Posts Tagged ‘learning’

The majority of the cells in the brain are no neurons, but Glia (from “glue”) cells, that support the structure and function of the brain. Astrocytes (“start cells”) are star-shaped glial cells providing many supportive functions for the neurons surrounding them, such as the provision of nutrients and the regulation of their chemical environment. Newer studies showed that astrocytes also monitor and modulate neuronal activity. For example, these studies have shown that astrocytes are necessary for the ability of neurons to change the strength of the connections between them, the process underlying learning and memory, and indeed astrocytes are also necessary for normal cognitive function. However, it is still unknown whether astrocytic activity is only necessary, or is it may also be sufficient to induce synaptic potentiation and enhance cognitive performance.

In a new study published in Cell, two graduate students, Adar Adamsky and Adi Kol, from Inbal Goshen’s lab, employed chemogenetic and optogenetic tools that allow specific activation of astrocytes in behaving mice, to explore their role in synaptic activity and memory performance. They found that astrocytic activation in the hippocampus, a brain region that plays an important role in memory acquisition and consolidation, potentiated the synaptic connections in this region, measured in brain slices. Moreover, in the intact brain, astrocytic activation enhanced hippocampal neuronal activity in a task-dependent way: i.e. only during when it was combined with memory acquisition, but not when mice were at their home cage with no meaningful stimuli. The ability of astrocytes to increase neuronal activity during memory acquisition had a significant effect on cognitive function: Specifically, astrocytic activation during learning resulted in enhanced memory in two memory tests. In contrast, direct neuronal activation in the hippocampus induced a non-selective increase in activity (during learning or in the home cage), and thus resulted in drastic memory impairment.

The results suggest that the memory enhancement induced by astrocytic activation during learning is not simply a result of a general increase in hippocampal neuronal activity. Rather, the astrocytes, which sense and respond to changes in the surrounding neuronal activity, can detect and specifically enhance only the neuronal activity involved in learning, without affecting the general activity. This may explain why general astrocytic activation improves memory performance, whereas a similar activation of neurons impairs it.

Memory is not a binary process (remember/don’t remember); the strength of a memory can vary greatly, either for the same memory or between different memories. Here, we show that activating astrocytes in mice with intact cognition improves their memory performance. This finding has important clinical implications for cognitive augmentation treatments. Furthermore, the ability of astrocytes to strengthen neuronal communication and improve memory performance supports the claim that astrocytes are able to take an active part in the neuronal processes underlying cognitive function. This perspective expands the definition of the role of astrocytes, from passive support cells to active cells that can modulate neural activity and thus shape behavior.



by Nicolas Scherger

Dr. Thomas Hainmüller and Prof. Dr. Marlene Bartos of the Institute of Physiology of the University of Freiburg have established a new model to explain how the brain stores memories of tangible events. The model is based on an experiment that involved mice seeking a place where they received rewards in a virtual environment. The scientific journal “Nature” has published the study.

In the world of the mouse’s video game, the walls that depict a corridor four meters long are made up of green and blue patterned blocks. The floor is marked with turquoise dots. A short distance away, there’s a brown disc on the floor that looks like a cookie. That’s the symbol for the reward location. The mouse heads for it, gets there, and the symbol disappears. The next cookie promptly appears a bit further down the corridor. The mouse is surrounded by monitors and is standing on a styrofoam ball that is floating on compressed air and turns beneath the mouse when it runs. The ball makes it possible to transfer of the mouse’s movements to the virtual environment. If the mouse reaches the reward symbol, a straw is used to give it a drop of soy milk and stimulate it to form memories of its experiences in the virtual world. The mouse learns when, and at which location, it will receive a reward. It also learns how to locate itself and discriminate between different corridors in the video game.

