Posts tagged science
Articles and news from the latest research reports.
Forgetting Is Actively Regulated
In order to function properly, the human brain requires the ability not only to store but also to forget: Through memory loss, unnecessary information is deleted and the nervous system retains its plasticity. A disruption of this process can lead to serious mental disorders. Basel scientists have now discovered a molecular mechanism that actively regulates the process of forgetting. The renowned scientific journal “Cell” has published their results.
The human brain is build in such a way, that only necessary information is stored permanently - the rest is forgotten over time. However, so far it was not clear if this process was active or passive. Scientists from the transfaculty research platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now found a molecule that actively regulates memory loss. The so-called musashi protein is responsible for the structure and function of the synaptic connections of the brain, the place where information is communicated from one neuron to the next.
Using olfactory conditioning, the researchers Attila Stetak and Nils Hadziselimovic first studied the learning abilities of genetically modified ringworms (C. elegans) that were lacking the musashi protein. The experiments showed that the worms exhibited the same learning skills as unmodified animals. However, with extended duration of the experiment, the scientists discovered that the mutants were able to remember the new information much better. In other words: The genetically modified worms lacking the musashi protein were less forgetful.
Forgetting is no coincidence
Further experiments showed that the protein inhibits the synthesis of molecules responsible for the stabilization of synaptic connections. This stabilization seems to play an important role in the process of learning and forgetting. The researchers identified two parallel mechanisms: One the one hand, the protein adducin stimulates the growth of synapses and therefore also helps to retain memory; on the other hand, the musashi protein actively inhibits the stabilization of these synapses and thus facilitates memory loss. Therefore, it is the balance between these two proteins that is crucial for the retention of memories.
Forgetting is thus not a passive but rather an active process and a disruption of this process may result in serious mental disorders. The musashi protein also has interesting implications for the development of drugs trying to prevent abnormal memory loss that occurs in diseases such as Alzheimer’s. Further studies on the therapeutic possibilities of this discovery will be done.
Human brains ‘hard-wired’ to link what we see with what we do
Your brain’s ability to instantly link what you see with what you do is down to a dedicated information ‘highway’, suggests new UCL-led research.
For the first time, researchers from UCL and Cambridge University have found evidence of a specialised mechanism for spatial self-awareness that combines visual cues with body motion.
Standard visual processing is prone to distractions, as it requires us to pay attention to objects of interest and filter out others. The new study has shown that our brains have separate ‘hard-wired’ systems to visually track our own bodies, even if we are not paying attention to them. In fact, the newly-discovered network triggers reactions even before the conscious brain has time to process them.
The researchers discovered the new mechanism by testing 52 healthy adults in a series of three experiments. In all experiments, participants used robotic arms to control cursors on two-dimensional displays, where cursor motion was directly linked to hand movement. Their eyes were kept fixed on a mark at the centre of the screen, confirmed with eye tracking.
In the first experiment, participants controlled two separate cursors with their left and right hands, both equally close to the centre. The goal was to guide each cursor to a corresponding target at the top of the screen. Occasionally the cursor or target on one side would jump left or right, requiring participants to take corrective action. Each jump was ‘cued’ with a flash on one side, but this was random so did not always correspond to the side about to change.
Unsurprisingly, people reacted faster to target jumps when their attention was drawn to the ‘correct’ side by the cue. However, reactions to cursor jumps were fast regardless of cuing, suggesting that a separate mechanism independent of attention is responsible for tracking our own movements.
“The first experiment showed us that we react very quickly to changes relating to objects directly under our own control, even when we are not paying attention to them,” explains Dr Alexandra Reichenbach of the UCL Institute of Cognitive Neuroscience, lead author of the study. “This provides strong evidence for a dedicated neural pathway linking motor control to visual information, independently of the standard visual systems that are dependent on attention.”
The second experiment was similar to the first, but also introduced changes in brightness to demonstrate the attention effect on the visual perception system. In the third experiment, participants had to guide one cursor to its target in the presence of up to four dummy targets and cursors, ‘distractors’, alongside the real ones. In this experiment, responses to cursor jumps were less affected by distractors than responses to target jumps. Reactions to cursor jumps remained vigorous with one or two distractors, but were significantly decreased when there were four.
