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.

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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.

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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 Yucatán, 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.

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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."

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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.

The neuroscience of learning across borders

Brains without borders: Emory Laney Graduate School student Charlie Ferris, from psychologist Stephan Hamann's lab, poses with a brain sculpture at the Institute of Neurobiology in Querétaro, Mexico, during the recent Binational Mechanisms of Learning Forum. (Photo by COMEXUS) 

By Carol Clark

Jessica Dugan sits at a computer in the Emory University psychology department in Atlanta, training a rhesus monkey in a lab at a university in Querétaro, Mexico, on the concept of transitive inference. 

She watches the monkey in real-time on her screen. With a few clicks on her keyboard she can present the monkey with random images on a computer attached to its cage and see which image it chooses. The monkey is automatically rewarded with food pellets for correct choices. Eventually, the monkey begins to grasp that the computer “game” is based on a concept of transitive inference — the idea of a hierarchy based on a shared property.

“It’s pretty cool,” Dugan says. “As long as there’s a wi-fi connection, we can remotely put a monkey on task and conduct a training exercise or an experiment. Technology can make collaboration across countries a lot easier.”

The joint project between Emory and the National Autonomous University of Mexico (UNAM) Institute for Neurobiology is just one more in a series of doors opening for Dugan, leading to new ways of learning science and conducting research.

She entered Emory’s Laney Graduate School under the mentorship of psychologist Patricia Bauer, who focuses on human development of memory from infancy through childhood. Dugan is particularly passionate about designing and conducting experiments with children to get at some of the key questions surrounding metacognition — introspection about thought processes.

“Basically, I’m interested in how someone thinking about thinking may be able to improve their ability to learn new information,” she explains. “Self-generation of new knowledge is something that we use every day. It’s a process that’s critical to success in education and beyond.”

Dugan is simultaneously working with rhesus monkeys in the lab of Emory psychologist Robert Hampton. “Studying the cognition of the relatives of our earliest ancestors may help us understand if there was some evolutionary demand that led to us being able to perform certain cognitive tasks,” she says.

And now she’s broadened her horizons by working across countries through the UNAM collaboration.

In May, Dugan was part of a group of 15 Emory graduate students who traveled to Mexico for the UNAM Binational Mechanisms of Learning Forum. The forum was the capstone of a year-long graduate seminar held at both Emory and UNAM called “Mechanisms of Learning Across Species and Development.”

Emory psychologist Patricia Bauer, left, listens as Maria Jose Olvera, a graduate student from the Institute of Neurobiology, explains her research. (Photo by COMEXUS)

“It was an amazing experience,” Dugan says of the nearly week-long forum. “The neuroscience they are doing in Mexico is impressive. It makes me wonder why in the United States we tend to mainly focus on science done here or in Europe. It was as though I was watching a documentary about the cosmos and someone started describing our place on Earth and the camera zoomed out so you realized how small that we are. The Mexico forum gave me a much more universal perspective.”

“We want our students to have an international appreciation for science, so they’re not so America-centric,” Bauer says. “There are lots of things to learn from other parts of the world.”

Bauer co-taught the Mechanisms of Learning seminar in Atlanta this year with Emory psychologist Joseph Manns, and both also traveled to Mexico to participate in the forum. 

Meanwhile, Hampton co-taught the seminar to graduate students in Mexico with UNAM neuroscientist Hugo Merchant, who also researches rhesus monkeys. Hampton is on sabbatical from Emory and has been living in Querétaro and working at the Institute of Neurobiology for the past academic year, funded by the Fulbright Scholars Program.

“The idea is not just to exchange information that makes our science stronger,” Hampton says. “Mexico is a country with a huge border with the United States. We need to have more contact with one another so that we understand each other better and reduce the potential for conflicts between our two countries.”

Emory graduate student Kelly Chong, a member of the lab of biologist Robert Liu, discusses her research with Arturo Gonzalez Isla, a graduate student at the Institute of Neurobiology in Mexico. (Photo by COMEXUS)

UNAM, based in Mexico City, is one of the largest universities in the world, with nearly 400,000 students and faculty. Its Institute for Neurobiology is about three hours north in Querétaro, a small but growing city in the highlands of central Mexico.

