Tag Archives: wireless remote activation of neurons

On the verge of controlling neurons by wireless?

Scientists have controlled a mouse’s neurons with a wireless device (and unleashed some paranoid fantasies? well, mine if no one else’s) according to a July 16, 2015 news item on Nanowerk (Note: A link has been removed),

A study showed that scientists can wirelessly determine the path a mouse walks with a press of a button. Researchers at the Washington University School of Medicine, St. Louis, and University of Illinois, Urbana-Champaign, created a remote controlled, next-generation tissue implant that allows neuroscientists to inject drugs and shine lights on neurons deep inside the brains of mice. The revolutionary device is described online in the journal Cell (“Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics”). Its development was partially funded by the [US] National Institutes of Health [NIH].

The researchers have made an image/illustration of the probe available,

Mind Bending Probe Scientists used soft materials to create a brain implant a tenth the width of a human hair that can wirelessly control neurons with lights and drugs. Courtesy of Jeong lab, University of Colorado Boulder.

A July 16, 2015 US NIH National Institute of Neurological Disorders and Stroke news release, which originated the news item, describes the study and notes that instructions for building the implant are included in the published study,

“It unplugs a world of possibilities for scientists to learn how brain circuits work in a more natural setting.” said Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology at Washington University School of Medicine and a senior author of the study.

The Bruchas lab studies circuits that control a variety of disorders including stress, depression, addiction, and pain. Typically, scientists who study these circuits have to choose between injecting drugs through bulky metal tubes and delivering lights through fiber optic cables. Both options require surgery that can damage parts of the brain and introduce experimental conditions that hinder animals’ natural movements.

To address these issues, Jae-Woong Jeong, Ph.D., a bioengineer formerly at the University of Illinois at Urbana-Champaign, worked with Jordan G. McCall, Ph.D., a graduate student in the Bruchas lab, to construct a remote controlled, optofluidic implant. The device is made out of soft materials that are a tenth the diameter of a human hair and can simultaneously deliver drugs and lights.

“We used powerful nano-manufacturing strategies to fabricate an implant that lets us penetrate deep inside the brain with minimal damage,” said John A. Rogers, Ph.D., professor of materials science and engineering, University of Illinois at Urbana-Champaign and a senior author. “Ultra-miniaturized devices like this have tremendous potential for science and medicine.”

With a thickness of 80 micrometers and a width of 500 micrometers, the optofluidic implant is thinner than the metal tubes, or cannulas, scientists typically use to inject drugs. When the scientists compared the implant with a typical cannula they found that the implant damaged and displaced much less brain tissue.

The scientists tested the device’s drug delivery potential by surgically placing it into the brains of mice. In some experiments, they showed that they could precisely map circuits by using the implant to inject viruses that label cells with genetic dyes. In other experiments, they made mice walk in circles by injecting a drug that mimics morphine into the ventral tegmental area (VTA), a region that controls motivation and addiction.

The researchers also tested the device’s combined light and drug delivery potential when they made mice that have light-sensitive VTA neurons stay on one side of a cage by commanding the implant to shine laser pulses on the cells. The mice lost the preference when the scientists directed the device to simultaneously inject a drug that blocks neuronal communication. In all of the experiments, the mice were about three feet away from the command antenna.

“This is the kind of revolutionary tool development that neuroscientists need to map out brain circuit activity,” said James Gnadt, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).  “It’s in line with the goals of the NIH’s BRAIN Initiative.”

The researchers fabricated the implant using semi-conductor computer chip manufacturing techniques. It has room for up to four drugs and has four microscale inorganic light-emitting diodes. They installed an expandable material at the bottom of the drug reservoirs to control delivery. When the temperature on an electric heater beneath the reservoir rose then the bottom rapidly expanded and pushed the drug out into the brain.

“We tried at least 30 different prototypes before one finally worked,” said Dr. McCall.

“This was truly an interdisciplinary effort,” said Dr. Jeong, who is now an assistant professor of electrical, computer, and energy engineering at University of Colorado Boulder. “We tried to engineer the implant to meet some of neurosciences greatest unmet needs.”

In the study, the scientists provide detailed instructions for manufacturing the implant.

“A tool is only good if it’s used,” said Dr. Bruchas. “We believe an open, crowdsourcing approach to neuroscience is a great way to understand normal and healthy brain circuitry.”

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

Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics by Jae-Woong Jeong, Jordan G. McCall, Gunchul Shin, Yihui Zhang, Ream Al-Hasani, Minku Kim, Shuo Li, Joo Yong Sim, Kyung-In Jang, Yan Shi, Daniel Y. Hong, Yuhao Liu, Gavin P. Schmitz, Li Xia, Zhubin He, Paul Gamble, Wilson Z. Ray, Yonggang Huang, Michael R. Bruchas, and John A. Rogers.  Cell, July 16, 2015. DOI: 10.1016/j.cell.2015.06.058

This paper is behind a paywall.

