Flipping the Switch

research highlights BIoloGICAL TECHNIQUES Stop and smell the geosmin Chin, S.G. et al. Cell Rep. 24, 1667–1678 (2018). Petrichor, the distinct way that dry earth sensitive and light runs the risk of The results were negative, in the smells after it rains, comes in part from overstimulating them; that can effectively aversive sense. Flies with different neurons bacteria in the soil that release a chemical turn a neuron of interest “off” instead of expressing the Or56a receptor were odorant called geosmin. The human nose “on.” Using an odor to test neurons related generally less likely to choose the geosmin- is quite sensitive to the odor, as is that of to an animal’s sense of smell is also more scented well. In fact, “there was no olfactory the fruit fly, Drosophila melanogaster. The natural. Odors are complex—a plume of a neuron that, when activated by itself, would unique way that Drosophila senses geosmin scent will have areas of high concentration give rise to a positive response,” says Potter. is lending itself to a new approach for and low that the brain is designed to “That was kind of surprising—we thought manipulating neurons. interpret. Olfactogenetics can capture those we would see both.” Christopher Potter, a neuroscientist dynamic properties, he says. With their new tool in hand, the Potter at Johns Hopkins University who studies The hardest part was just getting their fly lab wants to dig into questions that were olfaction, works with the fruit fly “to lines ready, Potter recalls. They first had to difficult to ask before in a systematic, figure out essentially how the nose knows get rid of the Or56a receptors that naturally neuron-by-neuron way. For example, how what’s going on in the world.” It’s a research exist in the fly, in order to have a mutant line does the sense of smell influence other topic that’s not always so easy to study that would lack any wild-type response to complex behaviors, like mating? “With because an animal’s sense of smell is a bit geosmin. From there, they then had to add the olfactogenetics approach, I think the messy, he says. Odors activate olfactory the receptors to the specific fly neurons they strength of it is that it does allow you to now receptor neurons in the brain—humans wanted to target. see how different sensory modalities are have 388 different types, fruit flies just Going in, they weren’t entirely sure how working together, influencing the behavior,” 62—but it’s not a 1:1 relationship. well the receptor would work when they Potter says. “It just makes it easier to At least not usually. moved it around, Potter says. Different activate an olfactory neuron in these But a few years ago, Lund University types of olfactory neurons are found in different contexts.” researcher Marcus Stensmyr made an different types of specialized sensory hairs, “Although we have other means of unusual discovery about the fly’s olfactory called sensilla. The geosmin receptor occurs activating neurons, notably through system (Cell 151, 1345–1357; 2012). “He naturally in one type of sensillum, but the fly so-called optogenetics, the ability to use a identified that this odor, geosmin, only has three others that vary in shape and where specific odor to do the same trick is a much activates a single odorant receptor in they are found on the animal’s antenna. welcome addition to the tool-box,” says Drosophila,” says Potter; the receptor is But in the end, Or56a proved quite Stensmyr. “For studies relating to the sense called Or56a. “That caught our attention mobile. After a puff of geosmin, the of smell, and its neural basis in insects, because it’s very unusual. It’s just weird.” researchers saw an electrophysiological I’m confident olfactogenetics will prove But it got the lab thinking: what if they response everywhere they placed the itself most useful.” could take Or56a and express it elsewhere? receptor. The response was stronger in It’s an approach Potter hopes others will They came up with the idea of some neurons than others, but it could be able to easily pick up. The lab has made “olfactogenetics.” It’s similar in principle be improved by increasing the concentration all the reagents and fly lines they developed to optogenetics, an approach Potter of geosmin. freely available, and geosmin itself is had been trying with Drosophila but to In the initial assay they tested, a T-maze relatively cheap, Potter says, especially underwhelming results. Rather than two-choice assay, the results were variable compared to optogenetics equipment. using light to stimulate a specific neuron, and not very robust, Potter says. Activating In theory, olfactogenetics could potentially olfactogenetics uses an odor—geosmin. a single neuron didn’t seem to do much to work in other animals too, if a similar “What Potter and his colleagues have attract or repulse the flies from otherwise odor-odorant receptor pair is known. done is to exploit the innate olfactory empty vials. Wanting to add a little context “The strategy is probably adaptable, but preference of the fly and turn that into a and create a more biologically relevant I think the particular players would be clever tool,” comments Stensmyr, who was situation for their flies, they developed a different,” Potter says. not involved in the current study. “That new ovipositioning assay to test whether A refreshing scent indeed. geosmin, and its super specific receptor activating different olfactory neurons in could be used in this fashion never crossed a gravid female fly influenced where she Ellen P. Nef my mind when we first discovered this decided to lay her eggs. The flies were sensory pathway.” offered three wells filled with agarose to Olfactogenetics has two advantages, choose from: two were odorless while the Published online: 24 September 2018 Potter says. Olfactory neurons are quite third contained geosmin. https://doi.org/10.1038/s41684-018-0161-1 270 LAB ANIMAL | VOL 47 | OCTOBER 2018 | 267–272 | www.nature.com/laban.

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