Thursday, June 22, 2017

Mouse study suggests how hearing a warning sound turns into fearing it over time

Fluorescent tagging shows the perineuronal nets (in red) surrounding neurons (in green) of mice. Emory researchers identified a role these nets play in "capturing" an auditory fear association.

By Carol Clark

The music from the movie “Jaws” is a sound that many people have learned to associate with a fear of sharks. Just hearing the music can cause the sensation of this fear to surface, but neuroscientists do not have a full understanding of how that process works.

Now an adult mouse model reveals that changes in lattice-like structures in the brain known as perineuronal nets are necessary to “capture” an auditory fear association and “haul” it in as a longer-term memory. The journal Neuron published the findings by scientists at Emory University and McLean Hospital, a Harvard Medical School affiliate.

The findings could aid research into how to help combat veterans suffering from post-traumatic stress disorder (PTSD).

“We’ve identified a new mechanism — involving the regulation of perineuronal nets in an adult auditory cortex — that contributes to learning an association between an auditory warning and a fearful event,” says Robert Liu, a senior author of the study and an Emory biologist focused on how the brain perceives and processes sound. “It’s surprising,” he adds, “because it was previously thought that these perineuronal nets did not change in an adult brain.”

Another novel finding by the researchers: It’s not just activity in the auditory cortex during a fear-inducing experience associated with sound, but after the experience that is important for the consolidation of the memory.

“What is unexpected is that this brain activity was not in direct response to hearing the actual sound, since animals were just sitting in a quiet room during that period,” Liu says. “This finding could fit with an idea that’s been around for some time, that the way your brain consolidates memories of your day’s experiences is by replaying the events after they have happened.”

The amygdala — a region of the brain located within the temporal lobes — has long been tied to learning what stimuli can trigger emotional reactions such as fear. More recent studies have shown the firing of circuits in the auditory cortex during a threatening sound also play a role in learning what signals should set off a fear reaction.

The auditory part of the brain goes from the ear and cochlea through several stages to reach the auditory cortex — the highest neural processing level for sounds.

Perineuronal nets (PNN) are extracellular lattices that surround and stabilize neurons. During childhood development they have plasticity. “When they eventually mature, they crystalize, locking down the anatomy around the neurons and forming a kind of scaffold,” Liu says. “It’s been thought that these nets remained largely stable in adulthood.”

The mice used in the current research were trained to associate the sound of a tone with a mild shock. The animals eventually would freeze when they heard the sound, in anticipation of the mild shock. Days later, they continued to freeze at the sound even when the shock no longer followed it. The researchers found that, after the fear-association experience, a transition period lasting about four hours occured in which the PNN in the rodents’ auditory cortex changed to become stronger.

“We speculate that the strengthening of these nets — just like during development — may be putting a brake on further neural plasticity and ‘locking in’ the fear association before other sound experiences interfere with the memory,” Liu says.

When some mice in the study were given an enzyme that dissolved the PNN in the auditory cortex, they stopped remembering to freeze at the sound of the tone. “We essentially removed these nets and that appeared to prevent the fear association from consolidating in the memory, so it fell away faster,” Liu says. “It’s counterintuitive. Before we would have thought if we removed the PNN it would have increased the potential for learning the fear association by increasing the plasticity of the neurons.”

Such research could aid in the development of an intervention for PTSD. “It suggests that there may be a window of time after someone experiences a trauma that you could give them a drug to silence activity in a particular area of the brain,” Liu says. “That might prevent them from consolidating a particular traumatic memory.”

The findings also add to data about how the brain learns in general, and the relationship between receiving new information and a critical time period needed to consolidate it, he says.

First author of the study is Sunayana Banerjee, who conducted the research while she was a post-doctoral fellow at Emory. Co-senior author is Kerry Ressler – a psychiatrist focused on PTSD who was formerly with the Yerkes National Primate Research Center and Emory University and is now at Mclean Hospital and Harvard Medical School. Co-authors include research specialist Hadj Aoued and Emory undergraduates Vanessa Gutzeit, Justin Baman and Nandini Doshi. The research was supported by the National Institutes of Health grants R21MH102191 and R01DC008343 and the Office of Research Infrastructure Programs’ Primate Centers P51OD11132.

