In 2011, Nashville experienced the emergence of a brood of 13 year cicadas, known as Brood XIX. After spending the majority of their lives underground these bugs, from the genus Magicicada, emerge in huge numbers in the early spring to breed and then are gone almost as quickly as they came. During the time of Brood XIX, walking to lab meant running into several of the bugs on the way (more precisely, them flying into our faces), seeing tons of shed pupal cases around the bases of trees, and trying to keep our dog from eating the live bugs. Some of my adventurous classmates cooked them up, while the more entomologically minded collected them for further study.
If you have scratched a mosquito bite, then you have experienced one itchy consequence of the mosquito’s sensitive sense of smell, known as olfaction.
Mosquitos and other insects use special odor-sensing nerve cells (olfactory neurons) in their antennae to find egg-laying sites and blood meal sources. Channels in the olfactory neurons, called odorant receptors, bind to smell-causing chemicals known as odorants. Once the channel binds and responds to an odorant, the neuron signals to the brain that an attractive or repulsive scent is close by.
“This paper identifies new chemical tools that people in insect olfaction research can use to study olfactory receptors better. A lot of the tools that are out there now are generic channel blockers,” said Pask. The work, funded by the NIH, gives scientists studying insect olfaction more specific ways to block olfactory receptors to better study how they work. Understanding mosquito odorant receptor function could decrease the spread of disease by discovering ways to prevent mosquitos from smelling and detecting humans as blood meal sources.
In the study, Pask and his co-authors treated cells, possessing an insect odorant receptor and a necessary co-receptor on their surfaces, with some of the thousands of drugs from a chemical compound library. By inserting a tiny electrode into the cells, they measured changes in current, which represent the cell’s response to the chemicals.
When the team exposed the cells to a known activating compound (the agonist), they observed a typical, high activation response. When they used the agonist and added amiloride or one of its more efficient family members, however, the cells showed an unusually low activation response. The data suggest that these compounds block the ability of the odorant receptor to respond to odorants. If the channel cannot respond, the neuron will not signal to the bug’s brain about important smells nearby.
So are amiloride-like compounds going to show up in your bug spray? “The issue with these molecules is they’re not volatile [able to be vaporized], so you couldn’t cover yourself with them,” said Pask. “At this point, their main use is in basic research and understanding how odorant receptors work.”
In terms of the global health impacts of understanding insect olfaction, Pask said, “The mosquito uses its olfactory system to locate not only human hosts, but also where a good site is to lay their eggs and where to find flowers and fruits for nectar feeding. If you could block their ability to sense these things, they would have to rely on other pathways to find the things they need.”
Manipulating mosquito olfaction could have extraordinary effects on human health. According to the Bill & Melinda Gates Foundation, mosquito-borne malaria kills almost 1 million people per year. Dengue virus, also transmitted by mosquitos, requires hospitalization for approximately 500,000 people per year, as reported by the World Health Organization. Mosquito saliva carries and passes both the malaria parasite and dengue virus to people during blood meals.
The influence of amiloride on insect olfaction research extends beyond global health. Olfaction plays a large role in crop damage caused by insects. Pask’s research showed that odorant receptors from agricultural pests (western tarnished plant bug and tobacco budworm, a moth) are also blocked by amiloride and related compounds.
“The agricultural component is huge as far as moth pests. Usually it’s not the adult moths that are destructive; it’s the moth larvae. So if you can control where they lay their eggs, then you can push them away from your crop,” Pask said. Insect olfaction is essential in female choice of egg-laying sites. Using amiloride family members to study olfaction in this context may therefore have positive agricultural implications.
So what comes next in studying insect olfaction? It turns out that odorant receptors are not the only receptors that contribute to olfaction. “There is also another set of receptors called the IRs,” Pask said. IR stands for ionotropic receptor, and the role of IRs in insect olfaction is not well understood. Though little is known about IRs, the amiloride compound family has the potential to block their function, further demonstrating the power of this new tool for understanding insect olfaction in the future.
Healthy new moms are less focused on non-baby stresses than women that are not mothers.
“We were interested in trying to understand why new mothers seem less stressed out,” says neuroscientist Heather A. Rupp of the Kinsey Institute for Research in Sex, Gender, and Reproduction. Rupp and her colleagues from the Kinsey Institute and the University of Zurich published the results of their study September 6 online in Social Cognitive and Affective Neuroscience.
Rupp and colleagues guessed that the hormone oxytocin might regulate the decreased response to stress in new mothers’ brains. They used functional MRI, an imaging technique that correlates activation in different brain areas to changes in blood flow, and compared the brains of non-mothers to mothers while the groups of women looked at emotionally-evocative negative images. They also exposed a subset of both groups to oxytocin via nasal spray.
One part of the brain, the right amygdala, was less responsive to the negative images in the moms than the non-moms, but only in the women that did not receive oxytocin. When the women received oxytocin, the brains of both moms and non-moms showed no difference in the right amygdala, with both groups showing fairly low activation.
When the team initially designed the study, Rupp “had high hopes that the oxytocin nasal spray would have really strong effects,” thus a lack of activation difference in the moms and non-moms who received the hormone raises questions worth investigating. According to Rupp, the effects of oxytocin turn out to be “more interesting and complex” than previously believed.
Most hormones are thought to function immediately and with predictable outcomes. Rupp notes, “With this study and some other work since then, it becomes a lot more clear that oxytocin’s role is very much modulated by the social context and the environment of the individual.” Understanding the window of time during which oxytocin functions as well as its social and environmental influences are obvious future directions for study.
In the case of the brains of the new mothers, their amygdalae might not have responded to the oxytocin because the hormonal environment had already been altered through the processes of carrying, birthing, and caring for their babies. Perhaps their brains were already saturated with oxytocin. Alternatively, the amygdala’s ability to respond might have shifted because the landscape of proteins responsible for recognizing the hormone changed.
The take home message, though, is that healthy women who have recently given birth have a buffered response to stress as compared to non-mothers. “This reduction in stress in healthy moms might have implications for women who have postpartum depression or anxiety disorders, which could help in treating them,” Rupp says.
Rupp predicts that the brains of women with postpartum depression would react to stress similarly to the brains of non-moms. Therefore, increasing oxytocin, either synthetically or in natural ways like getting a massage, may turn out to be an effective treatment for postpartum depression.