Posts tagged science
Posts tagged science
For a fish to swim forward, the nerve cells, or neurons, in its brain and spine have to control the swishing movements of its tail with very close coordination. However, the posture of the tail, which determines swimming direction somewhat like a rudder, also needs to be fine-tuned by the brain’s activity. Using the innovative method of optogenetics, scientists from the Max Planck Institute of Neurobiology in Martinsried have now identified a group of only about 15 nerve cells which steer the movements of the tail fin. Movements of the human body are also controlled via nerve pathways in the same region of the brain, which may therefore use processing mechanisms similar to those in fish.
For a long time, neurobiologists have been trying to find out how neuronal networks control both animal and human behaviour. In this context, there is controversy as to whether the brain’s organisation is decentralised as opposed to modular. In decentralised organisation, the interaction of a large number of neurons produces a specific behaviour pattern. If this is the case, individual neurons cannot be assigned an exact function. On the other hand, if the brain has a modular structure, individual regions might possess certain competencies, each making a specific contribution to behaviour. These types of neuronal circuit modules could be combined in many ways and influence a broad range of different behavioural responses.
Switches in the fish brain?
Researchers in Herwig Baier’s Group at the Max Planck Institute of Neurobiology want to get to the bottom of the brain’s organisational structure with the aid of zebrafish larvae. A network known as the descending reticular formation is located in the brainstem of these animals. The neurons of that region are optimally suited for studying the organisation of the brain: the cells are in direct contact with motor neurons in the spinal cord of the fish and can thus directly influence tail movements. “The reticular formation is a like a ‘cockpit’ for the fish, and we asked ourselves whether there are individual ‘switches’ or ‘joysticks‘, which are used to control the movements of the tail”, is how Herwig Baier summarises this challenge.
In their search for these switches, the researchers concentrated on a small brain nucleus (nMLF) within the reticular formation. But how can the influence of individual nMLF neurons on tail movements be studied? It is only recently that such investigations even became a possibility. Using the new method of optogenetics, the activity of nerve cells can be influenced with light. Since a zebrafish larva – including its brain – is transparent, scientists can very accurately “switch on” small sets of genetically modified cells by exposing the larva to blue light. Consequently, tail movements that are induced in this way can be attributed to identified neurons.
Neurons and tillers
The first series of tests showed that the cells of the nMLF region seem to be involved in a variety of movements – from forward propulsion to rotational motion. A second experimental series using optogenetic stimulation, however, suggested that the cells control the deflection of the tail in particular. Are the nMLF cells thus part of a multifunctional centre or are they truly specialised to perform certain functions? To resolve this question, the neurobiologists performed another set of trials in which they very specifically removed small sets of nMLF cells from the circuit. “This experiment gave us our breakthrough”, recalls Tod Thiele, lead author of the now published study.
The results show that, while nMLF cells are active in many aspects of swimming, a subset of these neurons contribute to only one part of the movement: they determine swimming direction through the posture of the tail. Thus, this population of neurons in the nMLF region are more akin to a specialised module within a decentralised control system of the swimming apparatus. Herwig Baier explains it like this: “We can compare the whole setup with the propulsion of a motorboat”. The boat’s engine, which drives the propeller, determines the thrust, whereas the tiller steers the boat. It seems that the tasks in the brain are divided up in a very similar way.
Some time ago, Herwig Baier’s team discovered a small region in the hindbrain, which acts like an engine and propels the fish forwards. “With the nMLF cells, we have now also found the tiller in the fish brain”, says Herwig Baier. In the human brain, movements are also controlled by a multitude of nuclei in the reticular formation. The study therefore suggests that the allocation of tasks in our brain could be similar to that of the zebrafish.
Humans have developed sophisticated concepts like mass and gravity to explain a wide range of everyday phenomena, but scientists have remarkably little understanding of how such concepts are represented by the brain.
Using advanced neuroimaging techniques, Queen’s University researchers have revealed how the brain stores knowledge about an object’s weight – information critical to our ability to successfully grasp and interact with objects in our environment.
Jason Gallivan, a Banting postdoctoral fellow in the Department of Psychology, and Randy Flanagan, a professor in the Department of Psychology, used functional magnetic resonance imaging (fMRI) to uncover what regions of the human brain represent an object’s weight prior to lifting that object. They found that knowledge of object weight is stored in ventral visual cortex, a brain region previously thought to only represent those properties of an object that can be directly viewed such as its size, shape, location and texture.
“We are working on various projects to determine how the brain produces actions on the world,” explains Dr. Gallivan about the work he is undertaking at the Centre for Neuroscience Studies at Queen’s. “Simply looking at an object doesn’t provide the brain with information about how much that object weighs. Take for example a suitcase. There is often nothing about its visual appearance that informs you of whether it is packed with clothes or empty. Rather, this is information that must be derived through recent interactions with that object and stored in the brain so as to guide our movements the next time we must lift and interact with that object.”
According to previous research, the ventral visual cortex supports visual processing for perception and object recognition whereas the dorsal visual cortex supports visual processing for the control of action. However, this division of labour had only been tested for visually guided actions like reaching, which are directed towards objects, and not for actions involving the manipulation of objects, which requires access to stored knowledge about object properties.
“Because information about object weight is primarily important for the control of action, we thought that this information might only be stored in motor-related areas of the brain,” says Dr. Gallivan. “Surprisingly, however, we found that this non-visual information was also stored in ventral visual cortex. Presumably this allows for the weight of an object to become easily associated with its visual properties.”