“These results provide further evidence of a dedicated ‘visuomotor binding’ mechanism that is less prone to distractions than standard visual processing,’ says Dr Reichenbach. “It looks like the specialised system has a higher tolerance for distractions, but in the end it is still affected. Exactly why we evolved a separate mechanism remains to be seen, but the need to react rapidly to different visual cues about ourselves and the environment may have been enough to necessitate a specialised pathway.”
The newly-discovered system could explain why some schizophrenia patients feel like their actions are controlled by someone else.
“Schizophrenia often manifests as delusion of control, and a dysfunction in the visuomotor mechanism identified in this study might be a cause for this symptom,” explains Dr Reichenbach. “If someone does not automatically link corresponding visual cues with body motion, then they might have the feeling that they are not controlling their movements. We would need further research to confirm this, and it would be fascinating to see how schizophrenia patients perform in these experiments.”
These findings could also explain why people with even the most advanced prosthetic limbs can have trouble coordinating movements.
“People often describe their prosthetic limbs as feeling ‘other’, not a true extension of their body,’ says Dr Reichenbach. “Even on the best prosthetic hands, if the observed movement of the fingers is not exactly what you would expect, then it will not feel like you are in direct control. These small details might have a big effect on how people perceive prostheses.”
(Source: ucl.ac.uk)
These Boosts Are Made For Walkin’: Study Reveals that Movement Kicks Visual System into Higher Gear
Whether you’re a Major League outfielder chasing down a hard-hit ball or a lesser mortal navigating a busy city sidewalk, it pays to keep a close watch on your surroundings when walking or running. Now, new research by UC San Francisco neuroscientists suggests that the body may get help in these fast-changing situations from a specialized brain circuit that causes visual system neurons to fire more strongly during locomotion.
There has been a great deal of research on changes among different brain states during sleep, but the new findings, reported in the March 13 issue of Cell, provide a compelling example of a change in state in the awake brain.
It has long been known that nerve cells in the visual system fire more strongly when we pay close attention to objects than when we view scenes more passively. But the new research, led by Yu Fu, PhD, a postdoctoral fellow in the UCSF lab of senior author Michael P. Stryker, PhD, the W.F. Ganong Professor of Physiology, breaks new ground, mapping out a visual system amplifier that is directly activated by walking or running.
Though this circuit has not yet been shown to exist in humans, Stryker is designing experiments to find out if it does. He said he would be surprised if his group did not identify a similar mechanism in people, since such systems have been found in fruit flies, and the mouse visual system has so far proved to be a good model of many aspects of human vision.
“The sense of touch only tells you about objects that are close, and the auditory system is generally not as sensitive as the visual system to the exact position of objects,” he said. “It seems that it would be generally useful to have vision – the sensory modality that tells you the most about things that are far away – work better as you’re moving through the world.”
Stryker said that the neural system identified in the new work may have evolved to conserve energy, by allowing the brain to operate at less than peak efficiency in less demanding behavioral situations. “When you don’t need your visual system to be in a high-gain state, your brain may use a lot less energy in responding,” said Stryker. “A change in gain when you’re moving is ideally what you’d like to see – the neuron is doing the same thing that it’s always doing, but it’s talking louder to the rest of the brain.”
In the new research, mice were allowed to walk or run freely on a Styrofoam ball suspended on an air cushion while the scientists used a technique known as two-photon imaging to monitor the activation of cells in the primary visual area of the brain, known as V1.
The researchers found that a subset of V1 neurons, those that contain a substance called vasoactive intestinal peptide (VIP), were robustly activated in a time-locked fashion purely by locomotion, even in darkness, while other V1 neurons remained largely silent.
The mice were presented with visual stimuli both while motionless and while moving, and measurements showed that walking could increase the response of V1 neurons by more than 30 percent. Moreover, V1 responses to these stimuli increased or declined in tandem with the activity of VIP neurons, and with the starting or stopping of walking by the mice.
To firmly establish that VIP neurons were responsible for these changes, the researchers used optogenetic techniques, inserting light-sensitive proteins exclusively into VIP neurons. Using light to stimulate just this population of cells, the team found that they could emulate the effects of locomotion – when VIP cells were activated, V1 cells responded more strongly to stimuli, regardless of whether the animals were moving. Conversely, when the researchers specifically targeted and disabled VIP cells, locomotion-induced increases in the response of other V1 cells were abolished.
