NYSCF Innovator Pioneers Method For Imaging Electrical Activity In Neurons

Voltage is something scientists can measure with a multimeter, but it isn’t something we thought we could see with our eyes—until now.

NYSCF — Robertson Investigator Alumnus Ed Boyden, PhD, and his team at the MIT Media Lab have recently developed a new tool for imaging the electrical activity of neurons in the brain using a fluorescent protein that glows when the neuron is active.

Neurons talk to each other by sending electrical signals. Typically, we read electrical signals by placing an electrode in the brain and recording the activity of a single neuron. But Boyden explains that this only provides us with half of the story.

“It’s like trying to understand a phone conversation by hearing only one person talk,” – Dr. Ed Boyden

If we can see all the neurons that are electrically active in a circuit at one time, we can get a better idea of how our brains are organized, how the neurons are communicating with each other, and how these circuits give rise to different brain functions.

The researchers were interested in finding a protein that could successfully image multiple neurons, but identifying one that can do this accurately and consistently is usually a tedious task. To speed up the process, Dr. Boyden and his team created a robot that could quickly test millions of proteins and pick the best one.

The researchers first created a bunch of mutated versions of a certain light-sensitive protein, put them into cells, let the cells grow, and then use an automated microscope to take pictures of them. The robot analyzed the pictures to see which proteins fit the researchers’ ideal criteria, and ultimately identified a winner: a protein called Archon1.

The researchers then tested Archon1’s ability to measure activity in the brains of mice, zebrafish larvae, and C. elegans. When the neurons in these organisms were active, Archon1 glowed. The brighter the glow, the higher the voltage.

Archon1 can also be used in conjunction with optogenetics. Optogenetics is the process of exposing neurons to certain wavelengths of light to stimulate or suppress their activity. The researchers exposed optogenetically susceptible neurons in C. elegans to blue light, sparking their activity. The activity of these neurons then stimulated the activity of other neurons within their circuit (which were labeled with Archon1). The Archon1 neurons then glowed, indicating that they had been successfully activated by the optogenetically controlled neurons.

Future research will use this imaging technique to study electrical activity in mouse brains as they perform tasks, helping correlate brain activity to behavior.

For more information on this study, check out the paper in Nature Chemical Biology or read the press release from MIT.