Related:
Sensory connections spill over in synesthesia
Uncovering secrets of sound symbolism

Wednesday, June 21, 2017

Pollinator extinctions alter structure of ecological networks

On the wings of National Pollinator Week, a new study by Emory biologist Berry Brosi gives insights into the dynamics of plant-pollinator interactions.

By Carol Clark

The absence of a single dominant bumblebee species from an ecosystem disrupts foraging patterns among a broad range of remaining pollinators in the system — from other bees to butterflies, beetles and more, field experiments show.

Biology Letters published the research, which may have implications for the survival of both rare wild plants and major food crops as many pollinator species are in decline.

“We see an ecological cascade of effects across the whole pollinator community, fundamentally changing the structure of plant-pollinator interaction networks,” says Berry Brosi, a biologist at Emory University and lead author of the study. “We can see this shift in who visits which plant even in pollinators that are not closely related to the bumblebee species that we remove from the system.” 

If a single, dominant species of bumblebee mainly visits an alpine sunflower, for instance, other pollinators — including other species of bumblebees — are less likely to visit alpine sunflowers. If the dominant bumblebee is removed, however, the dynamic changes.

“When the sunflowers became less crowded and more available, a broader range of pollinators chose to visit them,” Brosi says.

The field experiments, based in the Colorado Rockies, also showed that the removal of a dominant bumblebee species led to fewer plant species being visited on average.

“That was a surprise,” Brosi says. “If a nectar resource is abundant and highly rewarding, more types of pollinators will go for it, leaving out some of the rarer plants that some of the other pollinator species normally specialize in.”

The findings are important since most flowering plants and food crops need pollinators to produce seeds.

“Basically, for almost every pollinator group that we have good data for, we’ve seen declines in those pollinators,” Brosi says. “The results of our field experiments suggest that losses of pollinator species — at a local population level or on a global, true extinction scale — are likely to have bigger impacts on plant populations than previously predicted by simulation models.”

The experiments were done at the Rocky Mountain Biological Laboratory near Crested Butte, Colorado. Located at 9,500 feet, the facility’s subalpine meadows are too high for honeybees, but they are filled with a variety of bumblebees and other pollinators.

The study included a series of 20-meter-square wildflower plots. Each was evaluated in a control state, left in its natural condition, and in a manipulated state, in which bumblebees of just one species had been removed using nets. The bumblebees were later released unharmed when the experiments were over.

The work built on 2013 research led by Brosi that focused on bumblebees and one target plant species, alpine larkspur. That study showed how removing a bumblebee species disrupted floral fidelity, or specialization, among the remaining bees in the system, leading to less successful plant reproduction.

For the current paper, the researchers looked at a system of more than 30 species of pollinators and their interactions with 43 plants species.

“There’s been a lot of observational research done on plant-pollinator networks,” Brosi said. “One of the general findings is that they have a really consistent structure. That tends to hold true almost irrespective of ecosystem and geographic area, from the northeastern coast of Greenland to tropical rainforests.”

Mathematical simulation models have suggested that plant-pollinator networks would have good resiliency if there is an extinction in the system, based on the assumption that the network structure would remain consistent.

“Our experiments show that this assumption is not tenable,” Brosi says. “These networks are dynamic and when a pollinator species is missing, we’re going to see both qualitative and quantitative changes. Future simulation models need to incorporate ecological processes like competition that can shape which pollinators interact with which plants.”

Co-authors of the study are Kyle Niezgoda, who worked on the project as an undergraduate in Emory’s Department of Environmental Sciences, and Heather Briggs of the University of California, Santa Cruz.

Related:
Bees 'betray' their flowers when pollinator species decline
The top 10 policies needed now to protect pollinators

Monday, June 19, 2017

Mutant mosquitos make insecticide-resistance monitoring key to controlling Zika

"You can't stop evolution," Emory disease ecologist Gonzalo Vazquez-Prokopec says, explaining that it is a natural process for mosquitos to mutate in response to insecticides. (CDC photo by James Gathany)

By Carol Clark

One of the most common insecticides used in the battle against the Aedes aegypti mosquito has no measurable impact when applied in communities where the mosquito has built up resistance to it, a study led by Emory University finds.