“The air is a little bit thinner and the sun’s a bit stronger than in Atlanta,” Hampton says. “It’s ‘tranquillo’ — a calm place — with a high quality of life.”

The institute “is doing the full spectrum of neuroscience,” he adds, “from high-level primate cognition work to molecular biology, neuroanatomy, neurodevelopment and more.”

While most classes are taught in Spanish, the Mexican students are required to both read and publish scientific papers in English.

Emory has hosted the Mechanisms of Learning Forum for the past three years as a capstone to the graduate seminar and as part of a training program co-directed by Bauer and Hampton, funded by the National Institutes of Health.

This year, with Hampton based in Mexico, the decision was made to hold the forum in Querétaro, with funding from the Institute of Neurobiology and Emory's Halle Institute, Department of Psychology and Emory College. The U.S. Embassy in Mexico, Mexico’s National Association of Universities and Institutions of Higher Education (ANUIES), and COMEXUS — the Fulbright Scholars Program supporting Hampton’s sabbatical — also pitched in to support the event.

Thirty-three graduate students from the U.S. and Mexico came together with nine faculty guest speakers from institutions in both countries to discuss their work. The speakers covered topics ranging from human language learning, avian song learning, rodent motor learning and the electrophysiology of memory in adult humans.

“It was a phenomenal opportunity,” says Emory graduate student Emily Brown, who had never been to Mexico. “The best part of the experience for me was meeting the other graduate students and expanding my scientific network to another country. It was neat to see that they are facing similar challenges as graduate students in the United States, and doing similar research.”

A central part of the forum is an open-ended hypothesis-generating exercise. “You get together with people from different backgrounds whom you don’t normally get to bounce ideas off,” Brown explains. “It’s a chance to play with ideas across boundaries and disciplines. The aim is to be creative and to not reject something that may sound a little crazy at first. Instead, you brainstorm about possible techniques or strategies that might make it work. It’s expansive thinking that you don’t necessarily get to do on a day-to-day basis.”

“It’s a great exercise,” Dugan adds, “because as a graduate student you spend a lot of time cranking out things that have to be immediately useful. You can get stuck in a mindset of what won’t work. It’s beneficial to get together with people who have different passions and just think creatively.”

Emory graduate student Emily Brown in the Advanced Facility for Avian Research in Ontario with one of her research subjects — a black-capped chickadee. "The people more likely to make the big discoveries are those willing to talk to each other across labs, institutions and countries," Brown says.

Creative thinking has already led Brown into unexpected places. She began her graduate school career studying memory systems of rhesus monkeys in the Hampton lab, and thought she would stick to that path. Then she began hearing about memory work with wild birds and proposed a research project in collaboration with Hampton and Emory psychologist Donna Maney, who is focused on how genes, hormones and the environment affects the brains of birds.

One of the guest speakers at the 2014 Mechanisms of Learning Forum was David Sherry, an expert on bird cognition from the University of Western Ontario’s Advanced Facility for Avian Research in London, Ontario. Brown was inspired by his talk and ultimately able to expand her collaboration to include Sherry. She is now continuing as a graduate student at Emory while in the Sherry lab in Canada.

“It’s one of the top avian research facilities in the world,” Brown says. “I’m developing a technique to study memory and cognition in wild, free-living birds. Right now, I’m working with black-capped chickadees, which are known for taking bits of food, hiding them for later, and then using their memory to locate them. Ideally, the techniques I’m developing could be used with any small songbirds that you see coming to a feeder in your yard.”

Birds make a good model species because they are so widespread and their behavior in the wild is well-documented, she says. “You have some bird species that are closely related living in dramatically different ecosystems and those that are not closely related at all operating in similar ecosystems. So you can compare which cognitive functions of species might be more driven by the environment and the pressures that they’re facing there.”

Adding Mexico to the mix of her graduate school experiences seemed like a natural progression to Brown. “Scientists are doing science everywhere and we shouldn’t be closed off to each other because of some borders on a map,” she says. “Science is advanced by communication. The people more likely to make the big discoveries are those willing to talk to each other across labs, institutions and countries.”

And the talk doesn’t always have to be about work.