Viewing the brain with a special microscope

“As the mouse is getting to know its environment, we use a special microscope to look from the outside into its brain and we record the activities of its nerve cells on video,” explains Thomas Hainmüller, a physician and doctoral candidate in the MD/PhD program of the Spemann Graduate School of Biology and Medicine (SGBM) of the University of Freiburg. He says that works because, in reality, the head of the mouse remains relatively still under the microscope as it runs through the virtual world of the video game. On the recordings, the mice’s genetically-manipulated nerve cells flash as soon as they become active. Hainmüller and Marlene Bartos, a Professor of Systemic and Cellular Neurobiology are using this method to investigate how memories are sorted and retrieved. “We repeatedly place the mouse in the virtual world on consecutive days,” says Hainmüller. “In that way, we can observe and compare the activity of the nerve cells in different stages of memory formation,” he explains.

Nerve cells encode places

The region of the brain called the hippocampus plays a decisive role in the formation of memory episodes – or memories of tangible experiences. Hainmüller and Bartos published that the nerve cells in the hippocampus create a map of the virtual world in which single neurons code for actual places in the video game. Earlier studies done at the Freiburg University Medical Center showed that nerve cells in the human hippocampus code video games in the same way. The cells become activated and flash when the mouse is at the respective place, otherwise they remain dark. “To our surprise, we found very different maps inside the hippocampus,” reports Hainmüller. In part, they provide an approximate overview of the position of the mouse in the corridor, yet they also consider time and context factors, and above all, information about in which of the corridors the mouse is located. The maps are also updated during the days of the experiment and as a result can be recognized as a learning process.

Better understanding of memory formation

The research team summarizes, saying that their observations provide a model that explains how activity of the nerve cells in the hippocampus can map the space, time and and context of memory episodes. The findings allow for better understanding of the biological processes that effect the formation of memory in the brain. Hainmüller says, “In the long term, we would like to use our results to contribute to the development of treatments to help people with neurological and psychiatric illnesses.”

Original publication
Thomas Hainmüller and Marlene Bartos (2018): Parallel emergence of stable and dynamic memory engrams in the hippocampus. In: Nature. doi: 10.1038/s41586-018-0191-2

By Ruth Williams

The sun’s ultraviolet (UV) radiation is a major cause of skin cancer, but it offers some health benefits too, such as boosting production of essential vitamin D and improving mood. A recent report in Cell adds enhanced learning and memory to UV’s unexpected benefits.

Researchers have discovered that, in mice, exposure to UV light activates a molecular pathway that increases production of the brain chemical glutamate, heightening the animals’ ability to learn and remember.

“The subject is of strong interest, because it provides additional support for the recently proposed theory of ultraviolet light’s regulation of the brain and central neuroendocrine system,” dermatologist Andrzej Slominski of the University of Alabama who was not involved in the research writes in an email to The Scientist.

“It’s an interesting and timely paper investigating the skin-brain connection,” notes skin scientist Martin Steinhoff of University College Dublin’s Center for Biomedical Engineering who also did not participate in the research. “The authors make an interesting observation linking moderate UV exposure to . . . [production of] the molecule urocanic acid. They hypothesize that this molecule enters the brain, activates glutaminergic neurons through glutamate release, and that memory and learning are increased.”

While the work is “fascinating, very meticulous, and extremely detailed,” says dermatologist David Fisher of Massachusetts General Hospital and Harvard Medical School, “it does not imply that UV is actually good for you. . . . Across the board, for humanity, UV really is dangerous.”

Wei Xiong of the University of Science and Technology of China who led the research did not set out to investigate the effects of UV light on the brain or the skin-brain connection. He stumbled upon his initial finding “almost accidentally,” he explains in an email to The Scientist. Xiong and his colleagues were using a mass spectrometry technique they had recently developed for analyzing the molecular contents of single neurons, when their results revealed the unexpected presence of urocanic acid—a little-known molecule produced in the skin in response to UV light.

“It was a surprise because we checked through all the literature and found no reports of the existence of this small molecule in the central nervous system,” writes Xiong.

