Innate ability to vocalize: Deaf or not, courting male mice make same sounds

Scientists have long thought mice might be a model for how humans learn to vocalize. But new research led by scientists at Washington State University Vancouver has found that, unlike humans and songbirds, mice do not learn to vocalize.

The results, published in the Journal of Neuroscience, point the way to a more finely focused, genetic tool for teasing out the mysteries of speech and its disorders.

To see if mice learn to vocalize, WSU neurophysiologist Christine Portfors destroyed the ear hair cells in more than a dozen newborn male mice. The cells convert sound waves into electrical signals processed by the brain, making hearing possible.

The deaf mice were then raised with hearing mice in a normal social environment.

Portfors and her fellow researchers, including WSU graduate student Elena Mahrt, used males because they are particularly exuberant vocalizers in the presence of females.

"We can elicit vocalization behavior in males really easily by just putting them with a female,” Portfors said. "They vocalize like crazy.”

And it turned out that it didn’t matter if the mouse was deaf or not. The researchers catalogued essentially the same suite of ultrasonic sounds from both the deaf and hearing mice. “It means that they don’t need to hear to be able to produce their sounds, their vocalizations,” Portfors said. “Basically, they don’t need to hear themselves. They don’t need auditory feedback. They don’t need to learn.”

The finding means mice are out as a model to study vocal learning. However, scientists can now focus on the mouse to learn the genetic mechanism behind communication disorders.

"If you don’t have learning as a variable, you can look at the genetic control of these things,” Portfors said. "You can look at the genetic control of the output of the signal. It’s not messed up by an animal that’s been in a particular learning situation.”

(Image: Fotolia)

Brain Size Didn’t Drive Evolution, Research Suggests

Brain organization, not overall size, may be the key evolutionary difference between primate brains, and the key to what gives humans their smarts, new research suggests.

In the study, researchers looked at 17 species that span 40 million years of evolutionary time, finding changes in the relative size of specific brain regions, rather than changes in brain size, accounted for three-quarters of brain evolution over that time. The study, published today (March 26) in the Proceedings of the Royal Society B, also revealed that massive increases in the brain’s prefrontal cortex played a critical role in great ape evolution.

"For the first time, we can really identify what is so special about great ape brain organization," said study co-author Jeroen Smaers, an evolutionary biologist at the University College London.

Is bigger better?

Traditionally, scientists have thought humans’ superior intelligence derived mostly from the fact that our brains are three times bigger than our nearest living relatives, chimpanzees.

But bigger isn’t always better. Bigger brains take much more energy to power, so scientists have hypothesized that brain reorganization could be a smarter strategy to evolve mental abilities.

To see how brain organization evolved throughout primates, Smaers and his colleague Christophe Soligo analyzed post-mortem slices of brains from 17 different primates, then mapped changes in brain size onto an evolutionary tree.

Over evolutionary time, several key brain regions increased in size relative to other regions. Great apes (especially humans) saw a rise in white matter in the prefrontal cortex, which contributes to social cognition, moral judgments, introspection and goal-directed planning.

"The prefrontal cortex is a little bit like the CEO of the brain," Smaers told LiveScience. "It takes information from other brain areas and it synthesizes them."

When great apes diverged from old-world monkeys about 20 million years ago, brain regions tied to motor planning also increased in relative size. That could have helped them orchestrate the complex movements needed to manipulate tools — possibly to get at different food sources, Smaers said.

Gibbons and howler monkeys showed a different pattern. Even though their bodies and their brains got smaller over time, the hippocampus, which plays a role in spatial tasks, tended to increase in size in relation to the rest of the brain. That may have allowed these monkeys to be spatially adept and inhabit a more diverse range of environments.

Prefrontal cortex

The study shows that specific parts of the brain can selectively scale up to meet the demands of new environments, said Chet Sherwood, an anthropologist at George Washington University, who was not involved in the study.

