$7.75M for mapping circuits in the brain A new NSF Tech Hub will put tools to rapidly advance our understanding of the brain into the hands of neuroscientists.

The technology exists to stimulate and map circuits in the brain, but neuroscientists have yet to tap this potential.

Now, developers of these technologies are coming together to demonstrate and share them to drive a rapid advance in our understanding of the brain, funded by $7.75 million from the National Science Foundation.

“We want to put our technology into the hands of people who can really use it,” said Euisik Yoon, leader of the project and professor of electrical engineering and computer science at the University of Michigan.

By observing how mice and rats behave when certain neural circuits are stimulated, neuroscientists can better understand the function of those circuits in the brain. Then, after the rodents are euthanized, they can observe the neurons that had been activated and how they are connected. This connects the behavior that they had observed while the rodent was performing a controlled experiment with a detailed map of the relevant brain structure.

We can achieve structural and functional mapping at an unprecedented scale. Euisik Yoon, BME and EECS professor

It could lead to better understanding of disease in the brain as well as more effective treatments. In the nearer term, the details of neural circuitry could also help advance computing technologies that try to mimic the efficiency of the brain.

Over the last decade or so, three tools have emerged that, together, can enable the mapping of circuits within the brain. The most recent, from U-M, is an implant that uses light to stimulate specific neurons in genetically modified mice or rats and then records the response from other neurons with electrodes.

Probes like this one, which stimulate neurons with light and then record activity with electrodes, are just one facet of the technology suite that can help neuroscientists map circuits in the brain. Photo: Fan Wu, Yoon Lab, University of Michigan

Unlike earlier methods to stimulate the brain with light, with relatively large light-emitters that activated many nearby neurons, the new probes can target fewer neurons using microscopic LEDs that are about the same size as the brain cells themselves. This control makes the individual circuits easier to pick out.

The “pyramidal” neurons that cause action—rather than inhibit it—will be genetically modified so that they respond to the light.

“They are just one of the neuron types we are seeking to map,” said John Seymour, one of the co-investigators and U-M assistant research scientist in electrical engineering and computer science. “If you can record from motor cortex pyramidal neurons, you can predict arm movement, for example.”

To visualize the structure of pyramidal cells and other kinds of neurons, researchers need a way to see each tree in the brain’s forest. For this, co-investigator Dawen Cai, U-M assistant professor of cell and developmental biology, has been advancing a promising approach known as Brainbow. Genetically modified brain cells produce fluorescent tags, revealing each cell as a random color.

When it is time to examine the brain, a technique to make the brain transparent will remove all the fatty molecules from a brain and replace them with a clear gel, making it possible to see individual neurons. It was pioneered by another co-investigator, Viviana Gradinaru, who is a professor of biology and biological engineering at the California Institute of Technology.

“Not only may we understand how the signal is processed inside the brain, we can also find out how each neuron is connected together so that we achieve structural and functional mapping at an unprecedented scale,” Yoon said.

While these are the central tools, others at Michigan are working on methods to make the electrodes that record neuron activity even smaller and therefore more precise. In addition, a carbon wire electrode design could even pick up the chemical activity nearby, adding measurements of neurotransmitters as a new dimension of information.

To share these new tools, the team will bring in neuroscientists for annual workshops and then provide them with the hardware and software they need to run experiments in their own labs. For the tools that prove to be most useful, they will seek commercialization opportunities so that they remain available after the project ends.

The project is called Multimodal Integrated Neural Technologies (MINT) and has been awarded as a 5-year National Science Foundation NeuroNex Technology Hub.

Other co-investigators include Cynthia Chestek, U-M assistant professor of biomedical engineering; James Weiland, U-M professor of biomedical engineering; Ken Wise, the William Gould Dow Distinguished University Professor Emeritus of Electrical Engineering and Computer Science at U-M; and György Buzsáki, professor of neuroscience at New York University. Seymour and Yoon are also affiliated with biomedical engineering at U-M. Cai is affiliated with Michigan Medicine.

The neural probes with micro LEDs are made in the Lurie Nanofabrication Facility at U-M.

