Study Unveils Mice That ‘Smell’ Light

Researchers from Harvard and the Cold Spring Harbor Laboratory have engineered a mouse that can “smell” light, which offers a novel approach to studying the science of olfaction.

Published this week in the journal Nature Neuroscience, the study involved transgenic mice whose olfactory neurons are light-sensitive due to a protein called channelrhodoopsin-2.

Though the technique of using light-sensitive proteins to study the brain has existed for a few years, this is the first time that it was studied in the olfactory bulb, the part of the forebrain that detects smells, according to Venkatesh Murthy, a co-author of the paper and a professor of molecular and cellular biology.

“Most people can recognize that lemons, limes, and oranges smell differently, but at the same time they all belong to the citrus family,” Murthy said. “We want to understand how the brain discriminates between particular odors since...there isn’t a way to predict how a molecule smells just by its structure.”

Normally, only neurons that are connected to the retinas respond to light, but the mice were specially made so that the neurons in their olfactory bulbs would also respond when scientists shone light directly on them. This allowed the scientists to bypass the nose in order to study the behavior of the olfactory neurons.

Because smell, compared to sight and hearing, is a relatively slow sense, delivering the odor to the nose in a precise and timely fashion has always remained a challenge for neurobiologists.

The transgenic mice, Murthy said, solve that problem, since the scientists can deliver light in precisely timed bursts and intensities onto the neurons in the olfactory bulb.

The paper also highlights the usefulness of these special mice in studying how neurons code for information.

Neighboring neurons often carry redundant information as a safety net: in case one neuron is damaged, the message can still be relayed. The optimal neural system is one that allows for a balance between redundancy and maximal capacity to hold information, Murthy said.

According to Dinu F. Albeanu, a co-author of the paper and a CSHL fellow, the study examined whether neural outputs believed to be redundant actually serve distinct functions. From the firing patterns, the scientists determined that neurons use both spatial and temporal cues to transmit different information.

“For a particular smell, [neurons] can actually fire at different time points, and the split differences in timing can be used by the [brain] circuit to encode vital information as well,” Albeanu said.

—Staff writer Helen X. Yang can be reached at hxyang@fas.harvard.edu.