Scientists catch brain damage in the act
Scientists have uncovered how inflammation and lack of oxygen conspire to cause brain damage in conditions such as stroke and Alzheimer’s disease.
The discovery, published today in Neuron, brings researchers a step closer to finding potential targets to treat neurodegenerative disorders.
Chronic inflammation and hypoxia, or oxygen deficiency, are hallmarks of several brain diseases, but little was known about how they contribute to symptoms such as memory loss.
The study used state-of-the-art techniques that reveal the movements of microglia, the brain’s resident immune cells. Brain researcher Brian MacVicar had previously captured how they moved to areas of injury to repair brain damage.
The new study shows that the combination of inflammation and hypoxia activates microglia in a way that persistently weakens the connection between neurons. The phenomenon, known as long-term depression, has been shown to contribute to cognitive impairment in Alzheimer’s disease.
“This is a never-before-seen mechanism among three key players in the brain that interact together in neurodegenerative disorders,” says MacVicar with the Djavad Mowafaghian Centre for Brain Health at UBC and Vancouver Coastal Health Research Institute.
“Now we can use this knowledge to start identifying new potential targets for therapy.”
New contender for ‘fat gene’ found
Researchers may have been focusing on the wrong gene.
Scientists studying what they thought was a ‘fat gene’ seem to have been looking in the wrong place, according to research published today in Nature. It suggests instead that the real culprit is another gene that the suspected obesity gene interacts with.
In 2007, several genome studies identified mutations in a gene called FTO that were strongly associated with an increased risk of obesity and type 2 diabetes in humans. Subsequent studies in mice showed a link between the gene and body mass. So researchers, including Marcelo Nóbrega, a geneticist at the University of Chicago, thought that they had found a promising candidate for a gene that helped cause obesity.
The mutations were located in non-coding portions of FTO involved in regulating gene expression. But when Nóbrega looked closer, he found that something was amiss. These regulatory regions contained some elements that are specific for the lungs, one of the few tissues in which FTO is not expressed. “This made us pause,” he says. “Why are there regulatory elements that presumably regulate FTO in the tissue where it isn’t expressed?”
This was not the first red flag. Previous attempts to find a link between the presence of the obesity-associated mutations and the expression levels of FTO had been a “miserable failure”, he says. When Nóbrega presented his new results at meetings, he adds that many people came to him to say ‘I just knew there was something wrong here’.
So Nóbrega’s team cast the net wider, looking for genes in the broader neighbourhood of FTO whose expression matched that of the mutations, and found IRX3, a gene about half a million base pairs away. IRX3 encodes a transcription factor — a type of protein involved in regulating the expression of other genes — and is highly expressed in the brain, consistent with a role in regulating energy metabolism and eating behaviour.
When they examined the looping three-dimensional structure of the chromosome on which both genes sit in mice, zebrafish and human cells, they found that the obesity-associated regions in FTO were physically in contact with the promoter (the initial gene sequence which acts as an on/off switch) of IRX3. So the switches that turn on IRX3 are actually located far away from IRX3 itself, inside another gene. “We think of the genome as a linear thing, but it’s really a complex 3D structure that coils back onto itself,” he says.
Distant genes
IRX3 also appeared to be strongly linked with obesity. People with one of the obesity-associated mutations showed higher expression of IRX3, but not FTO, in brain tissue samples, the team found. Nóbrega and his colleagues also found that mice lacking the gene weighed 25–30% less than mice with a functional IRX3 gene; did not gain weight on a high-fat diet; were resistant to metabolic disorders such as diabetes and had more of the energy-burning cells known as brown fat. The same results were seen in mice in which the expression of IRX3 was blocked in the hypothalamus, a brain region known to regulate feeding behaviour and energy balance.
Inês Barroso, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, says that the work answers some of the questions around the biology of the link found in the genome-wide association studies (GWAS). “That’s always the tricky thing; a GWAS gives you an association, but it’s just a marker on the genome, it doesn’t actually say anything about which gene it’s affecting,” she says. “This strongly suggests that mediation of body mass is going to be through IRX3 rather than FTO.”
