Researchers at MIT have developed a new approach to measure electrical activity deep in the brain: using light — an easier, faster, and more informative method than inserting electrodes.

They’ve developed a new light-sensitive protein that can be embedded into neuron membranes, where it emits a fluorescent signal that indicates how much voltage a particular cell is experiencing. This could allow scientists to study how neurons behave, millisecond by millisecond, as the brain performs a particular function.

Better than electrodes. “If you put an electrode in the brain, it’s like trying to understand a phone conversation by hearing only one person talk,” says Edward Boyden*, Ph.D., an associate professor of biological engineering and brain and cognitive sciences at MIT and a pioneer in optogenetics (a technique that allows scientists to control neurons’ electrical activity with light by engineering them to express light-sensitive proteins). Boyden is the senior author of the study, which appears in the Feb. 26 issue of Nature Chemical Biology.
“Now we can record the neural activity of many cells in a neural circuit and hear them as they talk to each other,” he says. The new method is also more effective than current optogenetics methods, which also use light-sensitive proteins to silence or stimulate neuron activity.
“Imaging of neuronal activity using voltage sensors opens up the exciting possibility for simultaneous recordings of large populations of neurons with single-cell single-spike resolution in vivo,” the researchers report in the paper.

Robot-controlled protein evolution. For the past two decades, Boyden and other scientists have sought a way to monitor electrical activity in the brain through optogenetic imaging, instead of recording with electrodes. But fluorescent molecules used for this kind of imaging have been limited in their speed of response, sensitivity to changes in voltage, and resistance to photobleaching (fading caused by exposure to light).

Instead, Boyden and his colleagues built a robot to screen millions of proteins. They generated the appropriate proteins for the traits they wanted by using a process called “directed protein evolution.” To demonstrate the power of this approach, they then narrowed down the evolved protein versions to a top performer, which they called “Archon1.” After the Archon1 gene is delivered into a cell, the expressed Archon1 protein embeds itself into the cell membrane — the ideal place for accurate measurement of a cell’s electrical activity.

Image Credit:  Researchers at MIT

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