'Love hormone' guides young songbirds in choice of 'voice coach'

Zebra finches are highly social birds and will press a lever in order to hear a recording of another Zebra finch singing. (Photo by Carlos Rodríguez-Saltos)

By Carol Clark

Oxytocin, the so-called “love hormone,” plays a key role in the process of how a young zebra finch learns to sing by imitating its elders, suggests a new study by neuroscientists at Emory University. Scientific Reports published the findings, which add to the understanding of the neurochemistry of social learning. 

“We found that the oxytocin system is involved from an early age in male zebra finches learning song,” says Natalie Pilgeram, first author of the study and an Emory PhD candidate in psychology. “It’s basic science that may lead to insights into the process of vocal learning across the animal kingdom, including humans.” 

“Our results suggest that the neurochemistry of early social bonds, particularly during language learning, may be relevant in studies of autism,” adds Donna Maney, a professor of neuroscience in Emory’s Department of Psychology and senior author of the study. 

Young male zebra finches learn to sing by listening to an adult male tutor that they choose to pay close attention to, normally their biological father or a “foster” father who nurtures them. This social process holds some similarities for how children learn to speak, making the birds a laboratory model for the neural underpinnings of social vocal learning. 

In the current paper, the researchers show how oxytocin, a hormone essential to social bonding, influences young finches exposed only to the songs of unfamiliar males. In experiments, blocking the young birds’ oxytocin receptors while they listened to a male biased the birds against that male’s song. Instead they preferred to listen to and eventually learn the song of a male they heard when their oxytocin receptors were allowed to function normally. 

The paper builds on previous work by the Maney lab regarding the hormonal and genetic influences on social behavior. Her lab is working with researchers at the Marcus Autism Center in Atlanta to maximize any potential translational impact of its research findings. 

Finding their voice 

Zebra finches are highly social birds. In the wild they nest together in large colonies. Only adult males sing, primarily to court females. 

From the time they hatch, the males begin listening for song, and memorizing particular songs, even before they can actually sing one. “Up until around day 50, they are making little cheeps and warbles, what we call ‘subsong,’” Pilgeram explains. “It’s similar to human infants who begin to babble at around six months without actually talking.” 

During this sensitive listening phase, a male zebra finch pays closest attention to the song of its father, even though it can hear other adult males nearby. 

In a laboratory environment, research shows that if a biological father is removed from a cage before a male hatches and then substituted with a “foster father” that they can interact with, the young male will prefer the song of the foster father over other males it can hear. The young males demonstrate this preference by pressing levers that allow them to hear playback of different songs. 

Learning from their environment 

“The young birds have got to learn all that they can from their environment,” Pilgeram says. “Just as during human development, the birds pay the closest attention to their immediate caregivers, on whom they rely for everything.” 

Around day 50, the young male finches enter puberty and what is called the “plastic song phase.” During this time, they practice their song motor skills and actively try to produce song. Although they begin to shift their attention away from their fathers and show a preference for hearing songs of other males, each young male still practices dad’s tune. 

By day 100, most male zebra finches are fully singing their father’s song. They have reached adulthood and their tune has “crystalized” into the song that they will sing for the rest of their lives. 

In previous research, the Maney lab found that the stronger the preference a male zebra finch shows for its father’s song during the early listening phase, the more closely its crystalized adult song will mimic that of the father. 

The role of oxytocin 

For the current paper, the researchers wanted to test whether the oxytocin system played a role in that preference. 

The research centered on male juvenile zebra finches hatched in the lab. At day four, the fathers were removed from each of the youngsters’ cages so they were raised only by their mothers. The cages were enclosed in chambers that prevented the young birds from hearing song from other birds housed nearby. 

Beginning at day 27 in a young bird’s life, it was exposed to a series of tutoring sessions by two different adult male tutors that it had never heard. The tutor’s cage was placed next to the cage of the young bird, or pupil. When it was exposed to one of the tutors, the pupil was given a substance that blocked its oxytocin receptors from activating. When the young bird was exposed to the other tutor it received a control substance that allowed its oxytocin receptors to function normally. 

After completing a series of tutoring sessions, the pupils were presented with two different levers they could press in their cages. Pressing one lever was more likely to play the song they heard when their oxytocin receptors were blocked. The other lever was more likely to play the song they heard with normally functioning oxytocin. 

The results showed that early in their development, the juveniles favored the song that they heard when their oxytocin was not blocked. 

Building on past findings 

“We also found that when their oxytocin was not blocked, the birds’ developmental milestones fit the same data curve as in our previous research,” Maney says. “They showed an early preference for the song of one tutor, then switched to preferring the other song during puberty.” 