Nóbrega thinks geneticists should keep in mind this example of unexpected interactions between distant genes when dealing with genetic association studies. “There may be many other cases where people are studying the wrong gene,” he says. “We might be chasing ghosts.”
(Image caption: This image shows a PC12 cell growing onto a randomly textures surface. Note how the cell is spreading out in all directions.)
Surface Characteristics Influence Cellular Growth on Semiconductor Material
Changing the texture and surface characteristics of a semiconductor material at the nanoscale can influence the way that neural cells grow on the material.
The finding stems from a study performed by researchers at North Carolina State University, the University of North Carolina at Chapel Hill and Purdue University, and may have utility for developing future neural implants.
“We wanted to know how a material’s texture and structure can influence cell adhesion and differentiation,” says Lauren Bain, lead author of a paper describing the work and a Ph.D. student in the joint biomedical engineering program at NC State and UNC-Chapel Hill. “Basically, we wanted to know if changing the physical characteristics on the surface of a semiconductor could make it easier for an implant to be integrated into neural tissue – or soft tissue generally.”
The researchers worked with gallium nitride (GaN), because it is one of the most promising semiconductor materials for use in biomedical applications. They also worked with PC12 cells, which are model cells used to mimic the behavior of neurons in lab experiments.
In the study, the researchers grew PC12 cells on GaN squares with four different surface characteristics: some squares were smooth; some had parallel grooves (resembling an irregular corduroy pattern); some were randomly textured (resembling a nanoscale mountain range); and some were covered with nanowires (resembling a nanoscale bed of nails).
Very few PC12 cells adhered to the smooth surface. And those that did adhere grew normally, forming long, narrow extensions. More PC12 cells adhered to the squares with parallel grooves, and these cells also grew normally.
About the same number of PC12 cells adhered to the randomly textured squares as adhered to the parallel grooves. However, these cells did not grow normally. Instead of forming narrow extensions, the cells flattened and spread across the GaN surface in all directions.
More PC12 cells adhered to the nanowire squares than to any of the other surfaces, but only 50 percent of the cells grew normally. The other 50 percent spread in all directions, like the cells on the randomly textured surfaces.
“This tells us that the actual shape of the surface characteristics influences the behavior of the cells,” Bain says. “It’s a non-chemical way of influencing the interaction between the material and the body. That’s something we can explore as we continue working to develop new biomedical technologies.”
Nicotine Withdrawal Weakens Brain Connections Tied to Self-Control Over Cigarette Cravings
People who try to quit smoking often say that kicking the habit makes the voice inside telling them to light up even louder, but why people succumb to those cravings so often has never been fully understood. Now, a new brain imaging study in this week’s JAMA Psychiatry from scientists in Penn Medicine and the National Institute on Drug Abuse (NIDA) Intramural Research Program shows how smokers suffering from nicotine withdrawal may have more trouble shifting from a key brain network—known as default mode, when people are in a so-called “introspective” or “self-referential” state— and into a control network, the so-called executive control network, that could help exert more conscious, self-control over cravings and to focus on quitting for good.
The findings help validate a neurobiological basis behind why so many people trying to quit end up relapsing—up to 80 percent, depending on the type of treatment—and may lead to new ways to identify smokers at high risk for relapse who need more intensive smoking cessation therapy.
The brain imaging study was led by researchers at University of Pennsylvania’s new Brain and Behavior Change Program, led by Caryn Lerman, PhD, who is also the deputy director of Penn’s Abramson Cancer Center, and Elliot Stein, PhD, and collaborators at NIDA. They found that smokers who abstained from cigarettes showed weakened interconnectivity between certain large-scale networks in their brains: the default mode network, the executive control network, and the salience network. They posit that this weakened connectivity reduces smokers’ ability to shift into or maintain greater influence from the executive control network, which may ultimately help maintain their quitting attempt.
“What we believe this means is that smokers who just quit have a more difficult time shifting gears from inward thoughts about how they feel to an outward focus on the tasks at hand,” said Lerman, who also serves as the Mary W. Calkins professor in the Department of Psychiatry. “It’s very important for people who are trying to quit to be able to maintain activity within the control network— to be able to shift from thinking about yourself and your inner state to focus on your more immediate goals and plan.”