With little information to go on, Xiong and his colleagues decided to see whether UV light could also boost levels of urocanic acid in the brain. They exposed shaved mice to a low-dose of UVB—responsible for sunburn in humans—for 2 hours, then performed mass spectrometry on the animals’ individual brain cells. Sure enough, levels of urocanic acid increased in neurons of the animals exposed to the light, but not in those of control animals.

Urocanic acid can absorb UV rays and, as a result, may be able to protect skin against the sun’s harmful effects. But in the liver and other peripheral tissues, the acid is also known to be an intermediate molecule generated in the metabolic pathway that converts histidine to glutamate. Given glutamate’s role in the brain as an excitatory neurotransmitter, Xiong and his colleagues were interested to test whether the observed UV-dependent increase in urocanic acid in neurons might be coupled with increased glutamate production. It was.

Next, the team showed that UV light enhanced electrical transmission between glutaminergic neurons in brain slices taken from animals exposed to UV, but not in those from control animals. This UV-induced effect was prevented when the researchers inhibited activity of the enzyme urocanase, which converts urocanic acid to glutamate, indicating that the acid was indeed the mediator of the UV-induced boost in glutaminergic activity.

Lastly, the team showed that mice exposed to UV performed better in motor learning and recognition memory tasks than their unexposed counterparts. And, as before, treating the animals with a urocanase inhibitor prevented the UV-induced improvements in learning and memory. Administering urocanic acid directly to animals not exposed to ultraviolet light also spurred similar learning and memory improvements to those achieved with UV exposure.

Whether the results obtained in mice, which are nocturnal and rarely see the sun, will hold true in humans is yet to be determined. But, Fisher says, if the results do hold, the finding that urocanic acid alone can enhance learning and memory might suggest “a way to utilize this information to benefit people without exposing them to the damaging effects of UV.”

H. Zhu et al., “Moderate UV exposure enhances learning and memory by promoting a novel glutamate biosynthetic pathway in the brain,” Cell, doi: 10.1016/j.cell.2018.04.014, 2018.

Teenagers and sleep. It’s certainly a passionate subject for many American parents … and those in China. University of Delaware’s Xiaopeng Ji is investigating the relationship between midday-napping behaviors and neurocognitive function in early adolescents. In a study funded by the National Institutes of Health, the School of Nursing assistant professor and principal investigator Jianghong Liu (University of Pennsylvania) turned to the Chinese classroom. With participants from schools in Jintan, she measured midday napping, nighttime sleep duration and sleep quality, and performance on multiple neurocognitive tasks.

Ji is interested in the relationship between sleep and cognition. Because of the intensive learning and education demands, the adolescent population is key. Neurocognitive functioning is essential for learning, emotion and behavior control. Her findings suggest that an association between habitual midday napping and neurocognitive function, especially in China, where midday napping is a cultural practice.

“Daytime napping is quite controversial in the United States. In Western culture, the monophasic sleep pattern is considered a marker of brain maturation,” Ji said. “In China, time for napping is built into the post-lunch schedule for many adults in work settings and students at schools.”

Ji has studied the circadian rhythm of sleep (a person’s 24-hour cycle). A developmental change takes place in circadian rhythm during adolescence; teenagers’ rhythm shifts one to two hours later than the preadolescent period.

“This phase delay is biologically driven in adolescents,” Ji said. “Think about that in a school schedule. Teenagers have to get up early for school. And, with this phase delay of going to bed later, they are at-risk for chronic sleep deprivation.”

Ji explained that these adolescents may experience impaired neurocognitive function, which makes paying attention in school even more difficult. Memory and reasoning ability also suffer.

A circadian dip occurs daily from 12 to 2 p.m. During that period, adolescents are more likely to fall asleep. In a U.S. school, a student does not have a formal opportunity to do so.

“Throughout childhood, U.S. kids experience decreases in napping tendencies. Kids are trained to remove their midday napping behavior,” said Ji. “Conversely in China, the school schedule allows children to maintain it.”

Researchers have taken a friend or foe mentality towards napping. Many consider a midday snooze as needed compensation for nighttime sleep deprivation; another faction believes daytime napping continually interferes with nighttime sleep. Many studies invite people to a lab setting — experimentally imposing the nap — and find the aforementioned cognitive benefits. But Ji said that’s difficult to correlate with habitual sleep at home.

“The results from lab studies may be different from what the population is habitually doing at home — sleeping in their own bed,” Ji said.

Lots of research exists on adults, but that’s not the case for adolescents. This lack of literature motivated Ji to take on the task. And since the American school schedule was a barrier to finding more information, researchers used Chinese data in the University of Delaware and University of Pennsylvania collaborative study.

Key findings

Ji investigated two dimensions of nap behavior — frequency and duration. Routine nappers, who napped five to seven days in a week, had sustained attention, better nonverbal reasoning ability and spatial memory. How long to nap is also an important question? The sweet spot is between 30 to 60 minutes. A nap longer than one hour interferes with circadian rhythm. Participants who slept between 30 to 60 minutes produced better accuracy in attention tasks as well as faster speed. She recommends not to nap after 4 p.m., nor over-nap.

Researchers were surprised to find a positive relationship between midday napping and nighttime sleep, which is different than the literature. Habitual nappers (who napped more often) tended to have a better nighttime sleep.

“That’s different than the findings in the United States, where napping may serve as a function to replace sleep lost from the previous night. Consequently, that may interfere with the following night’s sleep,” Ji said. “In China, a midday nap is considered a healthy lifestyle. Routine nappers are more likely to experience healthy nighttime sleep. So routine nappers are essentially trained to sleep well and sleep more at night.”

Ji was clear that this study was observational. At this point, she cannot conclude causality. She hopes this line of research can inform future studies and public health policy.

By Conn Hastings

A study recently published in open-access journal Frontiers in Psychology finds that 9-10 year-old children are significantly more attentive and engaged with their schoolwork following an outdoor lesson in nature. This “nature effect” allowed teachers to teach uninterrupted for almost twice as long during a subsequent indoor lesson. The results suggest that outdoor lessons may be an inexpensive and convenient way to improve student engagement in education — a major factor in academic achievement.

Scientists have known for a while that natural outdoor environments can have a variety of beneficial effects on people. People exposed to parks, trees or wildlife can experience benefits such as physical activity, stress reduction, rejuvenated attention and increased motivation. In children, studies have shown that even a view of greenery through a classroom window could have positive effects on students’ attention.

However, many teachers may be reluctant to hold a lesson outdoors, as they might worry that it could overexcite the children, making it difficult for them to concentrate on their schoolwork back in the classroom. Ming Kuo, a scientist at the University of Illinois at Urbana-Champaign, and her colleagues set out to investigate this, and hypothesized that an outdoor lesson in nature would result in increased classroom engagement in indoor lessons held immediately afterwards.

“We wanted to see if we could put the nature effect to work in a school setting,” says Kuo. “If you took a bunch of squirmy third-graders outdoors for lessons, would they show a benefit of having a lesson in nature, or would they just be bouncing off the walls afterward?”

The researchers tested their hypothesis in third graders (9-10 years old) in a school in the Midwestern United States. Over a 10-week period, an experienced teacher held one lesson a week outdoors and a similar lesson in her regular classroom, and another, more skeptical teacher did the same. Their outdoor “classroom” was a grassy spot just outside the school, in view of a wooded area.

After each outdoor or indoor lesson, the researchers measured how engaged the students were. They counted the number of times the teacher needed to redirect the attention of distracted students back to their schoolwork during the observation, using phrases such as “sit down” and “you need to be working”. The research team also asked an outside observer to look at photos taken of the class during the observation period and score the level of class engagement, without knowing whether the photos were taken after an indoor or outdoor lesson. The teachers also scored class engagement.

The team’s results show that children were more engaged after the outdoor lessons in nature. Far from being overexcited and inattentive immediately after an outdoor lesson, students were significantly more attentive and engaged with their schoolwork. The number of times the teacher had to redirect a student’s attention to their work was roughly halved immediately after an outdoor lesson.

“Our teachers were able to teach uninterrupted for almost twice as long at a time after the outdoor lesson,” says Kuo, “and we saw the nature effect with our skeptical teacher as well.”

The researchers plan to do further work to see if the technique can work in other schools and for less experienced teachers. If so, regular outdoor lessons could be an inexpensive and convenient way for schools to enhance student engagement and performance. “We’re excited to discover a way to teach students and refresh their minds for the next lesson at the same time,” says Kuo. “Teachers can have their cake and eat it too.”

Children more engaged and attentive following outdoor lesson in nature

The more scientists study pigeons, the more they learn how their brains—no bigger than the tip of an index finger—operate in ways not so different from our own.

In a new study from the University of Iowa, researchers found that pigeons can categorize and name both natural and manmade objects—and not just a few objects. These birds categorized 128 photographs into 16 categories, and they did so simultaneously.

Ed Wasserman, UI professor of psychology and corresponding author of the study, says the finding suggests a similarity between how pigeons learn the equivalent of words and the way children do.

“Unlike prior attempts to teach words to primates, dogs, and parrots, we used neither elaborate shaping methods nor social cues,” Wasserman says of the study, published online in the journal Cognition. “And our pigeons were trained on all 16 categories simultaneously, a much closer analog of how children learn words and categories.”

For researchers like Wasserman, who has been studying animal intelligence for decades, this latest experiment is further proof that animals—whether primates, birds, or dogs—are smarter than once presumed and have more to teach scientists.

“It is certainly no simple task to investigate animal cognition; But, as our methods have improved, so too have our understanding and appreciation of animal intelligence,” he says. “Differences between humans and animals must indeed exist: many are already known. But, they may be outnumbered by similarities. Our research on categorization in pigeons suggests that those similarities may even extend to how children learn words.”

Wasserman says the pigeon experiment comes from a project published in 1988 and featured in The New York Times in which UI researchers discovered pigeons could distinguish among four categories of objects.

This time, the UI researchers used a computerized version of the “name game” in which three pigeons were shown 128 black-and-white photos of objects from 16 basic categories: baby, bottle, cake, car, cracker, dog, duck, fish, flower, hat, key, pen, phone, plan, shoe, tree. They then had to peck on one of two different symbols: the correct one for that photo and an incorrect one that was randomly chosen from one of the remaining 15 categories. The pigeons not only succeeded in learning the task, but they reliably transferred the learning to four new photos from each of the 16 categories.

Pigeons have long been known to be smarter than your average bird—or many other animals, for that matter. Among their many talents, pigeons have a “homing instinct” that helps them find their way home from hundreds of miles away, even when blindfolded. They have better eyesight than humans and have been trained by the U. S. Coast Guard to spot orange life jackets of people lost at sea. They carried messages for the U.S. Army during World Wars I and II, saving lives and providing vital strategic information.

UI researchers say their expanded experiment represents the first purely associative animal model that captures an essential ingredient of word learning—the many-to-many mapping between stimuli and responses.

“Ours is a computerized task that can be provided to any animal, it doesn’t have to be pigeons,” says UI psychologist Bob McMurray, another author of the study. “These methods can be used with any type of animal that can interact with a computer screen.”

McMurray says the research shows the mechanisms by which children learn words might not be unique to humans.

“Children are confronted with an immense task of learning thousands of words without a lot of background knowledge to go on,” he says. “For a long time, people thought that such learning is special to humans. What this research shows is that the mechanisms by which children solve this huge problem may be mechanisms that are shared with many species.”

Wasserman acknowledges the recent pigeon study is not a direct analogue of word learning in children and more work needs to be done. Nonetheless, the model used in the study could lead to a better understanding of the associative principles involved in children’s word learning.

“That’s the parallel that we’re pursuing,” he says, “but a single project—however innovative it may be—will not suffice to answer such a provocative question.”