A highlight for Brown in Mexico was a social outing — a hike through a wildlife preserve with the host students. “I had a chance to see a lot of the local flora and fauna,” she says. “It’s a really different ecosystem than Atlanta or Ontario. It’s dry, full of cactuses and vermillion flycatchers. They’re very pretty birds.”

Dugan agrees that breaking down barriers is important to the future of science. “The science community is all over the world,” she says. “Science in general is in jeopardy right now but we’re stronger together. People around the world are benefitting from — and contributing to — scientific progress.”

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Students advocating for academic science

Students advocating for academic science

PhD candidates Crystal Grant, left, and Joshua Lewis are vocal advocates for scientific research at universities, but neither is ready to commit to academic careers due to uncertainty about good jobs. Last summer, they made their case to congressional aides from the Georgia delegation. (Kay Hinton)

By Hal Jacobs
Emory Magazine

Call it the 800-pound gorilla in the lab.

Crystal Grant, a graduate student in Emory's Genetics and Molecular Biology program in the Graduate Division of Biological and Biomedical Sciences (GDBBS), faced it while studying how people’s DNA changes with age.

Graduate student Joshua Lewis of the GDBBS Biochemistry, Cell and Developmental Biology program saw its shadow while researching how cells stick to neighbor cells— information that could lead to understanding how cancer cells metastasize.

The problem weighed so heavily on Chelsey Ruppersburg, who graduated with a PhD in 2016, that she changed career directions after racing to earn a doctorate in cell biology in only four years, rather than the usual six or seven.

The situation is readily apparent to anyone who works in an academic lab. Research is a slow, steady, incremental process; funding is erratic, inconsistent, boom and bust. Principal investigators must tear themselves away from working with students to chase fewer National Institutes of Health (NIH) and National Science Foundation (NSF) grants. Hiring new students and staff is fraught because funding for their positions is a moving target.

Meanwhile, a steady stream of graduate students—vital to every academic lab—compete for rarer faculty positions while being tempted by more lucrative private industry jobs or opportunities abroad.
Postdoctoral fellowships, an important transitional step from student to professor, have become a port of call that may stretch into years of low pay and uncertainty for scientists who hoped to settle down after a decade-plus of intense schooling.

But as the challenge grows steeper, the same young scientists who are most affected are also trying to solve it.

Read more in Emory Magazine.

Key connection in neural code of 'love' uncovered in vole study

New research probes the neural circuitry responsible for pair bonding in prairie voles.

From Woodruff Health Sciences

A team of neuroscientists from Emory University's Silvio O. Conte Center for Oxytocin and Social Cognition has discovered a key connection between areas of the adult female prairie vole's brain reward system that promotes the emergence of pair bonds. Results from this study, published this week in Nature, could help efforts to improve social abilities in human disorders with impaired social function, such as autism.

This Conte Center study is the first to find the strength of communication between parts of a corticostriatal circuit in the brain predicts how quickly each female prairie vole becomes affiliative with her partner; prairie voles are socially monogamous and form lifelong bonds with their partners. Additionally, when researchers boosted the communication by using light pulses, the females increased their affiliation toward males, thus further demonstrating the importance of this circuit's activity to pair bonding in prairie voles.

"Prairie voles were critical to our team's findings because studying pair bonding in humans has been traditionally difficult," says co-lead author Elizabeth Amadei. "As humans, we know the feelings we get when we view images of our romantic partners, but, until now, we haven't known how the brain's reward system works to lead to those feelings and to the voles' pair bonding."

Building upon previous work in prairie voles that demonstrated brain chemicals, such as oxytocin and dopamine, act within the medial prefrontal cortex and nucleus accumbens to establish a pair bond, the team set out to address finding the precise neural activity leading to a pair bond. The researchers used probes to listen to neural communication between these two brain regions and then analyzed activity from individual female prairie voles as they spent hours socializing with a male - a cohabitation period that normally leads to a pair bond.

The team discovered that during pair bond formation, the prefrontal cortex, an area involved in decision-making, helps control the rhythmic oscillations of neurons within the nucleus accumbens, the central hub of the brain's reward system. This suggests a functional connection from the cortex shapes neurons activity in the nucleus accumbens.