Prior studies have looked at the effects of nicotine on brain interconnectivity in the resting state, that is, in the absence of any specific goal directed activity. This is the first study, however, to compare resting brain connectivity in an abstinent state and when people are smoking as usual, and then relate those changes to symptoms of craving and mental performance.
For the study, researchers conducted brain scans on 37 healthy smokers (those who smoke more than 10 cigarettes a day) ages 19 to 61 using functional magnetic resonance imaging (fMRI) in two different sessions: 24 hours after biochemically confirmed abstinence and after smoking as usual.
Imaging showed a significantly weaker connectivity between the salience network and default mode network during abstinence, compared with their sated state. Also, weakened connectivity during abstinence was linked with increases in smoking urges, negative mood, and withdrawal symptoms, suggesting that this weaker internetwork connectivity may make it more difficult for people to quit.
Establishing the strength of the connectivity between these large-scale brain networks will be important in predicting people’s ability to quit and stay quit, the authors write. Also, such connectivity could serve as a clinical biomarker to identify smokers who are most likely to respond to a particular treatment.
“Symptoms of withdrawal are related to changes in smokers’ brains, as they adjust to being off of nicotine, and this study validates those experiences as having a biological basis,” said Lerman. “The next step will be to identify in advance those smokers who will have more difficultly quitting and target more intensive treatments, based on brain activity and network connectivity.”
(Source: uphs.upenn.edu)
How the brain recognizes familiar music
Research from McGill University reveals that the brain’s motor network helps people remember and recognize music that they have performed in the past better than music they have only heard. A recent study by Prof. Caroline Palmer of the Department of Psychology sheds new light on how humans perceive and produce sounds, and may pave the way for investigations into whether motor learning could improve or protect memory or cognitive impairment in aging populations. The research is published in the journal Cerebral Cortex.
“The memory benefit that comes from performing a melody rather than just listening to it, or saying a word out loud rather than just hearing or reading it, is known as the ’production effect’ on memory”, says Prof. Palmer, a Canada Research Chair in Cognitive Neuroscience of Performance. “Scientists have debated whether the production effect is due to motor memories, such as knowing the feel of a particular sequence of finger movements on piano keys, or simply due to strengthened auditory memories, such as knowing how the melody tones should sound. Our paper provides new evidence that motor memories play a role in improving listeners’ recognition of tones they have previously performed.”
For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG).
“We found that pianists were better at recognizing pitch changes in melodies they had performed earlier,” said the study’s first author, Brian Mathias, a McGill PhD student who conducted the work at the Lyon Neuroscience Research Centre in France with additional collaborators Drs. Barbara Tillmann and Fabien Perrin.
The team found that EEG measurements revealed larger changes in brain waves and increased motor activity for previously performed melodies than for heard melodies about 200 milliseconds after the wrong notes. This reveals that the brain quickly compares incoming auditory information with motor information stored in memory, allowing us to recognize whether a sound is familiar.
“This paper helps us understand ‘experiential learning’, or ‘learning by doing’, and offers pedagogical and clinical implications,” said Mathias, “The role of the motor system in recognizing music, and perhaps also speech, could inform education theory by providing strategies for memory enhancement for students and teachers.”
(Source: mcgill.ca)
Restoring Order in the Brain
Alzheimer’s disease is the most widespread degenerative neurological disorder in the world. Over five million Americans live with it, and one in three senior citizens will die with the disease or a similar form of dementia. While memory loss is a common symptom of Alzheimer’s, other behavioral manifestations — depression, loss of inhibition, delusions, agitation, anxiety, and aggression — can be even more challenging for victims and their families to live with.
Now Prof. Daniel Offen and Dr. Adi Shruster of Tel Aviv University’s Sackler School of Medicine have discovered that by reestablishing a population of new cells in the part of the brain associated with behavior, some symptoms of Alzheimer’s disease significantly decreased or were reversed altogether.
The research, published in the journal Behavioural Brain Research, was conducted on mouse models; it provides a promising target for Alzheimer’s symptoms in human beings as well.