The finding also drives home the importance of the prefrontal cortex, he said.

"It’s very suggestive that connectivity of prefrontal cortex has been a particularly strong driving force in ape and human brains," Sherwood told LiveScience.

New urgency in battle against ‘bound legs’ disease

The harm done by konzo – a disease overshadowed by the war and drought it tends to accompany – goes beyond its devastating physical effects to impair children’s memory, problem solving and other cognitive functions.

Even children without physical symptoms of konzo appear to lose cognitive ability when exposed to the toxin that causes the disease, researchers report in the journal Pediatrics.

“That’s what’s especially alarming,” said lead author Michael Boivin, a Michigan State University associate professor of psychiatry and of neurology and ophthalmology. “We found subtle effects that haven’t been picked up before. These kids aren’t out of the woods, even if they don’t have the disease.”

Konzo means “bound legs” in the African Yaka language, a reference to how its victims walk with feet bent inward after the disease strips away motor control in their lower limbs. Its onset is rapid, and the damage is permanent.

People contract konzo by consuming poorly processed bitter cassava, a drought-resistant staple food in much of sub-Saharan Africa. Typically, the plant’s tuber is soaked for a few days, then dried in the sun and ground into flour – a process that degrades naturally occurring cyanide.

“As long as they do that, the food’s pretty safe,” said Boivin, who began studying konzo in 1990 as a Fulbright researcher in the Democratic Republic of Congo. “But in times of war, famine, displacement and hardship, people take shortcuts. If they’re subsisting on poorly processed cassava and they don’t have other sources of protein, it can cause permanent damage to the nervous system.

“Konzo doesn’t make many headlines because it usually follows other geopolitical aspects of human suffering,” he added. “Still, there are potentially tens of millions of kids at risk throughout central and western Africa. The public health scope is huge.”

To find out if the disease affects cognitive function, Boivin and colleagues from Oregon Health and Science University turned to the war-torn Congo. They randomly selected 123 children with konzo and 87 neighboring children who showed no signs of the disease but whose blood and urine samples indicated elevated levels of the toxin.

Using cognitive tests, the researchers found that children with konzo had a much harder time using working memory to solve problems and organize visual and spatial information.

They also found that konzo and non-konzo children from the outbreak area showed poor working memory and impaired fine-motor skills when compared to a reference group of children from a part of the region unaffected by the disease.

Konzo’s subtler impacts might seem minor compared to its striking physical symptoms, but Boivin noted that the cognitive damage is similar to that caused by chronic low-grade exposures to other toxic substances such as lead.

Scientists eventually may be able to prevent such damage by creating nontoxic cassava varieties and introducing other resilient crops to affected regions, Boivin said. Meanwhile, public health education programs are under way to help stop outbreaks.

“For now,” he said, “if we could just avoid the worst of it – the full-blown konzo disease that has such devastating effects for children and families – that’s a good start.”

Research Provides Clues to Alcohol Addiction Vulnerability

A Wake Forest Baptist Medical Center team studying alcohol addiction has new research that might shed light on why some drinkers are more susceptible to addiction than others.

Jeff Weiner, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist, and colleagues used an animal model to look at the early stages of the addiction process and focused on how individual animals responded to alcohol. Their findings may lead not only to a better understanding of addiction, but to the development of better drugs to treat the disease as well, Weiner said.

"We know that some people are much more vulnerable to alcoholism than others, just like some people have a vulnerability to cancer or heart disease," Weiner said. "We don’t have a good understanding of what causes this vulnerability, and that’s a big question. But if we can figure it out, we may be able to better identify people at risk, as well as gain important clues to help develop better drugs to treat the disease."

The findings are published in the March 13 issue of the Journal of Neuroscience. Weiner, who directs the Translational Studies on Early-Life Stress and Vulnerability to Alcohol Addiction project at Wake Forest Baptist, said the study protocol was developed by the first author of the paper, Karina Abrahao, a graduate student visiting from the collaborative lab of Sougza-Formigoni, Ph.D, of the Department of Psychobiology at the Federal University of Sao Paulo, Brazil.