The preference flattened out as they began singing the song of their chosen tutor, she adds. And the stronger the preference that they showed for the chosen tutor’s song during the early listening phase, the more closely their own adult song resembled that of the chosen tutor. 

The researchers also noted behavioral differences in the way the pupils and tutors interacted. With normally functioning oxytocin, a pupil pecked more often at the wall of its cage facing the tutor and more often preened in a fashion known to be associated with focused listening in the birds, compared to when its oxytocin was blocked. 

“Our results suggest that the oxytocin system is involved in how an animal decides where to focus its attention very early in its life,” Pilgeram says. 

Co-authors of the study include Carlos Rodríguez-Saltos, who received his doctorate from Emory and is now at Illinois State University; postdoctoral fellow Nicole Baran; research technicians Matthew Davis and Erik Iverson; and Emory undergraduates Sumin Lee, Emily Kim and Aditya Bhise. 

The work was funded by the National Science Foundation and the Silvio O. Conte Center for Oxytocin and Social Cognition. 

Related:

How a single gene drives aggression in songbirds 

Songbird data yields new theory for learning sensorimotor skills

As the worm turns: New twists in behavioral association theories

The researchers conducted experiments on C. elegans, a roundworm with just 300 neurons, that offers a simple laboratory model for studying how an animal learns.

By Carol Clark

Physicists have developed a dynamical model of animal behavior that may explain some mysteries surrounding associative learning going back to Pavlov’s dogs. The Proceedings of the National Academy of Sciences (PNAS) published the findings, based on experiments on a common laboratory organism, the roundworm C. elegans. 

“We showed how learned associations are not mediated by just the strength of an association, but by multiple, nearly independent pathways — at least in the worms,” says Ilya Nemenman, an Emory professor of physics and biology whose lab led the theoretical analyses for the paper. “We expect that similar results will hold for larger animals as well, including maybe in humans.” 

“Our model is dynamical and multi-dimensional,” adds William Ryu, an associate professor of physics at the Donnelly Centre at the University of Toronto, whose lab led the experimental work. “It explains why this example of associative learning is not as simple as forming a single positive memory. Instead, it’s a continuous interplay between positive and negative associations that are happening at the same time.” 

First author of the paper is Ahmed Roman, who worked on the project as an Emory graduate student and is now a postdoctoral fellow at the Broad Institute. Konstaintine Palanski, a former graduate student at the University of Toronto, is also an author. 

The conditioned reflex

More than 100 years ago, Ivan Pavlov discovered the “conditioned reflex” in animals through his experiments on dogs. For example, after a dog was trained to associate a sound with the subsequent arrival of food, the dog would start to salivate when it heard the sound, even before the food appeared. 

About 70 years later, psychologists built on Pavlov’s insights to develop the Rescorla-Wagner model of classical conditioning. This mathematical model describes conditioned associations by their time-dependent strength. That strength increases when the conditioned stimulus (in Pavlov dog’s case the sound) can be used by the animal to decrease the surprise in the arrival of the unconditioned response (the food). 

Such insights helped set the stage for modern theories of reinforcement learning in animals, which in turn enabled reinforcement learning algorithms in artificial intelligence systems. But many mysteries remain, including some related to Pavlov’s original experiments. 

After Pavlov trained dogs to associate the sound of a bell with food he would then repeatedly expose them to the bell without food. During the first few trials without food, the dogs continued to salivate when the bell rang. If the trials continued long enough, the dogs “unlearned” and stopped salivating in response to the bell. The association was said to be “extinguished.” 

Pavlov discovered, however, that if he waited a while and then retested the dogs, they would once again salivate in response to the bell, even if no food was present. Neither Pavlov nor more recent associative-learning theories could accurately explain or mathematically model this spontaneous recovery of an extinguished association. 

Teasing out the puzzle

Researchers have explored such mysteries through experiments with C. elegans. The one-millimeter roundworm only has about 1,000 cells and 300 of them are neurons. That simplicity provides scientists with a simple system to test how the animal learns. At the same time, C. elegans’ neural circuitry is just complicated enough to connect some of the insights gained from studying its behavior to more complex systems. 

Earlier experiments have established that C. elegans can be trained to prefer a cooler or warmer temperature by conditioning it at a certain temperature with food. In a typical experiment, the worms are placed in a petri dish with a gradient of temperatures but no food. Those trained to prefer a cooler temperature will move to the cooler side of the dish, while the worms trained to prefer a warmer temperature go to the warmer side. 