"Until 15 years ago, the common belief was that you were born with a finite number of neurons. You would lose them as you aged or as the result of injury or disease," said Prof. Offen, who also serves as Chief Scientific Officer at BrainStorm, a biotech company at the forefront of innovative stem cell research. "We now know that stem cells can be used to regenerate areas of the brain."
Speeding up recovery
After introducing stem cells in brain tissue in the laboratory and seeing promising results, Prof. Offen leveraged the study to mice with Alzheimer’s disease-like symptoms. The gene (Wnt3a) was introduced in the part of the mouse brain that controls behavior, specifically fear and anxiety, in the hope that it would contribute to the formation of genes that produce new brain cells.
According to Prof. Offen, untreated Alzheimer’s mice would run heedlessly into an unfamiliar and dangerous area of their habitats instead of assessing potential threats, as healthy mice do. Once treated with the gene that increased new neuron population, however, the mice reverted to assessing their new surroundings first, as usual.
"Normal mice will recognize the danger and avoid it. Mice with the disease, just like human patients, lose their sense of space and reality," said Prof. Offen. "We first succeeded in showing that new neuronal cells were produced in the areas injected with the gene. Then we succeeded in showing diminished symptoms as a result of this neuron repopulation."
"The loss of inhibition is a cause of great embarrassment for most patients and relatives of patients with Alzheimer’s," said Prof. Offen. "Often, patients take off their pants in public, having no sense of their surroundings. We saw parallel behavior in animal models with Alzheimer’s."
Next: Memory
After concluding that increased stem cell production in a certain area of the brain had a positive effect on behavioral deficits of Alzheimer’s, Prof. Offen has moved to research into the area of the brain that controls memory. He and his team are currently exploring it in the laboratory and are confident that the results of the new study will be similar.
"Although there are many questions to answer before this research produces practical therapies, we are very optimistic about the results and feel this is a promising direction for Alzheimer’s research," said Prof. Offen.
(Source: aftau.org)
Substance in Humans is Effective Fighting Stroke Damage
A molecular substance that occurs naturally in humans and rats was found to “substantially reduce” brain damage after an acute stroke and contribute to a better recovery, according to a newly released animal study by researchers at Henry Ford Hospital.
The study, published online before print in Stroke, the journal of the American Heart Association, was the first ever to show that the peptide AcSDKP provides neurological protection when administered one to four hours after the onset of an ischemic stroke.
This type of stroke occurs when an artery to the brain is blocked by a blood clot, cutting off oxygen and killing brain tissue with crippling or fatal results.
“Stroke is a leading cause of death and disability worldwide,” said Li Zhang, M.D., a researcher at Henry Ford and lead author of the study. “Our data showed that treatment of acute stroke with AcSDKP alone or in combination with tPA substantially reduced neurovascular damage and improved neurological outcome.”
Commonly called a “clot-buster,” tPA, or tissue plasminogen activator, is the only FDA-approved treatment for acute stroke.
However, tPA must be given shortly after the onset of stroke to provide the best results. It also has the potential to cause a brain hemorrhage.
The Henry Ford study found that this narrow “therapeutic window” is extended for up to four hours after stroke and the therapeutic benefit of tPA is amplified when tPA is combined with AcSDKP. Further, the researchers discovered that AcSDKP alone is an effective treatment if given up to one hour after the brain attack.
The researchers tested the actions of both substances on laboratory rats in which acute stroke had been induced. It was already known that the peptide AcSDKP provides anti-inflammatory effects and helps protect the heart when used to treat a variety of cardiovascular diseases. The Henry Ford scientists reasoned that the peptide may have similar neurological benefits.
Significantly, they found that AcSDKP can readily cross the so-called “blood brain barrier” that blocks other neuroprotective substances.
A battery of behavioral tests was given to the lab rats both before and after stroke was induced to measure the effects of AcSDKP administered alone one hour after onset and combined with tPA four hours after stroke.
Besides finding that both methods “robustly” decreased neurological damage associated with stroke, they did so without increasing the incidence of brain hemorrhage or the formation of additional blood clots.
“With the increased use of clot-busting therapy in patients with acute stroke, both the safety and effectiveness of the combined treatment shown in our study should encourage the development of clinical trials of AcSDKP with tPA,” Dr. Zhang says.