Weiner said the study model focused on how individual animals responded to alcohol. Typically, when a drug like alcohol is given to a mouse every day, the way the animals respond increases - they become more stimulated and run around more. “In high doses, alcohol is a depressant, but in low doses, it can have a mellowing effect that results in greater activity,” he said. “Those low dose effects tend to increase over time and this increase in activity in response to repeated alcohol exposure is called locomotor sensitization.”

Prior studies with other drugs, such as cocaine and amphetamine, have suggested that animals that show the greatest increases in locomotor sensitization are also the animals most likely to seek out or consume these drugs. However, the relationship between locomotor sensitization and vulnerability to high levels of alcohol drinking is not as well established, Weiner said.

Usually when researchers are studying a drug, they give it to one test group while the other group gets a control solution, and then they look for behavioral differences between the two, Weiner said. But in this study, the researchers focused on individual differences in how each animal responded to the alcohol. A control group received a saline injection while another was injected with the same amount of alcohol every day for three weeks. Weiner said they used mice bred to be genetically variable like humans to make the research more relevant.

"We found large variations in the development of locomotor sensitization to alcohol in these mice, with some showing robust sensitization and others showing no more of a change in locomotor activity than control mice given daily saline injections," Weiner said. "Surprisingly, when all of the alcohol-exposed mice were given an opportunity to voluntarily drink alcohol, those that had developed sensitization drank more than those that did not. In fact, the alcohol-treated mice that failed to develop sensitization drank no more alcohol than the saline-treated control group."

The authors also conducted a series of neurobiological studies and discovered that mice that showed robust locomotor sensitization had deficits in a form of brain neuroplasticity - how experiences reorganize neural pathways in the brain - that has been linked with cocaine addiction in other animal models.

"We found that this loss of the ability of brain cells to change the way that they communicate with each other only occurred in the animals that showed the behavioral response to alcohol," he said. "What this suggests for the first time in the alcohol addiction field is that this particular deficit may represent an important brain correlate of vulnerability to alcoholism. It’s a testable hypothesis. That’s why I think it’s an important finding."

Hunger-spiking neurons could help control autoimmune diseases

Neurons that control hunger in the central nervous system also regulate immune cell functions, implicating eating behavior as a defense against infections and autoimmune disease development, Yale School of Medicine researchers have found in a new study published in the Proceedings of the National Academies of Sciences (PNAS).

Autoimmune diseases have been on a steady rise in the United States. These illnesses develop when the body’s immune system turns on itself and begins attacking its own tissues. The interactions between different kinds of T cells are at the heart of fighting infections, but they have also been linked to autoimmune disorders.

“We’ve found that if appetite-promoting AgRP neurons are chronically suppressed, leading to decreased appetite and a leaner body weight, T cells are more likely to promote inflammation-like processes enabling autoimmune responses that could lead to diseases like multiple sclerosis,” said lead author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine.

“If we can control this mechanism by adjusting eating behavior and the kinds of food consumed, it could lead to new avenues for treating autoimmune diseases,” he added.

Horvath and his research team conducted their study in two sets of transgenic mice. In one set, they knocked out Sirt1, a signaling molecule that controls the hunger-promoting neuron AgRP in the hypothalamus. These Sirt1-deficient mice had decreased regulatory T cell function and enhanced effector T cell activity, leading to their increased vulnerability in an animal model of multiple sclerosis.

“This study highlights the important regulatory role of the neurons that control appetite in peripheral immune functions,” said Horvath. “AgRP neurons represent an important site of action for the body’s immune responses.”

The team’s data support the idea that achieving weight loss through the use of drugs that promote a feeling of fullness “could have unwanted effects on the spread of autoimmune disorders,” he notes.