Original Publicationhttps://news.engin.umich.edu/2017/08/7-75m-for-mapping-circuits-in-the-brain/

Written By: Kate McAlpine, Senior Writer & Assistant News Editor, Michigan Engineering Communications and Marketing

Cover Caption: To follow the long, winding connections among neurons, a technique called “Brainbow” labels each neuron a random color. Credit: Dawen Cai, Cai Lab, University of Michigan

Video Caption: John Seymour explains how the new grant will help neurotechnologists further research to enable a better understanding of the pathways in the brain.

Tim Bruns wins NSF CAREER Award

U-M BME assistant professor Tim Bruns has received a prestigious National Science Foundation Faculty Early Career Development (CAREER) Award. Bruns leads the Peripheral Neural Engineering and Urodynamics Lab (pNEURO Lab) in Biomedical Engineering. The group is interested in developing interfaces with the peripheral nervous system to restore function and to examine systems-level neurophysiology, primarily focusing on organ function.  Bruns will use his award to study and model the behavior of neurons within dorsal root ganglia (DRG), unique structures next to the spinal cord that contain converging sensory nerves. This work will inform research and development of novel microelectrodes designed to record and stimulate DRG. Research in this area could lead to the restoration of nerve function for a wide range of disorders.

2016 NSF Fellowships

Three BME students won prestigious National Science Foundation (NSF) Graduate Research Fellowships in 2016. They include PhD students Chrono Nu from Cindy Chestek’s Cortical Neural Prosthetics Lab and Peter Washabaugh from Chandramouli Krishnan’s Neuromuscular and Rehabilitation Robotics Laboratory, as well as master’s student Makeda Stephenson from Scott Hollister’s Scaffold Tissue Engineering Group.


Nu, who has also been awarded a Department of Defense (DoD) National Defense Science and Engineering Graduate (NDSEG) Fellowship, is using data from cortical recording systems to conduct computational analyses of brain activity in primates, such as decoding motor-related neurological signals. Washabaugh is working to design robotic devices for use in physical therapy and to explore the neuromuscular changes associated with these therapies. Stephenson is developing functional architectures for tissue engineering scaffolds.

A ‘Communication Breakdown’ During General Anesthesia

May 09, 2016 2:39 PM

When ketamine is used for general anesthesia, two connected parts of the cortex turn to “isolated cognitive islands.”

It’s a topic that has long captivated doctors, scientists and the public — what exactly happens in your brain when you’re oblivious on the operating table?

Some anesthesia drugs work in a straightforward manner by dampening down neurons in the brain. The mechanism of one anesthetic, however, has proved elusive: ketamine.

Certain doses of ketamine induce general anesthesia, though brain activity can still be robust, says Cynthia Chestek, Ph.D., co-senior author of a new study in NeuroImage.

Ketamine is used often in patient care and in laboratory settings. The new paper examines the neurological mechanisms at work during ketamine anesthesia.

Co-senior authors Chestek and anesthesiologist George Mashour, M.D., Ph.D., led the research team, which took precise measurements down to the level of neurons in animal models.

“We found that general anesthesia reflects a communication breakdown in the cortex, even though sensory information is getting processed,” Mashour says. “But the processing appears to occur in isolated cognitive islands.”

Turns out, two adjacent parts of the brain that work together in the waking state simply stop talking to each other under general anesthesia. When awake, communication between the primary somatosensory cortex and the primary motor cortex is critical to normal function.

“This supports the idea that what anesthesia does to cause unconsciousness is interrupt communication between brain areas, stopping the processing of higher-level information,” says first author Karen Schroeder, a doctoral candidate in the U-M Department of Biomedical Engineering. “This was the first time anyone directly observed the interruption between the two areas using individual neurons.”

Different fields collaborating

Chestek’s biomedical engineering lab focuses on brain machine interfaces, recording activity of neurons and reading motor commands and sensory information in real time.

“This turned out to be really useful for the researchers in anesthesiology,” Chestek says. So her team got on board to measure both areas of the brain, which kept firing during anesthesia.

“As soon as we injected ketamine, the sensory information disappeared from the motor cortex. Normally these areas are tightly connected.”

The group plans to continue this work, turning next to investigate the level of anesthesia at which these changes in communication start to occur. They’re also looking into what the groups of neurons are doing under anesthesia when they are still active but no longer communicating with each other.

“These insights could potentially improve our ability to monitor patients’ level of consciousness,” Schroeder says.

Funding for the work came from the National Institutes of Health.