantable device that uses light to activate neurons.

This study is the first optogenetics (a method for controlling neurons with light) paper exploring social interactions within groups of animals, which was previously impossible with current technologies.

The research was published May 10 [2021] in the journal Nature Neuroscience.

The thin, flexible, wireless nature of the implant allows the mice to look normal and behave normally in realistic environments, enabling researchers to observe them under natural conditions. Previous research using optogenetics required fiberoptic wires, which restrained mouse movements and caused them to become entangled during social interactions or in complex environments.

“With previous technologies, we were unable to observe multiple animals socially interacting in complex environments because they were tethered,” said Northwestern neurobiologist Yevgenia Kozorovitskiy, who designed the experiment. “The fibers would break or the animals would become entangled. In order to ask more complex questions about animal behavior in realistic environments, we needed this innovative wireless technology. It’s tremendous to get away from the tethers.”

“This paper represents the first time we’ve been able to achieve wireless, battery-free implants for optogenetics with full, independent digital control over multiple devices simultaneously in a given environment,” said Northwestern bioelectronics pioneer John A. Rogers, who led the technology development. “Brain activity in an isolated animal is interesting, but going beyond research on individuals to studies of complex, socially interacting groups is one of the most important and exciting frontiers in neuroscience. We now have the technology to investigate how bonds form and break between individuals in these groups and to examine how social hierarchies arise from these interactions.”

Kozorovitskiy is the Soretta and Henry Shapiro Research Professor of Molecular Biology and associate professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences. She also is a member of the Chemistry of Life Processes Institute. Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine and the director of the Querrey Simpson Institute for Bioelectronics.

Kozorovitskiy and Rogers led the work with Yonggang Huang, the Jan and Marcia Achenbach Professor in Mechanical Engineering at McCormick, and Zhaoqian Xie, a professor of engineering mechanics at Dalian University of Technology in China. The paper’s co-first authors are Yiyuan Yang, Mingzheng Wu and Abraham Vázquez-Guardado — all at Northwestern.

Promise and problems of optogenetics

Because the human brain is a system of nearly 100 billion intertwined neurons, it’s extremely difficult to probe single — or even groups of — neurons. Introduced in animal models around 2005, optogenetics offers control of specific, genetically targeted neurons in order to probe them in unprecedented detail to study their connectivity or neurotransmitter release. Researchers first modify neurons in living mice to express a modified gene from light-sensitive algae. Then they can use external light to specifically control and monitor brain activity. Because of the genetic engineering involved, the method is not yet approved in humans.

“It sounds like sci-fi, but it’s an incredibly useful technique,” Kozorovitskiy said. “Optogenetics could someday soon be used to fix blindness or reverse paralysis.”

Previous optogenetics studies, however, were limited by the available technology to deliver light. Although researchers could easily probe one animal in isolation, it was challenging to simultaneously control neural activity in flexible patterns within groups of animals interacting socially. Fiberoptic wires typically emerged from an animal’s head, connecting to an external light source. Then a software program could be used to turn the light off and on, while monitoring the animal’s behavior.

“As they move around, the fibers tugged in different ways,” Rogers said. “As expected, these effects changed the animal’s patterns of motion. One, therefore, has to wonder: What behavior are you actually studying? Are you studying natural behaviors or behaviors associated with a physical constraint?”

Wireless control in real time

A world-renowned leader in wireless, wearable technology, Rogers and his team developed a tiny, wireless device that gently rests on the skull’s outer surface but beneath the skin and fur of a small animal. The half-millimeter-thick device connects to a fine, flexible filamentary probe with LEDs on the tip, which extend down into the brain through a tiny cranial defect.

The miniature device leverages near-field communication protocols, the same technology used in smartphones for electronic payments. Researchers wirelessly operate the light in real time with a user interface on a computer. An antenna surrounding the animals’ enclosure delivers power to the wireless device, thereby eliminating the need for a bulky, heavy battery.

Activating social connections

To establish proof of principle for Rogers’ technology, Kozorovitskiy and colleagues designed an experiment to explore an optogenetics approach to remote-control social interactions among pairs or groups of mice.

When mice were physically near one another in an enclosed environment, Kozorovitskiy’s team wirelessly synchronously activated a set of neurons in a brain region related to higher order executive function, causing them to increase the frequency and duration of social interactions. Desynchronizing the stimulation promptly decreased social interactions in the same pair of mice. In a group setting, researchers could bias an arbitrarily chosen pair to interact more than others.

“We didn’t actually think this would work,” Kozorovitskiy said. “To our knowledge, this is the first direct evaluation of a major long-standing hypothesis about neural synchrony in social behavior.”

Here’s a citation and a link to the paper,

Wireless multilateral devices for optogenetic studies of individual and social behaviors by Yiyuan Yang, Mingzheng Wu, Amy J. Wegener, Jose G. Grajales-Reyes, Yujun Deng, Taoyi Wang, Raudel Avila, Justin A. Moreno, Samuel Minkowicz, Vasin Dumrongprechachan, Jungyup Lee, Shuangyang Zhang, Alex A. Legaria, Yuhang Ma, Sunita Mehta, Daniel Franklin, Layne Hartman, Wubin Bai, Mengdi Han, Hangbo Zhao, Wei Lu, Yongjoon Yu, Xing Sheng, Anthony Banks, Xinge Yu, Zoe R. Donaldson, Robert W. Gereau IV, Cameron H. Good, Zhaoqian Xie, Yonggang Huang, Yevgenia Kozorovitskiy and John A. Rogers. Nature Neuroscience (2021)
DOI: https://doi.org/10.1038/s41593-021-00849-x Published 10 May 2021

This paper is behind a paywall.