Brain scans predict which criminals are more likely to reoffend

In a twist that evokes the dystopian science fiction of writer Philip K. Dick, neuroscientists have found a way to predict whether convicted felons are likely to commit crimes again from looking at their brain scans. Convicts showing low activity in a brain region associated with decision-making and action are more likely to be arrested again, and sooner.

Kent Kiehl, a neuroscientist at the non-profit Mind Research Network in Albuquerque, New Mexico, and his collaborators studied a group of 96 male prisoners just before their release. The researchers used functional magnetic resonance imaging (fMRI) to scan the prisoners’ brains during computer tasks in which subjects had to make quick decisions and inhibit impulsive reactions.

The scans focused on activity in a section of the anterior cingulate cortex (ACC), a small region in the front of the brain involved in motor control and executive functioning. The researchers then followed the ex-convicts for four years to see how they fared.

Among the subjects of the study, men who had lower ACC activity during the quick-decision tasks were more likely to be arrested again after getting out of prison, even after the researchers accounted for other risk factors such as age, drug and alcohol abuse and psychopathic traits. Men who were in the lower half of the ACC activity ranking had a 2.6-fold higher rate of rearrest for all crimes and a 4.3-fold higher rate for nonviolent crimes. The results are published in the Proceedings of the National Academy of Sciences.

There is growing interest in using neuroimaging to predict specific behaviour, says Tor Wager, a neuroscientist at the University of Colorado in Boulder. He says that studies such as this one, which tie brain imaging to concrete clinical outcomes, “provide a new and so far very promising way” to find patterns of brain activity that have broader implications for society.

But the authors themselves stress that much more work is needed to prove that the technique is reliable and consistent, and that it is likely to flag only the truly high-risk felons and leave the low-risk ones alone. “This isn’t ready for prime time,” says Kiehl.

Wager adds that the part of the ACC examined in this study “is one of the most frequently activated areas in the human brain across all kinds of tasks and psychological states”. Low ACC activity could have a variety of causes — impulsivity, caffeine use, vascular health, low motivation or better neural efficiency — and not all of these are necessarily related to criminal behaviour.

Crime prediction was the subject of Dick’s 1956 short story “The Minority Report” (adapted for the silver screen by Steven Spielberg in 2002), which highlighted the thorny ethics of arresting people for crimes they had yet to commit.

Brain scans are of course a far cry from the clairvoyants featured in that science-fiction story. But even if the science turns out to be reliable, the legal and social implications remain to be explored, the authors warn. Perhaps the most appropriate use for neurobiological markers would be for helping to make low-stakes decisions, such as which rehabilitation treatment to assign a prisoner, rather than high-stakes ones such as sentencing or releasing on parole.

“A treatment of [these clinical neuroimaging studies] that is either too glibly enthusiastic or over-critical,” Wager says, “will be damaging for this emerging science in the long run.”

New mechanism for long-term memory formation discovered

UC Irvine neurobiologists have found a novel molecular mechanism that helps trigger the formation of long-term memory. The researchers believe the discovery of this mechanism adds another piece to the puzzle in the ongoing effort to uncover the mysteries of memory and, potentially, certain intellectual disabilities.

In a study led by Marcelo Wood of UC Irvine’s Center for the Neurobiology of Learning & Memory, the team investigated the role of this mechanism – a gene designated Baf53b – in long-term memory formation. Baf53b is one of several proteins making up a molecular complex called nBAF.

Mutations in the proteins of the nBAF complex have been linked to several intellectual disorders, including Coffin-Siris syndrome, Nicolaides-Baraitser syndrome and sporadic autism. One of the key questions the researchers addressed is how mutations in components of the nBAF complex lead to cognitive impairments.

In their study, Wood and his colleagues used mice bred with mutations in Baf53b. While this genetic modification did not affect the mice’s ability to learn, it did notably inhibit long-term memories from forming and severely impaired synaptic function.