The study is the first to show how vital insecticide-resistance monitoring is to control the Aedes mosquito — which carries the viruses that cause Zika, dengue fever and yellow fever.

The journal PLoS Neglected Tropical Diseases published the research.

“The results are striking,” says Gonzalo Vazquez-Prokopec, a disease ecologist at Emory and first author of the study. “If you use the insecticide deltamethrin in an area with high-deltamethrin resistance, it’s the same as if you didn’t spray at all. It does not kill the Aedes aegypti mosquitos. The efficacy is not different to a control.”

The results of the randomized, controlled trial are important because some public health departments in places where Zika and dengue viruses are endemic do not necessarily monitor for insecticide resistance.

“The recent epidemic of the Zika virus has raised awareness that we need to focus on what really works when it comes to mosquito control,” Vazquez-Prokopec says. “The data from our study makes a bold statement: Any mosquito-control program involving spraying insecticides needs to be based on knowledge of the current levels of insecticide-resistance of the local mosquitos.”

It is not difficult to determine levels of insecticide resistance, he adds. Public health workers can use standardized bioassays to coat a bottle with an insecticide in a specific dose. They can then introduce mosquitos from the area to be monitored into the bottles and observe the number of them killed after 24 hours.

The current study — conducted in three neighborhoods of Merida, Mexico — measured the efficacy of indoor residual spraying against adult Aedes aegypti mosquitos in houses treated with either deltamethrin (to which the local mosquitos expressed a high degree of resistance) or bendiocarb (another insecticide to which the mosquitos were fully susceptible), as compared to untreated control houses.

The bediocarb-treated areas showed a 60-percent kill rate for Aedes aegypti mosquitos during a three-month period, while the deltamethrin-treated areas and the control areas showed no detectable impact on the mosquitos.

A research technician sprays the ceiling and walls of a home in Merida, Mexico, as part of the first study to show how vital insecticide-resistance monitoring is to control a mosquito that can spread the Zika virus. (Photo by Nsa Dada)

It’s a natural biological process for mosquitos to mutate in response to insecticide exposure, Vazquez-Prokopec says. These mutations can occur at the molecular level, preventing the insecticide from binding to an enzymatic target site. They can also happen at the metabolic level — when a mosquito’s metabolism “up regulates” the production of enzymes that can neutralize the toxic effects of an insecticide.

“Both mechanisms can occur in the same mosquito,” Vazquez-Prokopec says, “making insecticide resistance a challenging and fascinating problem.”

Even more worrying are so-called “super bug” mosquitos, that show resistance to more than one insecticide.

“You can’t stop evolution,” Vazquez-Prokopec says. “That’s why it’s important for countries to have resistance-monitoring systems at both local and national levels to help manage the use of insecticides more efficiently and effectively.”

For the past 20 years, there has been a rise in resistance to insecticides in mosquitos, particularly in the Anopheles genus, some of which transmit the malaria parasite. Anopheles mosquitos only bite between dusk and dawn, so the use of bed nets in areas where malaria is endemic have long been a method to reduce the opportunity for mosquitos to transmit malaria.

More than a decade ago, bed nets treated with pyretheroids — a class of pesticides that includes deltamethrin — were rolled out in Africa in a big way to fight malaria. Pyretheroids are commonly used because they are odorless, cheap, long-lasting and have low mammalian toxicity.

The widespread use of insecticide-treated bed nets eventually led to a rise in resistance to pyretheroids by the Anopheles mosquito. The nets, however, still provide a physical barrier between people and mosquitos so they retain some benefit.

A similar rise in resistance is being seen in the Aedes mosquito in some areas. But the Aedes mosquitos bite during the day, making bed nets ineffective and insecticide spraying campaigns more critical to their control.

Previous research led by Vazquez-Prokopec showed that contact tracing of human cases of dengue fever, combined with indoor residual spraying for Aedes mosquitos in homes, provided a significant reduction in the transmission of dengue during an outbreak.

The insecticide-resistance study adds to the growing body of knowledge of what works — and what doesn’t — to control the Aedes mosquito in order to lessen the impact of a mosquito-borne disease outbreak, or to prevent one altogether.

“We’re always going to be chasing the problem of insecticide resistance in mosquitos, but the more data that we have — and the more tools we have in our arsenal — the more time we can buy,” Vazquez-Prokopec says.