But what exactly do these result mean? Some believe that the worms crawl toward a particular temperature in expectation of food. Others argue that the worms simply become habituated to that temperature, so they prefer to hang out there even without a food reward. 

The puzzle could not be resolved due to a major limitation of many of these experiments — the lengthy amount of time it takes for a worm to traverse a nine-centimeter petri dish in search of the preferred temperature. 

Measuring how learning changes over time

Nemenman and Ryu sought to overcome this limitation. They wanted to develop a practical way to precisely measure the dynamics of learning, or how learning changes over time. 

Ryu’s lab used a microfluidic device to shrink the experimental model of nine-centimeter petri dishes into four-millimeter droplets. The researchers could rapidly run experiments on hundreds of worms, each worm encased within its individual droplet. 

“We could observe in real time how a worm moved across a linear gradient of temperatures,” Ryu says. “Instead of waiting for it to crawl for 30 minutes or an hour, we could much more quickly see which side of the droplet, the cold side or the warm side, that the worm preferred. And we could also follow how its preferences changed with time.” 

Their experiments confirmed that if a worm is trained to associate food with a cooler temperature it will move to the cooler side of the droplet. Over time, however, with no food present, this memory preference seemingly decays. 

“We found that suddenly the worms wanted to spend more time on the warm side of the droplet,” Ryu says. “That’s surprising because why would the worms develop a different preference and even avoidance of the temperature they had come to associate with food?” 

Eventually the worm begins moving back and forth between the cooler and warmer temperatures. The researchers hypothesized that the worm does not simply forget the positive memory of food associated with cooler temperatures but instead starts to negatively associate the cooler side with no food. That spurs it to head for the warmer side. Then as more time passes, it begins to form a negative association of no food with the warmer temperature, which combined with the residual positive association to the cold, makes it migrate back to the cooler one. 

“The worm is always learning, all the time,” Ryu explains. “There is an interplay between the drive of a positive association and a negative association that causes it to start oscillating between cold and warm.” 

'It's like when you lose your keys'

Nemenman’s team developed theoretical equations to describe the interactions over time between the two independent variables — the positive, or excitatory, association that drives a worm toward one temperature and the negative, or inhibitory, association that drives it away from that temperature. 

“The side that the worm gravitates toward depends on when exactly you take the measurements,” Nemenman explains. “It’s like when you lose your keys you may check the desk where you usually keep them first. If you don’t see them there right away, you run around different places looking for them. If you still don’t find them, you go back to the original desk figuring you just didn’t look hard enough.” 

The researchers repeated the experiments under different conditions. They trained the worms at different starting temperatures and starved them for different durations before testing their temperature preference, and the worms’ behaviors were correctly predicted by the equations. 

They also tested their hypothesis by genetically modifying the worms, knocking out the insulin-like signaling pathway known to serve as a negative association pathway. 

“We perturbed the biology in specific ways and when we ran the experiments, the worm’s behavior changed as predicted by our theoretical model,” Nemenman says. “That gives us more confidence that the model reflects the underlying biology of learning, at least in C. elegans.” 

The researchers hope that others will test their model in studies of larger animals across species. 

“Our model provides an alternative quantitative model of learning that is multi-dimensional,” Ryu says. “It explains results that are difficult, or in some cases impossible, for other theories of classical conditioning to explain.” 

Related:

Physicists develop theoretical model for neural activity of mouse brain

Machine learning used to understand and predict dynamics of worm behavior

Hidden 'super spreaders' spur dengue fever transmission

A NASA satellite image shows Iquitos, Peru, nestled in the Amazon Basin, on the banks of the Amazon River and surrounded by smaller rivers, lakes and lagoons.

By Carol Clark

For mosquito-borne diseases such as dengue fever, the abundance of the insects in places where people gather has long served as the main barometer for infection risk. A new study, however, suggests that the number of “hidden” infections tied to a place, or cases of infected people who show no symptoms, is the key indicator for dengue risk. 

PNAS Nexus published the research led by scientists at Emory University, which drew from six years of data collected in the Amazonian city of Iquitos, Peru. 

The results found that 8% of human activity spaces in the study accounted for more than half of infections during a dengue outbreak. And these “super spreader” spaces were associated with a predominance of asymptomatic cases, or 74% of all infections. 

“Our findings show that any public health intervention that focuses on responding to symptomatic cases of dengue is going to fail to control an outbreak,” says Gonzalo Vazquez-Prokopec, first author of the study and an Emory associate professor of environmental sciences. “Symptomatic cases represent only the tip of the iceberg.” 

