“Brain In Chip” Shows Neural Activity in 3-D

July 11, 2014
Kevin Hattori

Technion-Israel Institute of Technology researchers have developed a novel brain-like platform containing three dimensional cell networks that simulate complex aspects of brain activity, and which can be directly visualized. The breakthrough could provide a better way for understanding the structure and function of the brain and central nervous system. It might also prompt further developments in the field of neural interfaces, and applications for 3-D engineered networks ranging from basic brain research to a greater understanding of the impact of neurological drugs on nerve cell activity.

Microscopic image of brain nerve cells grown in an optonet culture, and the processes that form complex neural connectivity between them.

The findings by the team led by Prof. Shy Shoham, of the Department of Biomedical Engineering, were published recently in Nature Communications.

Until now, neuroscientists and medical researchers seeking a simple model for probing neural activity would most often use cell cultures grown on laboratory plates (two-dimensional neural cultures), but because  have provided a convenient model for many studies in the fields of neuroscience and medicine. But because these simple two-dimensional cultures contain only a single layer of cells, they do not exhibit the complex three-dimensional network connectivity found in real brains.  Previous attempts to develop 3-D models for studying the central nervous system have met with limited success, mostly because of the high complexity of developing a 3-D culture capable of simulating real brain tissue, and the challenges associated with developing methods for observing network activity in three dimensions.

The researchers overcame these challenges by growing their advanced culture in a clear gel that supports cellular growthand allows the cells to bind and form neural networks. “By optimizing the culturing conditions we achieved cellular density and composition similar to those found in the human brain, and were able to demonstrate the formation of connections between cells and of networks that maintain neural activity,” says team member Dr. Anat Marom.

To enable the study of network activity in 3-D, the researchers introduced organic or genetic dyes into the nerve cells so that it was possible to view ongoing network activity through a fluorescence microscope, earning them the nickname “Optonets.”

Viewing the cell activity in 3-D was the next challenge. To tackle this challenge, the researchers developed an advanced imaging system that utilizes a non-linear optical technique called “temporal focusing.” This advance in microscopy significantly improves their ability to view the activities of multiple brain cells in space and time and could allow for new insights about brain activity. Shoham and his study co-lead author Dr. Hod Dana say they now have the unprecedented ability to view more than a thousand cells within developing neural networks, exhibiting complex spontaneous activity patterns.

Also contributing to this research were Shir Paluch, Roman Dvorkin and Dr. Inbar Brosh.

The Technion-Israel Institute of Technology is a major source of the innovation and brainpower that drives the Israeli economy, and a key to Israel’s renown as the world’s “Start-Up Nation.” Its three Nobel Prize winners exemplify academic excellence. Technion people, ideas and inventions make immeasurable contributions to the world including life-saving medicine, sustainable energy, computer science, water conservation and nanotechnology. The Joan and Irwin Jacobs Technion-Cornell Institute is a vital component of Cornell NYC Tech, and a model for graduate applied science education that is expected to transform New York City’s economy.

American Technion Society (ATS) donors provide critical support for the Technion—more than $1.95 billion since its inception in 1940. Based in New York City, the ATS and its network of chapters across the U.S. provide funds for scholarships, fellowships, faculty recruitment and chairs, research, buildings, laboratories, classrooms and dormitories, and more.