Co-authors of the study include scientists from Mexico’s Autonomous University of Yucat√°n, where Emory has a long-standing collaboration. The work was funded by the Emory Global Health Institute and Marcus Foundation, the Centers for Disease Control and Prevention, Mexico’s CONACYT and the National Health Medical Research Council.

Related:
Contact tracing, with indoor spraying, can curb dengue outbreak
Zeroing in on 'super spreaders' and other hidden patterns of epidemics

Thursday, June 15, 2017

To boldly go where public health hasn't gone before

"Hopefully, Emory will make a mark in NASA history," says Yang Liu, associate professor of environmental health. (NASA photo)

From Rollins Magazine

Rollins School of Public Health researchers will soon take their research into orbit, partnering with the National Aeronautics and Space Administration (NASA) in a new satellite mission to study air pollution.

NASA chose Rollins as a joint recipient of its $100 million award — $2.3 million of which will come to Rollins — to study the effects of air pollution on the population through a satellite mission, according to Yang Liu, associate professor of environmental health. He noted that this is the first time a NASA space mission has incorporated a public health component.

"We're the scientific guinea pig," Liu said.

The Rollins research group, led by Liu, co-created the project idea with NASA's Jet Propulsion Laboratory (JPL). The mission will construct and use a Multi-Angle Imager for Aerosols (MAIA) device to record airborne particulate matter, which will collect data on the effects of pollution on public health from at least 10 locations with major metropolitan areas.

Once constructed by JPL, the MAIA device will be mounted on a compatible Earth-orbiting satellite. "Even though it's a small mission, it's actually the first ever in which we get to work with NASA engineers to build public health into the DNA of this instrument," Liu said.

The Rollins team will analyze the data to make predictions about public health issues such as birth outcomes and cardiovascular disease. The team will also serve as the public health liaison between JPL and other institutions in the complete research group. Recruited by Liu, the complete group has teams at University of California, Los Angeles, Harvard University, University of British Columbia, and University of Dalhousie.

Because the device will orbit via satellite, it will provide a more holistic view of air pollution data than the commonly used ground monitors.

"It's very difficult to cross to a completely different scientific community and convince them that this mission is not only worthwhile but also feasible," Liu said. "Hopefully, Emory will make a mark in NASA history."

Related:
Georgia Climate Project creates state 'climate research roadmap'

Wednesday, June 14, 2017

A disarming comedian interviews an Emory psychologist loaded with facts about the brain

Comedian Jordan Klepper, center, takes a break from filming in the Emory psychology department. He interviewed Emory psychologist Stephan Hamann, left, about the brain science involved in trying to understand the U.S. political divide and culture wars. (Photo by Carol Clark)

By Carol Clark

Why do some people have a liberal mindset while others seem set on conservatism? And what makes it so difficult to find common ground? Those are some of the questions explored in a one-hour special, “Jordan Klepper Solves Guns,” which aired recently on Comedy Central.

Comedian Jordan Klepper and a camera crew came to the Emory campus last October to film part of the program in the Department of Psychology. Klepper interviewed psychologist Stephan Hamann about his research into how the brain may influence whether people are on one end of the political spectrum or the other, and how we might use this knowledge to better understand one another. 

“People develop their beliefs over a lifetime,” Hamann explains, “and when you tell them something that they feel challenges those core beliefs, they can have a threat response and just shut down. Brain research shows how they stop processing information on a rational level and begin operating on a more emotional level. Of course, that’s the exact opposite of what you want them to do.”

The best way to try to discuss an idea that counters someone’s convictions is to go slow and lay the ground work, he adds. “You have to be as empathetic and compassionate as possible. That’s the first step. You have to earn someone’s trust before you jump to the argument.”

Klepper also underwent an fMRI scan of his own brain in Emory’s Facility for Education and Research in Neuroscience (FERN).

“The program did a good job of conveying a little bit of the science involved in brain imaging,” Hamann says. “These are challenging times, so it’s gratifying to be part of something aiming 5o help Americans find common ground. I like the way the program ended on a positive note, trying to get people to connect up with the political process.”

If you missed the broadcast, you can watch it on Klepper’s web site, JordanKlepperSolves.com.