I last wrote about wireless activation of neurons in a May 28, 2014 posting which featured research at the University of Massachusetts Medical School.

Wireless nano for remotely activating neurons

Every once in a while, there’s a piece of research that disconcerts me and this would be one of those pieces. From a May 22, 2014 news item on Nanowerk,

Yang Xiang, PhD, assistant professor of neurobiology at University of Massachusetts Medical School, has received a three-year, $900,000 grant from the Human Frontiers Science Program to lead an international team of scientists, including Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology, in the development and implementation of a new optogenetic platform that can remotely activate neurons inside a free-moving organism.

Using a new class of nanoparticles developed by Dr. Han, Dr. Xiang and colleagues propose to selectively turn on non-image forming photoreceptors (NIFP) inside mice and Drosophila unencumbered by the fiber optic wires used in currently available optogenetic technologies. By wirelessly stimulating these photoreceptors, which are able to sense light even though they don’t generate vision, scientists can better understand their role in regulating physiological functions such as circadian rhythm, sleep and melatonin secretion. The hope is that this new technology can also be used to study the links between other types of neurons, physiology and behavior.

A May 22, 2014 University of Massachusetts Medical School news release by Jim Fessenden, which originated the news item, describes optogenetics and some of its challenges,

“Current optogenetic technologies are limited in their application because they require using ‘wired’ fiber optic implants to deliver blue light to activate neuron activities,” said Xiang. “This is a major technological problem that has become an obstacle to understanding the physiological role NIFP play in animal behavior. If we’re able to overcome this hurdle by using the nanoparticles developed by Dr. Han, it would open the door to more informed investigations of not only NIFP but a wide range of neurons and their effect on behavior.”

In use for only about a decade, optogenetic technology combines techniques from optics and genetics, allowing scientists to precisely control activities of individual neurons using light. By genetically inserting light-activated biological molecules such as channelrhodopsins, a family of proteins found in algae, into neurons, scientists can instantaneously turn them on using beams of blue light with millisecond precision.

A limiting factor to the wider application of this technology, however, is that blue wavelengths are unable to penetrate skin, bone and other tissues deep enough to activate the neurons inside free-moving animals. To overcome this obstacle, current techniques require the insertion of fiber optic wires close enough to the neurons so the light that activates them can be delivered. This technique restricts animal movement and makes it difficult to observe behavioral responses in natural conditions. This fiber optic approach further limits scientists’ ability to study behavior over longer periods of time as the effectiveness of light delivery is relatively short due to scarring.

The news release describes the new technique proposed by Xiang and his associates,

Han has developed an “upconversion nanoparticle” (UCNP) that has the potential to solve the limitations of wired optogenetic techniques. These nanoparticles are capable of absorbing infrared light that can’t be seen and converting it into visible blue light. In contrast to blue light, infrared light is capable of penetrating skin and tissue to a depth of several centimeters. Xiang and Han believe these nanoparticles, tuned to emit blue light, can be inserted into the brain and used as a substitute for traditional fiber optics to wirelessly activate neurons in animals.

The hope is that the nanoparticles will absorb infrared light that passes through the tissue, and convert it to blue light inside the animal. This blue light would then activate the NFIPs. If successful, Xiang and colleagues will be able to observe any changes in animal behavior brought about by activating these non-image forming photoreceptors.

“The nanoparticles act as a kind of relay station,” said Han. “They convert the low-energy red light into a high-energy blue light that can activate the neurons. This technique completely alleviates the need to use intrusive fiber optic wires. It vastly simplifies the technology and expands the potential uses for optogenetics.”

Xiang said, “In many ways, this is the perfect bridge between a technological advancement and an important biological question. With these nanoparticles it’s possible for us to begin answering fundamental neurobiological questions about NIFPs.

“More broadly, it would open up the possibility of using other model organisms, such as Drosophila, that can’t be used with the current wired optogenetic technologies, to investigate and answer important questions about how neural activities regulate behavior.”

Illogical as it is, the idea that neurons could be wirelessly and remotely activated by someone other the owner of those neurons disturbs me even though I know drugs are commonly used to do much the same thing in humans.

In any event, the news release provides this final paragraph about the funding,

HFSP [Human Frontiers Science Program] awards are given to highly innovative teams that demonstrate that they have developed and can test a paradigm-shifting idea that holds promise for the development of new approaches to problems in the life sciences with potential to advance the field of research significantly.

I looked up the HFSP online and found this on the About Us page on the HFSP website,

The Human Frontier Science Program is a program of funding for frontier research in the life sciences. It is implemented by the International Human Frontier Science Program Organization (HFSPO) with its office in Strasbourg.

The members of the HFSPO, the so-called Management Supporting Parties (MSPs) are the contributing countries and the European Union, which contributes on behalf of the non-G7 EU members.

The current MSPs are Australia, Canada, France, Germany, India, Italy, Japan, Republic of Korea, Norway, New Zealand, Switzerland the United Kingdom, the United States of America and the European Union. [emphasis mine]

I was not expecting to find Canada on that list.