Co-authors of the research include Uriel Kitron, Emory professor of environmental sciences; Lance Waller, professor of biostatistics and bioinformatics at Emory’s Rollins School of Public Health; and scientists from University of California-Davis, Tulane University, San Diego State University, University of Notre Dame, North Carolina State University and the U.S. Naval Medical Research Unit in Lima, Peru. 

'What matters is where you went'

Dengue fever is caused by a virus transmitted by the bite of a female Aedes aegypti mosquito. When the insect takes a blood meal from a human infected with dengue, the virus begins replicating within the mosquito. The virus may then spread to another person that the mosquito bites days later. 

This species of mosquito feeds exclusively on human blood, has a limited flight range of about 100 meters and thrives in sprawling urban areas of the tropics and subtropics. Its preferred habitat is inside homes, where it rests on the backs of furniture and at the bases of walls. Even the little bit of water held by an upturned bottle cap can serve as a nursery for its larvae. 

Vazquez-Prokopec is pioneering new mosquito-borne disease interventions, including tapping spatiotemporal data to track, predict and control outbreaks of pathogens transmitted by Aedes aegypti. The mosquito spreads the Zika, chikungunya and yellow fever viruses in addition to dengue. 

Around 500,000 cases of dengue occur annually around the world, according to the World Health Organization. The disease is caused by four distinct but closely related serotypes of the dengue virus. Infected people may have some immunity that prevents them from experiencing any noticeable effects while others may be severely debilitated for a week or more by symptoms such as extreme aches and pains, vomiting and rashes. Dengue hemorrhagic fever, the most severe form of the disease, causes an estimated 25,000 deaths annually worldwide. 

Iquitos, a city of nearly 500,000 people on the edge of the Amazon rainforest in Peru, is a dengue hotspot. For more than a decade, Vazquez-Prokopec and colleagues have mapped patterns of human mobility and dengue spread in Iquitos. 

“For diseases that are directly spread from one person to another, like COVID-19, what matters is who you were near,” he says. “But in the case of dengue, what matters most is where you went.” 

Tracking hidden cases

For the current study, the researchers wanted to determine the role of asymptomatic cases. People without symptoms may continue to go about their daily routines, unknowingly infecting any mosquitoes that bite them, which can then later spread the virus to more people. 

The study involved 4,600 people in two different neighborhoods. They were surveyed three times a week about their mobility. This data was used to map “activity spaces,” such as residences, churches and schools. 

The study participants were also regularly surveilled to determine if they experienced any dengue symptoms. Blood analyses confirmed a total of 257 symptomatic cases of dengue during the six-year study period. That led to investigations of other participants whose activity spaces overlapped with the symptomatic cases. More than 2,000 of these location-based contacts were confirmed by blood tests to have dengue infections and more than half of them reported not having any noticeable symptoms. 

A cascade of circumstances

The results pinpointed the role of asymptomatic “super spreaders” in a dengue outbreak. A small number of the activity spaces, or 8%, were linked to more than half of the infections and most of the cases associated with those places were asymptomatic. 

The comprehensive, one-of-a-kind study broke down the virus infections by serotype and measured the amount of mosquitoes in the activity spaces. 

“We found that the mosquito numbers in a location alone is not a predictor of the risk of infection,” Vazquez-Prokopec says. 

Instead, risk prediction for a location requires a cascade of circumstances: a high number of asymptomatic cases frequenting the location combined with high levels of mosquitos and high numbers of people who are not immune to the particular serotype of dengue virus that is circulating. 

“That’s the complicated nature of this virus,” Vazquez-Prokopec says. “We have underestimated the role of asymptomatic cases in spreading dengue.” 

Generally, about 50 to 70% of dengue cases are asymptomatic, making detection by public health officials impractical, and the current study reveals that asymptomatic cases are tied to a third of transmission. 

“The lesson is that we need to focus on prevention of dengue outbreaks,” Vazquez-Prokopec says. “The interventions for dengue for decades have been reactive. Simply reacting by closing a net around reported cases of the disease, however, will fail to contain an outbreak because that’s missing the super spreaders.” 

The study was funded by the U.S. National Institute of Allergy and Infectious Diseases, Bill and Melinda Gates Foundation, University of Notre Dame, Defense Threat Reduction Agency, Military Infectious Disease Research Program and the Armed Forces Health Surveillance Branch Global Emerging Infections Systems research program. 

Related:

Tapping big data to target a tiny predator 

Mapping dengue hot spots pinpoints risks for Zika and chikungunya 

Mutant mosquitoes make insecticide-resistance monitoring key to control Zika

Atlanta Science Festival expands your horizons

Rae Wynn-Grant admires a bear cub after tagging it. "I hope that I can play a small role in helping people see that science is a space where anyone can find belonging," she says.

