Interactions between neurons involve both chemical and electrical signaling. For decades, neuroscientists have searched for a noninvasive way to measure the electrical component. Achieving this could make it easier to study how the brain works, and how neurological disease impairs its functioning.
One promising approach is tracking neuronal electrical activity with fluorescence, which can be integrated into cells fairly easily through genetics or by being attached to antibodies, but which can be toxic and slow to work. Last week, researchers introduced a new candidate—a fluorescent protein from a Dead Sea microbe—that appears to be better equipped for the challenge.
The protein, called archaerhodopsin-3, or Arch, was discovered more than 10 years ago, but scientists are just now starting to realize its potential as a research tool. In a study published last year, researchers used light to trigger an electrical response from Arch that silenced overactive neurons—an approach that could lead to new therapeutics for epilepsy and other seizure disorders.
In this study, the researchers took the opposite tack and used electricity to elicit changes in Arch’s fluorescence. The approach could lead to more accurate methods for recording electrical signals from the brain.
The results, published in Nature Methods, indicate that Arch could be the noninvasive voltage sensor neuroscientists have been looking for: It’s not toxic to cells, and it’s sensitive and fast enough to pick up the rapid electrical changes that accompany neuronal activity.
“It looks order of magnitudes better than any of the other optical imaging methods I’ve seen before,” says Darcy Peterka, a neuroscientist at Columbia University who was not involved with the study.
The standard method for recording electrical activity in neurons in cell culture—which involves sticking an electrode into the cell—remains the most accurate for measuring voltage at a single point in the cell. But puncturing a neuron with an electrode eventually kills it, whereas Arch would let researchers follow the electrical signal as it propagates throughout the cell. It would also allow researchers to record from the same cell again and again, allowing for long-term experiments that would not be possible with the standard method.
“It really depends on what scientific questions you’re trying to answer,” says Adam Cohen, a biophysics researcher at Harvard University and the lead author of the new study.