The team then noticed individual voles varied in the strength of this functional connectivity. Importantly, each subject with stronger connectivity showed more rapid affiliative behavior with her partner, measured as side-by-side huddling contact. Furthermore, the pair's first mating, a behavior that accelerates bonding in voles, strengthened this functional connection, and the amount of strengthening correlated with how quickly the animals subsequently huddled.

"It is remarkable there are neural signatures of a predisposition to begin huddling with the partner. Similar variation in corticostriatal communication could underlie individual differences in social competencies in psychiatric disorders in humans, and enhancing that communication could improve social function in disorders such as autism," says Larry Young, co-author and director of the Conte Center and chief of the Division of Behavioral Neuroscience and Psychiatric Disorders at Yerkes National Primate Research Center.

The study results led the team to ask more questions, including whether communication between the prefrontal cortex and nucleus accumbens not only correlates with huddling but also causally facilitates it. To answer this, the researchers used optogenetics, a technique that allowed them to enhance communication between the brain areas using light, and enhanced communication between the prefrontal cortex and nucleus accumbens of female voles during a brief cohabitation without mating, which is not conducive to pair bonding.

The team discovered optogenetically stimulated animals showed greater preference toward partners compared to a stranger male when given a choice the following day.

"It is amazing to think we could influence social bonding by stimulating this brain circuit with a remotely controlled light implanted into the brain," says Zack Johnson, co-lead author. The study results identify an important reward circuit in the brain that is activated during social interactions to facilitate bond formation in voles.

"Now, we want to know if oxytocin regulates functional connectivity and how circuit activity changes the way the brain processes social information about a partner," says senior author Robert Liu, associate professor in Emory's Department of Biology. "Our team's work is an example of a larger effort in neuroscience to better quantify how brain circuits function during natural social behaviors. Our goal is to promote better neural communication to boost social cognition in disorders such as autism, in which social functioning can be impaired," Liu adds.

Amadei and Johnson were both graduate students who attained their PhD's this year. Additional Emory-based co-authors are graduate students Yong Jun Kwon and Varun Saravanan, undergraduate student Aaron Shpiner, and Wittney Mays, Steven Ryan, PhD, Hasse Walum, PhD, and Donald Rainnie, PhD.

The goal of the Silvio O. Conte Center for Oxytocin and Social Cognition is to improve human health by leading coordinated and rigorous research programs to discover the neural mechanisms by which oxytocin modulates social cognition. The research represents a unique collaboration among Emory University's Emory College of Arts and Sciences, School of Medicine and Yerkes National Primate Research Center, and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University.

Georgia Climate Project creates state 'climate research roadmap'

Environmental sciences instructor Daniel Rochberg, chief strategy officer for Climate@Emory, says the Georgia Climate Research Roadmap aims to create "Georgia's Top 40," a set of targeted research questions to help the state understand and address climate change. (Emory Photo/Video)

By Kimber Williams
Emory Report

Scientists, researchers and environmental experts from across the state convened at Emory last week to draft the “Georgia Climate Research Roadmap” — a set of targeted research questions that could help Georgia better understand and address one of the century’s defining challenges.

The goal of the May 22-23 gathering was to formulate “Georgia’s Top 40,” key climate research questions that could eventually aid decision-making and planning for Georgia policymakers, scientists, communities and service organizations.

An initiative of the Georgia Climate Project, the roadmap was a response to the fact that communities across Georgia are already exploring strategies to address the impact of climate change, says Daniel Rochberg, chief strategy officer for the Climate@Emory initiative and an instructor in the Rollins School of Public Health and Emory College of Arts and Sciences, where he focuses on climate change and sustainable development.

Some Georgia communities are actively assessing vulnerabilities and strategies to build resilience to potential climate change impact, while others are developing technologies and policies to begin reducing emissions, according to Rochberg, who has also worked for the U.S. State Department as special assistant to the lead U.S. climate negotiators under presidents Bush and Obama.

“To inform this work, decision-makers at all levels need credible and relevant information from across the natural, applied and social sciences,” says Murray Rudd, an associate professor in Emory’s Department of Environmental Sciences and member of the climate research roadmap steering committee. “The Georgia Climate Research Roadmap seeks to fulfill this need by identifying the key research questions that, if answered, can lay the groundwork for the state and its residents to take effective, science-based climate action,” he says.

Read the full story in Emory Report.

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