"Science has quite literally taken me around the world," says Rae Wynn-Grant, an Emory alumna and wildlife biologist whose field research has spanned six continents.

"But you don't have to physically travel to be a great scientist," she adds. "I want people to know that there are many different ways that science can expand your horizons." 

Wynn-Grant returns to Atlanta as a featured speaker to launch this year's Atlanta Science Festival, set for March 10-25. The festival is bigger and more expansive than ever with more than 150 events and an overarching theme: Where will science take you?

Read more about the festival here.

Study shows long-term trend of undocumented Mexican immigrants most at risk for deportation from U.S.

No matter the U.S. political climate, young, single and less educated men seemed to be at higher risk for deportation than other undocumented Mexican immigrants from 2001 to 2019, a study led by Emory University finds. 

The Proceedings of the National Academy of Sciences (PNAS) published the study analyzing deportation and voluntary return migration data encompassing the administrations of U.S. Presidents George W. Bush, Barack Obama and Donald Trump. 

“Even through the Trump administration’s anti-immigrant rhetoric advocated deporting all undocumented immigrants, particularly from Mexico, the characteristics of Mexican immigrants deported during the Trump years were not dramatically different from previous administrations,” says Heeju Sohn, Emory assistant professor of sociology and lead author of the study. 

Co-authors include Anne Pebley and Amanda Landrian Gonzalez from the University of California Los Angeles and Noreen Goldman of Princeton University. 

The researchers examined trends in socio-demographic characteristics of undocumented Mexican immigrants deported by the U.S. along with those who chose to return to Mexico. 

While the study does not predict or offer any absolute probabilities, it provides insight into relative potential risks. 

On average, each administration annually deported about 893,000 people with the majority of them Mexican citizens. 

“Despite each administration’s differing approach and rhetoric, who was actually being deported or deciding to leave didn’t change all that much,” Sohn said. “Just because an undocumented person voluntary leaves the U.S. doesn’t always mean they felt they had a choice in that decision either.” 

Fewer immigrants were deported annually during the Trump administration than under Obama or Bush who had the highest number of deportations. During Obama’s first term, there was an increase in deportation of Mexican immigrants with criminal convictions but that percentage decreased in the last two years of his presidency. 

While Trump’s administration prioritized all undocumented immigrants for deportation, the result shows deportation focused more on young adults and those with less education, groups which already face higher deportation risks. 

"Policy makers and the public need to understand the consequences of the immigration policies that are implemented – whether they work or not,” says Pebley, a UCLA California Center for Population Research faculty fellow. “While the Trump administration's anti-immigrant rhetoric and policies had many negative effects on immigrants and Americans, they did not do what they were apparently intended to in terms of deporting a larger and more diverse group of undocumented immigrants.” 

The Trump administration’s anti-immigrant rhetoric and heightened enforcement didn’t appear to motivate a more diverse group of undocumented immigrants to leave voluntarily. Rather, voluntary return migration to Mexico was a trend that began early in the Obama administration after the great recession of 2007-2009, according to the study. 

“People who are leaving or being deported do not exist in a vacuum,” Sohn says. “You can’t isolate them separately from the social and family connections they have interwoven in U.S. society. So, what happens to undocumented people that society has neglected has a direct effect on the well-being of U.S. citizens. We have a duty to not discriminate and there is a need for additional research.” 

The experiences of undocumented children living in the U.S. is a blind spot in national data; the youngest age group in this study is 18 to 31. 

“Moving across countries is a disruptive life event,” Sohn says. “This is an age group where people take major steps as adults—finding a partner, having children or establishing a career. This can have reverberating consequences for the rest of their lives.” 

For the study, Sohn and the other researchers combined deportees’ and voluntary returnees’ data from both sides of the border—the Migration Survey on the Borders of Mexico-North (EMIF-N) and U.S. Current Population Survey’s Annual Social and Economic Supplement (ASEC). It’s the first time these two major sets of data were combined for research purposes and studied in a novel way. 

“It was critical that we understood the nuances of the data and sampling strategy. We took a lot of timand effort making sure our method accounted for the differences,” Sohn says. 

“This is part of a bigger desire to make sure the lives of underrepresented groups have adequate representation,” she adds. “A lot of the research in social sciences are based on large data sets that don’t put much focus on the smaller groups or ones that are harder to measure. I hope getting this important topic published will get visibility to a wider audience.” 

Funding for the story was provided by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (ROOHDO96322).