New Fluorescent Technique Opens Window on Neuronal Activity

Studying neuronal activity has been difficult due to a lack of methods that provide localized, real time feedback. Researchers at University of California, San Diego School of Medicine have now developed a new technique that utilizes special voltage reactive dyes that only pass through the membrane of neurons. When light is applied to the dyed neurons, they glow slightly more in response. Because former techniques lacked precision, results of multiple experiments had to be averaged out in order to get a clear picture. With the new method, individual experiments on the activity of neurons can be conducted

From the announcement:

“One of the tradeoffs with using voltage-sensing dyes in the past is that when they were reasonably sensitive to voltage changes, they were slow compared to the actual physiological events,” said Miller [Evan W. Miller, a UCSD post-doc]. “The new dye gives big signals but is much faster and doesn’t perturb the neurons. We essentially see no lag time between the optical signal and electrodes (used to double-check neuronal activity).”

The new method provides a wider view of neuronal activity, said Miller. More importantly, it makes it possible for neuroscientists to do accurate, single trial experiments. “Right now, you have to repeat experiments with cells, and then average the results, which is physiologically less relevant and meaningful.”

For Tsien [Roger Tsien, PhD, Howard Hughes Medical Institute investigator, UC San Diego professor of pharmacology, chemistry and biochemistry and 2008 Nobel Prize co-winner in chemistry for his work on green fluorescent protein], the new dyes address a career-long challenge.

“These results are the first demonstration of a new mechanism to sense membrane voltage, which is particularly satisfying to me because this was the first problem I started working on as a graduate student in 1972, with little success back then,” said Tsien. “Later, we devised indirect solutions such as calcium imaging or dyes that gave big but slow responses to voltage. These techniques have been very useful in other areas of biology or in drug screening, but didn’t properly solve the original problem. I think we are finally on the right track, four decades later.”

Press release: New Fluorescent Dyes Highlight Neuronal Activity

Abstract in PNAS: Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires