Posts tagged neuroscience
Articles and news from the latest research reports.
Publication in Nature Showcases Most Comprehensive Wiring Diagram of the Mammalian Brain To Date
Researchers from the Allen Institute for Brain Science have published the first comprehensive, large-scale data set on how the brain of a mammal is wired, providing a groundbreaking data resource and fresh insights into how the nervous system processes information. Their landmark paper in this week’s issue of the journal Nature both describes the publicly available Allen Mouse Brain Connectivity Atlas, and demonstrates the exciting knowledge that can be gleaned from this valuable resource.
(Image: Connectivity Dot-o-Gram)
“Understanding how the brain is wired is among the most crucial steps to understanding how the brain encodes information,” explains Hongkui Zeng, Senior Director of Research Science at the Allen Institute for Brain Science. “The Allen Mouse Brain Connectivity Atlas is a standardized, quantitative, and comprehensive resource that will stimulate exciting investigations around the entire neuroscience community, and from which we have already gleaned unprecedented details into how structures are connected inside the brain.”
Using the data, Allen Institute scientists were able to demonstrate that there are highly specific patterns in the connections among different brain regions, and that the strengths of these connections vary with greater than five orders of magnitudes, balancing a small number of strong connections with a large number of weak connections. This publication comes just as the research team wraps up more than four years of work to collect and make publicly available the data behind the Allen Mouse Brain Connectivity Atlas project, with the completion of the Atlas announced in March 2014.
(Source: alleninstitute.org)
A Critical Window into the Developing Human Brain Profiled in Nature
First major report using data from the BrainSpan Atlas of the Developing Human Brain shines a light on where genes are turned on in the brain during mid-pregnancy, what goes wrong in developmental disorders like autism, and what makes human brains unique.
Researchers at the Allen Institute for Brain Science have generated a high-resolution blueprint for how to build a human brain, with a detailed map of where different genes are turned on and off during mid-pregnancy at unprecedented anatomical resolution. This first major report using data from the BrainSpan Atlas of the Developing Human Brain is published in the journal Nature this week. The data provide exceptional insight into diseases like autism that are linked to early brain development, and to the origins of human uniqueness. The rich data set is publicly available to everyone via the Allen Brain Atlas data portal.
“Knowing where a gene is expressed in the brain can provide powerful clues about what its role is,” says Ed Lein, Investigator at the Allen Institute for Brain Science. “This atlas gives a comprehensive view of which genes are on and off in which specific nuclei and cell types while the brain is developing during pregnancy. This means that we have a blueprint for human development: an understanding of the crucial pieces necessary for the brain to form in a normal, healthy way, and a powerful way to investigate what goes wrong in disease.”
This paper represents the first major report to make use of data collected for the BrainSpan Atlas of the Developing Human Brain, a big science consortium initiative which seeks to create a map of the transcriptome across the entire course of human development. “Coming on the first anniversary of the BRAIN Initiative, this is a terrific example of the potential for public-private partnerships to accelerate progress in neuroscience,” says Lein.
Thomas R. Insel, Director of the National Institute of Mental Health, praises the BrainSpan Atlas as an already invaluable tool to researchers. “While we have had previous reports of molecular and cellular changes during human brain growth, the BrainSpan Atlas is the first comprehensive map of the dramatic trajectory of gene expression across prenatal and postnatal development,” he says. “This atlas is already transforming the way scientists approach human brain development and neurodevelopmental disorders like autism and schizophrenia. Although the many genes associated with autism and schizophrenia don’t show a clear relationship to each other in the adult brain, the BrainSpan Atlas reveals how these diverse genes are connected in the prenatal brain.”
(Source: alleninstitute.org)
Study finds link between child’s obesity and cognitive function
A new University of Illinois study finds that obese children are slower than healthy-weight children to recognize when they have made an error and correct it. The research is the first to show that weight status not only affects how quickly children react to stimuli but also impacts the level of activity that occurs in the cerebral cortex during action monitoring.
“I like to explain action monitoring this way: when you’re typing, you don’t have to be looking at your keyboard or your screen to realize that you’ve made a keystroke error. That’s because action monitoring is occurring in your brain’s prefrontal cortex,” said Charles Hillman, a U of I professor of kinesiology and faculty member in the U of I’s Division of Nutritional Sciences.
As an executive control task that requires organizing, planning, and inhibiting, action monitoring requires people to be computational and conscious at all times as they process their behavior. Because these higher-order cognitive processes are needed for success in mathematics and reading, they are linked with success in school and positive life outcomes, he said.
“Imagine a child in a math class constantly checking to make sure she’s carrying the digit over when she’s adding. That’s an example,” he added.
In the study, the scientists measured the behavioral and neuroelectric responses of 74 preadolescent children, half of them obese, half at a healthy weight. Children were fitted with caps that recorded electroencephalographic activity and asked to participate in a task that presented left- or right-facing fish, predictably facing in either the same or the opposite direction. Children were asked to press a button based on the direction of the middle (that is, target) fish. The flanking fish either pointed in the same direction (facilitating) or in the opposite direction (hindering) their ability to respond successfully.
“We found that obese children were considerably slower to respond to stimuli when they were involved in this activity,” Hillman said.
The researchers also found that healthy-weight children were better at evaluating their need to change their behavior in order to avoid future errors.
“The healthy-weight kids were more accurate following an error than the obese children were, and when the task required greater amounts of executive control, the difference was even greater,” he reported.
A second evaluation measured electrical activity in the brain “that occurs at the intersection of thought and action,” Hillman said. “We can measure what we call error-related negativity (ERN) in the electrical pattern that the brain generates following errors. When children made an error, we could see a larger negative response. And we found that healthy-weight children are better able to upregulate the neuroelectric processes that underlie error evaluation.”
Scientists in the Hillman lab and elsewhere have seen a connection between healthy weight and academic achievement, “but a study like this helps us understand what’s happening. There are certainly physiological differences in the brain activity of obese and healthy-weight children. It’s exciting to be able to use functional brain imaging to see the way children’s weight affects the aspects of cognition that influence and underlie achievement,” said postdoctoral researcher and co-author Naiman Khan.
(Source: news.aces.illinois.edu)
Sport makes muscles and nerves fit
Endurance sport does not only change the condition and fitness of muscles but also simultaneously improves the neuronal connections to the muscle fibers based on a muscle-induced feedback. This link has been discovered by Christoph Handschin’s research group at the Biozentrum of the University of Basel. The group was also able to induce the same effect through raising the protein concentration of PGC1α in the muscle. Their findings, which are also interesting in regard to muscle and nerve disorders such as muscle wasting and ALS, have been published in the current issue of the journal “Nature Communications”.
It’s springtime – the start signal for all joggers. It is well known that a regular run through the forest makes your muscles fit. Responsible for this effect is the protein PGC1α, which plays a central role in the adaptation of muscles to training. The research team led by Prof. Christoph Handschin has discovered that such endurance training not only affects the condition of the muscles but also the upstream synaptic neuronal connections in a muscle-dependent manner.
PGC1α does not only make muscles fit…
How do muscles change during muscle training or in muscle disease? Christoph Handschin and his team have been addressing this question for some years. In the past, they have already shown that the protein PGC1α plays a key role in the adaptation of the muscle by regulating the genes that cause the muscles to change accordingly to meet the more demanding requirements. When muscle is inactive or ill, only a low concentration of PGC1α is present. However, when the muscle is challenged, the PGC1α level increases. Through artificial elevation of the PGC1α concentration, it is possible to stimulate muscle endurance.
… but also the nerve connections
Now, the scientists have been able to demonstrate that the increase in muscle PGC1α concentration also improves the upstream synaptic nerve connections to the result of this feedback from muscle to the motor neuron: The health of the synapse improves and its activation pattern adapts to meet the requirements of the muscle. Until now, the influence of the muscle on the synaptic connection was primarily recognized in embryonic development. “That in adults, where the nerve and muscular systems are fully developed, not only the muscle changes due to an increase in PGC1α concentration but also a muscle-controlled improvement in the entire nerve and muscular system takes place, was completely unexpected and a great surprise to us”, says Handschin. “Our current aim is to identify the exact signal that leads to this stabilization of the synaptic connections, in order to apply this for treating muscle disorders.”
…and helps in the treatment of muscle and nerve disorders
A direct therapeutic application of the research findings in illnesses such as muscle wasting and amyotrophic lateral sclerosis (ALS) is already conceivable for Christoph Handschin. “In patients, whose muscles due to their illness are too weak to move on their own, an increase in PGC1α levels could strengthen muscles and nerves until the patients can move enough to finally do some physical therapy and to further improve their mobility”, he explains. After the pharmacological improvement of the health status of the muscles and nerves, the patient could independently continue their treatment through practicing endurance sports.
Dog watch - How attention changes in the course of a dog’s life
Dogs are known to be Man’s best friend. No other pet has adjusted to Man’s lifestyle as this four-legged animal. Scientists at the Messerli Research Institute at the Vetmeduni Vienna, have been the first to investigate the evolution of dogs’ attentiveness in the course of their lives and to what extent they resemble Man in this regard. The outcome: dogs’ attentional and sensorimotor control developmental trajectories are very similar to those found in humans. The results were published in the journal Frontiers in Psychology.
Dogs are individual personalities, possess awareness, and are particularly known for their learning capabilities, or trainability. To learn successfully, they must display a sufficient quantity of attention and concentration. However, the attentiveness of dogs’ changes in the course of their lives, as it does in humans. The lead author Lisa Wallis and her colleagues investigated 145 Border Collies aged 6 months to 14 years in the Clever Dog Lab at the Vetmeduni Vienna and determined, for the first time, how attentiveness changes in the entire course of a dog’s life using a cross-sectional study design.
Humans are more interesting for dogs than objects
To determine how rapidly dogs of various age groups pay attention to objects or humans, the scientists performed two tests. In the first situation the dogs were confronted with a child’s toy suspended suddenly from the ceiling. The scientists measured how rapidly each dog reacted to this occurrence and how quickly the dogs became accustomed to it. Initially all dogs reacted with similar speed to the stimulus, but older dogs lost interest in the toy more rapidly than younger ones did.
In the second test situation, a person known to the dog entered the room and pretended to paint the wall. All dogs reacted by watching the person and the paint roller in the person’s hands for a longer duration than the toy hanging from the ceiling.
Wallis’ conclusion: “So-called social attentiveness was more pronounced in all dogs than “non-social” attentiveness. The dogs generally tended to react by watching the person with the object for longer than an object on its own. We found that older dogs - like older human beings - demonstrated a certain calmness. They were less affected by new items in the environment and thus showed less interest than younger dogs.”
Selective attention is highest in mid-adulthood
In a further test the scientists investigated so-called selective attention. The dogs participated in an alternating attention task, where they had to perform two tasks consecutively. First, they needed to find a food reward thrown onto the floor by the experimenter, then after eating the food, the experimenter waited for the dog to establish eye contact with her. These tasks were repeated for a further twenty trials. The establishment of eye contact was marked by a clicking sound produced by a “clicker” and small pieces of hot dog were used as a reward. The time spans to find the food and look up into the face were measured. With respect to both time spans, middle-aged dogs (3 to 6 years) reacted most rapidly.
Under these test conditions, sensorimotor abilities were highest among dogs of middle age. Younger dogs fared more poorly probably because of their general lack of experience. Motor abilities in dogs as in humans deteriorate with age. Humans between the age of 20 and 39 years experience a similar peak in sensorimotor abilities,” says Wallis.
Adolescent dogs have the steepest learning curve
Dogs also go through a difficult phase during adolescence (1-2 years) which affects their ability to pay attention. This phase of hormonal change may be compared to puberty in Man. Therefore, young dogs occasionally reacted with some delay to the clicker test. However, Wallis found that adolescent dogs improved their performance more rapidly than other age groups after several repetitions of the clicker test. In other words, the learning curve was found to be steepest in puberty. “Thus, dogs in puberty have great potential for learning and therefore trainability” says Wallis.
Dogs as a model for ADHD and Alzheimer’s disease
As the development of attentiveness in the course of a dog’s life is similar to human development in many respects, dogs make appropriate animal models for various human psychological diseases. For instance, the course of diseases like ADHD (attention deficit/hyperactivity disorder) or Alzheimer’s can be studied by observing the behavior of dogs. In her current project Wallis is investigating the effects of diet on cognition in older dogs together with her colleague Durga Chapagain. The scientists are still looking for dog owners who would like to participate in a long-term study.
Switching Brain Cells with Less Light
Networked nerve cells are the control center of organisms. In a nematode, 300 nerve cells are sufficient to initiate complex behavior. To understand the properties of the networks, researchers switch cells on and off with light and observe the resulting behavior of the organism. In the Science journal, scientists now present a protein that facilitates the control of nerve cells by light. It might be used as a basis of studies of diseases of the nervous system.
(Image caption: Nerve cells form networks that can process signals. Photo: J. Wietek/HU Berlin).
To switch a nerve cell with light, certain proteins forming ion channels in the cell membrane are used. These proteins are called channelrhodopsins. If light strikes the channels, they open and ions enter and render the cell specifically active or inactive. In this way, a very fine tool is obtained to study functions in the network of nerve cells. So far, however, large amounts of light have been required and only closely limited areas in the network could be switched. The ChlocC channelrhodopsin presented now reacts about 10,000 times more sensitively to light than other proteins used so far for switching off nerve cells.
“For the modification of the protein, we analyzed its structure on the computer,” Marcus Elstner, KIT, explains. The theoretical chemist and his team modeled the proteins that consist of about 5000 atoms. For this purpose, they used the highest-performance computers of KIT’s computing center, the Steinbuch Centre for Computing, SCC. Together with the protein environment, i.e. the cell membrane and cell water, about 100,000 atoms had to be considered for the computations that took several weeks. “It was found that ion conductivity of the channel is essentially based on three amino acids in the central region, i.e. on about 50 atoms in the channel only.” By exchanging the amino acids, scientists have now succeeded in increasing the sensitivity of the ion channel.
Light-activated ion channels, the so-called channelrhodopsins, from microalgae have been used since 2005. In neural sections or living transgenic model organisms, such as flies, zebrafish, or mice, they allow for the specific activation of selected cells with light. Thus, understanding of their role in the cell structure can be improved. This technology is known as optogenetics and applied widely. In the past years, it contributed to the better understanding of the biology of signal processing. So far inaccessible neural pathways were mapped and many relationships were discovered among proteins, cells, tissues, and functions of the nervous system.
Within the framework of the study reported in the latest Science issue, researchers from Karlsruhe, Hamburg, and Berlin developed the ion channels further. Jonas Wietek and Nona Adeishvili working in the team of Peter Hegemann at the Humboldt-Universität Berlin have succeeded in identifying the selectivity filter of the channelrhodopsins and in modifying it such that negatively charged chloride ions are conducted. These chloride-conducting channels have been called ChlocC by the scientists. Hiroshi Watanabe from the team of Marcus Elstner, Karlsruhe Institute of Technology (KIT), computed ion distribution in the protein and visualized the increased chloride distribution. Simon Wiegert from the team of Thomas Oertner of the Center for Molecular Neurobiology, Hamburg, demonstrated that ChlocC can be introduced into selected neurons for the inactivation of the latter with very small light intensities similar to the processes taking place in the living organism. With ChloC a novel optogenetic tool is now available that can be used in neurosciences to study the switching of neural networks together with the already known light-activated cation channels that mainly conduct sodium ions and protons. This fundamental knowledge might help better understand the mechanisms of diseases like epilepsy and Parkinson’s. In some years from now, this may give rise to therapy concepts, which might be much more specific than the medical drugs used today.
(Source: kit.edu)
Some innate preferences shape the sound of words from birth
Languages are learned, it’s true, but are there also innate bases in the structure of language that precede experience? Linguists have noticed that, despite the huge variability of human languages, here are some preferences in the sound of words that can be found across languages. So they wonder whether this reflects the existence of a universal, innate biological basis of language. A SISSA study provides evidence to support this hypothesis, demonstrating that certain preferences in the sound of words are already active in newborn infants.
Take the sound “bl”: how many words starting with that sound can you think of? Blouse, blue, bland… Now try with “lb”: how many can you find? None in English and Italian, and even in other languages such words either don’t exist or are extremely rare. Human languages offer several examples of this kind, and this indicates that in forming words we tend to prefer certain sound combinations to others, irrespective of which language we speak. The fact that this occurs across languages has prompted linguists to hypothesize the existence of biological bases of language (in born and universal) which precede language learning in humans. Finding evidence to support his hypothesis is, however, far from easy and the debate between the proponents of this view and those who believe that language is merely the result of learning is still open. But proof supporting the “universalist” hypothesis has now been provided by a new study conducted by a research team of the International School for Advanced Studies (SISSA) in Trieste and just published in the journal PNAS.
David Gomez, a SISSA research scientist working under the supervision of Jacques Mehler and first author of the paper, and his coworkers decided to observe the brain activity of newborns. “In fact, if it is possible to demonstrate that these preferences are already present within days from birth, when the newborn baby is still unable to speak and presumably has very limited language knowledge, then we can infer that there is an inborn bias that prefers certain words to others”, comments Gomez.
“To monitor the newborns’ brain activity we used a non-invasive technique, i.e., functional near-infrared spectroscopy”, explains Marina Nespor, a SISSA neuroscientist who participated in the study. During the experiments the newborns would listen to words starting with normally “preferred” sounds (like “bl”) and others with uncommon sounds (“lb”). “What we found was that the newborns’ brains reacted in a significantly different manner to the two types of sound” continues Nespor.
“The brain regions that are activated while the newborns are listening react differently in the two cases”, comments Gomez, “and reflect the preferences observed across languages, as well as the behavioural responses recorded in similar experiments carried out in adults”. “It’s difficult to imagine what languages would sound like if humans didn’t share a common knowledge base”, concludes Gomez. “We are lucky that this common base exists. This way, our children are born with an ability to distinguish words from “non-words” ever since birth, regardless of which language they will then go on to learn”.
Team finds a better way to grow motor neurons from stem cells
Researchers report they can generate human motor neurons from stem cells much more quickly and efficiently than previous methods allowed. The finding, described in Nature Communications, will aid efforts to model human motor neuron development, and to understand and treat spinal cord injuries and motor neuron diseases such as amyotrophic lateral sclerosis (ALS).
The new method involves adding critical signaling molecules to precursor cells a few days earlier than previous methods specified. This increases the proportion of healthy motor neurons derived from stem cells (from 30 to 70 percent) and cuts in half the time required to do so.
“We would argue that whatever happens in the human body is going to be quite efficient, quite rapid,” said University of Illinois cell and developmental biology professor Fei Wang, who led the study with visiting scholar Qiuhao Qu and materials science and engineering professor Jianjun Cheng. “Previous approaches took 40 to 50 days, and then the efficiency was very low – 20 to 30 percent. So it’s unlikely that those methods recreate human motor neuron development.”
Qu’s method produced a much larger population of mature, functional motor neurons in 20 days.
The new approach will allow scientists to induce mature human motor neuron development in cell culture, and to identify the factors that are vital to that process, Wang said.
Stem cells are unique in that they can adopt the shape and function of a variety of cell types. Generating neurons from stem cells (either embryonic stem cells or those “induced” to revert back to an embryo-like state) requires adding signaling molecules to the cells at critical moments in their development.
Wang and other colleagues previously discovered a molecule (called compound C) that converts stem cells into “neural progenitor cells,” an early stage in the cells’ development into neurons. But further coaxing these cells to become motor neurons presented unusual challenges.
Previous studies added two important signaling molecules at Day 6 (six days after exposure to compound C), but with limited success in generating motor neurons. In the new study, Qu discovered that adding the signaling molecules at Day 3 worked much better: The neural progenitor cells quickly and efficiently differentiated into motor neurons.
This indicates that Day 3 represents a previously unrecognized neural progenitor cell stage, Wang said.
The new approach has immediate applications in the lab. Watching how stem cells (derived from ALS patients’ own skin cells, for example) develop into motor neurons will offer new insights into disease processes, and any method that improves the speed and efficiency of generating the motor neurons will aid scientists. The cells can also be used to screen for drugs to treat motor neuron diseases, and may one day be used therapeutically to restore lost function.
“To have a rapid, efficient way to generate motor neurons will undoubtedly be crucial to studying – and potentially also treating – spinal cord injuries and diseases like ALS,” Wang said.
‘Sewing machine’ idea gives insight into origins of Alzheimer’s
Researchers at Lancaster University have invented a new imaging tool inspired by the humble sewing machine which is providing fresh insight into the origins of Alzheimer’s and Parkinson’s disease.
These diseases are caused by tiny toxic proteins too small to be studied with traditional optical microscopy.
Previously it was thought that Alzheimer’s was caused by the accumulation of long ‘amyloid’ fibres at the centre of senile plaques in the brain, due to improper folding of a protein called amyloid-β.
But new research suggests that these fibres and plaques are actually the body’s protective response to the presence of even smaller, more toxic structures made from amyloid-β called ‘oligomers’.
Existing techniques are not sufficient to get a good look at these proteins; optical microscopy does not provide enough resolution at this scale, and electron microscopy gives the resolution but not the contrast.
To solve the problem, Physicist Dr Oleg Kolosov and his team at Lancaster have developed a new imaging technique - Ultrasonic Force Microscopy (UFM) - inspired by the motion of a sewing machine. Their work has been published in Scientific Reports.
Dr Kolosov said: “By using a vibrating scanner, which moves quickly up and down like the foot of a sewing machine needle, the friction between the sample and the scanner was reduced – resulting in a better quality, and high contrast nanometre scale resolution image.”
It is one of a new generation of tools being developed worldwide to bring the oligomers into focus, enabling medical researchers to understand how they behave.
At Lancaster, Claire Tinker used UFM to image these oligomers. To help see them more clearly she needed to increase the contrast of the image and used poly-L-lysine (PLL) which kept the proteins stuck to the slides as the vibrating scanner was passed over them.
Lancaster University Biomedical Scientist Professor David Allsop said: “These high quality images are vitally important if we are to understand the pathways involved in formation of these oligomers, and this new technique will now be used to test the effects of inhibitors of oligomer formation that we are developing as a possible new treatment for Alzheimer’s disease.”
The technique worked so well that the team now hopes to develop it so that oligomer formation can be monitored as they are made in real time.
This would give researchers a clearer understanding of the early phases of Alzheimer’s and Parkinson’s and could potentially be one way of developing a future test for these diseases.
(Source: alphagalileo.org)
When we watch a movie, our brains react to it immediately in a way similar to other people’s brains.
Researchers at Aalto University in Finland have succeeded in developing a method fast enough to observe immediate changes in the function of the brain even when watching a movie. By employing movies it was possible to investigate the function of the human brain in experimental conditions that are close to natural. Traditionally, in neuroscience research, simple stimuli, such as checkerboard patterns or single images, have been used.
Viewing a movie creates multilevel changes in the brain function. Despite the complexity of the stimulus, the elicited brain activity patterns show remarkable similarities across different people – even at the time scale of fractions of seconds.
The analysis revealed important similarities between brain signals of different people during movie viewing. These similar kinds or synchronized signals were found in brain areas that are connected with the early-stage processing of visual stimuli, detection of movement and persons, motor coordination and cognitive functions. The results imply that the contents of the movie affected certain brain functions of the subjects in a similar manner, explains Kaisu Lankinen the findings of her doctoral research.
So far, studies in this field have mainly been based on functional magnetic resonance imaging (fMRI). However, given the superior temporal resolution, within milliseconds, magnetoencephalography (MEG) is able to provide more complete picture of the fast brain processes. With the help of MEG and new analysis methods, investigation of significantly faster brain processes is possible and it enables detection of brain activity in frequencies higher than before.
In the novel analysis, brain imaging was combined with machine-learning methodology, with which signals of a similar form were mined from the brain data.
The research result was recently published in the NeuroImage journal.