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.
Light up: Applying voltage to the neurons shown here caused an increase in fluorescence.
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.
The study was conducted in cultured mouse neurons, but Cohen and his
colleagues plan to use Arch to measure neuronal activity in live
animals, starting with simple organisms, such as the zebrafish and the
worm C. elegans. One advantage of these animals is that they're
transparent, making it easy to see the fluorescent signal through a
microscope.
Arch could also prove useful for imaging electrical signals in the
mammalian brain, especially for experiments in mice, which could be
genetically engineered to express the protein in specific neurons or at
specific times in development, for example.
The challenge of transferring the approach to animals is making sure
the fluorescent signal stays strong and consistent. "In the living
brain, light gets absorbed—for example, by blood—so you lose light,"
says Ed Boyden, the researcher at MIT who led the study that used Arch to silence neurons.
The fluorescence given off by Arch also isn't as bright as some of
the other available dyes, but its low toxicity makes this less of a
concern, because researchers could compensate by using higher
concentrations. "The fact that they got it to work well in mouse neurons
bodes well," says Peterka.
By Erica Westly
From Technology Review
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