“These findings present a whole new way to look at how long-term memories form,” said Wood, associate professor of neurobiology & behavior. “They also provide a mechanism by which mutations in the proteins of the nBAF complex may underlie the development of intellectual disability disorders characterized by significant cognitive impairments.”

How does this mechanism regulate gene expression required for long-term memory formation? Most genes are tightly packaged by a chromatin structure – chromatin being what compacts DNA so that it fits inside the nucleus of a cell. That compaction mechanism represses gene expression. Baf53b, and the nBAF complex, physically open the chromatin structure so specific genes required for long-term memory formation are turned on. The mutated forms of Baf53b did not allow for this necessary gene expression.

“The results from this study reveal a powerful new mechanism that increases our understanding of how genes are regulated for memory formation,” Wood said. “Our next step is to identify the key genes the nBAF complex regulates. With that information, we can begin to understand what can go wrong in intellectual disability disorders, which paves a path toward possible therapeutics.”

Findings appear online today in Nature Neuroscience.

Developing Our Sense of Smell

When our noses pick up a scent, whether the aroma of a sweet rose or the sweat of a stranger at the gym, two types of sensory neurons are at work in sensing that odor or pheromone. These sensory neurons are particularly interesting because they are the only neurons in our bodies that regenerate throughout adult life—as some of our olfactory neurons die, they are soon replaced by newborns. Just where those neurons come from in the first place has long perplexed developmental biologists.

Previous hypotheses about the origin of these olfactory nerve cells have given credit to embryonic cells that develop into skin or the central nervous system, where ear and eye sensory neurons, respectively, are thought to originate. But biologists at the California Institute of Technology (Caltech) have now found that neural-crest stem cells—multipotent, migratory cells unique to vertebrates that give rise to many structures in the body such as facial bones and smooth muscle—also play a key role in building olfactory sensory neurons in the nose.

"Olfactory neurons have long been thought to be solely derived from a thickened portion of the ectoderm; our results directly refute that concept," says Marianne Bronner, the Albert Billings Ruddock Professor of Biology at Caltech and corresponding author of a paper published in the journal eLIFE on March 19 that outlines the findings.

The two main types of sensory neurons in the olfactory system are ciliated neurons, which detect volatile scents, and microvillous neurons, which usually sense pheromones. Both of these types are found in the tissue lining the inside of the nasal cavity and transmit sensory information to the central nervous system for processing.

In the new study, the researchers showed that during embryonic development, neural-crest stem cells differentiate into the microvillous neurons, which had long been assumed to arise from the same source as the odor-sensing ciliated neurons. Moreover, they demonstrated that different factors are necessary for the development of these two types of neurons. By eliminating a gene called Sox10, they were able to show that formation of microvillous neurons is blocked whereas ciliated neurons are unaffected.

They made this discovery by studying the development of the olfactory system in zebrafish—a useful model organism for developmental biology studies due to the optical clarity of the free-swimming embryo. Understanding the origins of olfactory neurons and the process of neuron formation is important for developing therapeutic applications for conditions like anosmia, or the inability to smell, says Bronner.

"A key question in developmental biology—the extent of neural-crest stem cell contribution to the olfactory system—has been addressed in our paper by multiple lines of experimentation," says Ankur Saxena, a postdoctoral scholar in Bronner’s laboratory and lead author of the study. "Olfactory neurons are unique in their renewal capacity across species, so by learning how they form, we may gain insights into how neurons in general can be induced to differentiate or regenerate. That knowledge, in turn, may provide new avenues for pursuing treatment of neurological disorders or injury in humans."

Next, the researchers will examine what other genes, in addition to Sox10, play a role in the process by which neural-crest stem cells differentiate into microvillous neurons. They also plan to look at whether or not neural-crest cells give rise to new microvillous neurons during olfactory regeneration that happens after the embryonic stage of development.