This latest research seems to be the continuation of research featured here in a July 16, 2019 posting: “Controlling neurons with light: no batteries or wires needed.”

Resistive memory from University of California Riverside (replacing flash memory in mobile devices) and Boise State University (neuron chips)

Today, (Aug. 19, 2 013)I have two items on memristors. First, Dexter Johnson provides some context for understanding why a University of California Riverside research team’s approach to creating memristors is exciting some interest in his Aug. 17, 2013 posting (Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] website), Note: Links have been removed,

The heralding of the memristor, or resistive memory, and the long-anticipated demise of flash memory have both been tracking on opposite trajectories with resistive memory expected to displace flash ever since the memristor was first discovered by Stanley Williams’ group at Hewlett Packard in 2008.

The memristor has been on a rapid development track ever since and has been promised to be commercially available as early as 2014, enabling 10 times greater embedded memory for mobile devices than currently available.

The obsolescence of flash memory at the hands of the latest nanotechnology has been predicted for longer than the commercial introduction of the memristor. But just at the moment it appears it’s going to reach its limits in storage capacity along comes a new way to push its capabilities to new heights, sometimes thanks to a nanomaterial like graphene.

In addition to the graphene promise, Dexter goes on to discuss another development,  which could push memory capabilities and which is mentioned in an Aug. 14, 2013 news item on ScienceDaily (and elsewhere),

A team at the University of California, Riverside Bourns College of Engineering has developed a novel way to build what many see as the next generation memory storage devices for portable electronic devices including smart phones, tablets, laptops and digital cameras.

The device is based on the principles of resistive memory [memristor], which can be used to create memory cells that are smaller, operate at a higher speed and offer more storage capacity than flash memory cells, the current industry standard. Terabytes, not gigbytes, will be the norm with resistive memory.

The key advancement in the UC Riverside research is the creation of a zinc oxide nano-island on silicon. It eliminates the need for a second element called a selector device, which is often a diode.

The Aug. 13, 2013 University of California Riverside news release by Sean Nealon, which originated the news item, further describes the limitations of flash memory and reinforces the importance of being able to eliminate a component (selector device),

Flash memory has been the standard in the electronics industry for decades. But, as flash continues to get smaller and users want higher storage capacity, it appears to reaching the end of its lifespan, Liu [Jianlin Liu, a professor of electrical engineering] said.

With that in mind, resistive memory is receiving significant attention from academia and the electronics industry because it has a simple structure, high-density integration, fast operation and long endurance.

Researchers have also found that resistive memory can be scaled down in the sub 10-nanometer scale. (A nanometer is one-billionth of a meter.) Current flash memory devices are roughly using a feature size twice as large.

Resistive memory usually has a metal-oxide-metal structure in connection with a selector device. The UC Riverside team has demonstrated a novel alternative way by forming self-assembled zinc oxide nano-islands on silicon. Using a conductive atomic force microscope, the researchers observed three operation modes from the same device structure, essentially eliminating the need for a separate selector device.

Here’s a link to and a citation for the researchers’ published paper,

Multimode Resistive Switching in Single ZnO Nanoisland System by Jing Qi, Mario Olmedo, Jian-Guo Zheng, & Jianlin Liu. Scientific Reports 3, Article number: 2405 doi:10.1038/srep02405 Published 12 August 2013

This study is open access.

Meanwhile, Boise State University (Idaho, US) is celebrating a new project, CIF: Small: Realizing Chip-scale Bio-inspired Spiking Neural Networks with Monolithically Integrated Nano-scale Memristors, which was announced in an Aug. 17, 2013 news item on Azonano,

Electrical and computer engineering faculty Elisa Barney Smith, Kris Campbell and Vishal Saxena are joining forces on a project titled “CIF: Small: Realizing Chip-scale Bio-inspired Spiking Neural Networks with Monolithically Integrated Nano-scale Memristors.”

Team members are experts in machine learning (artificial intelligence), integrated circuit design and memristor devices. Funded by a three-year, $500,000 National Science Foundation grant, they have taken on the challenge of developing a new kind of computing architecture that works more like a brain than a traditional digital computer.

“By mimicking the brain’s billions of interconnections and pattern recognition capabilities, we may ultimately introduce a new paradigm in speed and power, and potentially enable systems that include the ability to learn, adapt and respond to their environment,” said Barney Smith, who is the principal investigator on the grant.

The Aug. 14, 2013 Boise State University news release by Kathleen Tuck, which originated the news item, describes the team’s focus on mimicking the brain’s capabilities ,

One of the first memristors was built in Campbell’s Boise State lab, which has the distinction of being one of only five or six labs worldwide that are up to the task.

The team’s research builds on recent work from scientists who have derived mathematical algorithms to explain the electrical interaction between brain synapses and neurons.

“By employing these models in combination with a new device technology that exhibits similar electrical response to the neural synapses, we will design entirely new computing chips that mimic how the brain processes information,” said Barney Smith.

Even better, these new chips will consume power at an order of magnitude lower than current computing processors, despite the fact that they match existing chips in physical dimensions. This will open the door for ultra low-power electronics intended for applications with scarce energy resources, such as in space, environmental sensors or biomedical implants.

Once the team has successfully built an artificial neural network, they will look to engage neurobiologists in parallel to what they are doing now. A proposal for that could be written in the coming year.

Barney Smith said they hope to send the first of the new neuron chips out for fabrication within weeks.

With the possibility that HP Labs will make its ‘memristor chips‘ commercially available in 2014 and neuron chips fabricated for the Boise State University researchers within weeks of this Aug. 19, 2013 date, it seems that memristors have been developed at a lightning fast pace. It’s been a fascinating process to observe.