In ongoing research, Drs. Gallivan and Flanagan are using transcranial magnetic stimulation (TMS) to temporarily disrupt targeted brain areas in order to assess their contribution to skilled object manipulation. By identifying which areas of the brain control certain motor skills, Drs. Gallivan and Flanagan’s research will be helpful in assessing patients with neurological impairments including stroke.
The work was funded by the Canadian Institutes of Health Research (CIHR). The research was recently published in Current Biology.
Researchers at UC San Francisco have discovered that endostatin, a protein that once aroused intense interest as a possible cancer treatment, plays a key role in the stable functioning of the nervous system.
A substance that occurs naturally in the body, endostatin potently blocks the formation of new blood vessels. In studies in mice in the late 1990s, endostatin treatment virtually eliminated cancer by shutting down the blood supply to tumors, but subsequent human clinical trials proved disappointing.
“It was a very big surprise” to find that endostatin, through some other mechanism, helps to maintain the proper workings of synapses, the sites where communication between nerve cells takes place, said Graeme W. Davis, PhD, Hertzstein Distinguished Professor of Medicine in the Department of Biochemistry and Biophysics at UCSF and senior author of the new study. “Endostatin was not on our radar.”
The findings were reported online July 24 in the journal Neuron.
Synapses are continually shaped and reshaped by experience, a phenomenon known as plasticity. But for those changes to be meaningful, said Davis, they must take place against a stable background, which paradoxically requires another form of change that he and colleagues call “homeostatic plasticity.” Just as we change our pace, slowing down or speeding up, to keep abreast of a running partner, neurons adjust aspects of their function at synapses to compensate for changes in their synaptic partners brought on by aging, illness, or other factors.
In an example of homeostatic plasticity, in the neuromuscular disease myasthenia gravis, as muscle cells become less responsive to the neurotransmitter acetylcholine, nerve cells ramp up their secretion of the neurotransmitter to keep the system in balance for as long as possible. Some researchers believe that in other disorders, including autism and schizophrenia, a failure in such homeostatic mechanisms keeps synapses from functioning properly.
In previous research Davis noticed that applying a toxin to a muscle cell in the fruit fly Drosophila melanogaster triggers homeostatic plasticity in the neuron that forms a synapse on that muscle cell: the neuron—which is called presynaptic, because it is “before” the synapse with the muscle cell—reliably releases more neurotransmitter, just as happens when muscle cells begin to malfunction in myasthenia gravis.
Davis has since built on this model of homeostatic plasticity by painstakingly knocking out Drosophila genes one by one and recording from presynaptic neurons to see which genes are necessary for the homeostatic response, because it is these genes that may be compromised in diseases affecting the process.
“So far we’ve tested about 1,000 genes this way, which has entailed close to 10,000 recordings,” Davis said.
Using this technique Davis and colleagues observed at one point that knocking out a gene called multiplexin significantly hampered homeostatic plasticity in presynaptic neurons. But because that gene helps to form a structural protein known as collagen—which in humans is a component of ligaments, tendons, and cartilage—the finding wasn’t immediately considered relevant to synaptic function.
The team learned that the multiplexin protein can be snipped by an enzyme to produce endostatin, so in experiments led by postdoctoral fellow Tingting Wang, PhD, they tested whether endostatin might play a role in homeostatic plasticity.
“Nobody picked up multiplexin to work on for a couple of years, because we didn’t think a collagen could be that interesting,” Davis said. “Then, when a new postdoc, Tingting Wang, came to the lab, we started thinking about it harder.”
When the group genetically deleted the portion of Drosophila multiplexin that forms endostatin, presynaptic neurons behaved normally, but homeostatic plasticity was severely compromised when toxin was applied to postsynaptic muscle cells. On the opposite side of the coin, when the team overexpressed endostatin at Drosophila synapses lacking multiplexin, homeostasis was restored, whether endostatin was expressed in muscle cells or presynaptic neurons.
The research team is unsure precisely how and where endostatin exerts its effects on homeostatic plasticity, but they believe that multiplexin is cleaved at the postsynaptic site to form endostatin, and that the endostatin signal is conveyed to the presynaptic neuron to alter its function. “Because so many people in the cancer world have studied endostatin, there is a great set of tools available” to study the protein, Davis said, so he expects his group to make rapid progress in addressing these questions.
“Despite its checkered history in cancer, we know endostatin is a signaling molecule and we know that the brain has a great deal of collagen—we just haven’t known what it does, and we certainly don’t know what endostatin’s receptors in the brain might be.” Davis said. “But it’s pretty exciting to think about a new signaling molecule with a profound role in the stabilization of the function of neural circuits.”
People choosing between two or more equally positive outcomes experience paradoxical feelings of pleasure and anxiety, feelings associated with activity in different regions of the brain, according to research led by Amitai Shenhav, an associate research scholar at the Princeton Neuroscience Institute at Princeton University.
In one experiment, 42 people rated the desirability of more than 300 products using an auction-like procedure. Then they looked at images of paired products with different or similar values and were asked to choose between them. Their brain activity was scanned using functional magnetic resonance imaging (fMRI). After the scan, participants reported their feelings before and during each choice. They received one of their choices at the end of the study.
Choices between two highly valued items (high-high), such as a digital camera and a camcorder, were associated with the most positive feelings and the greatest anxiety, compared with choices between items of low value (low-low), like a desk lamp and a water bottle, or between items of different values (low-high). Functional MRI scans showed activity in two regions of the brain, the striatum and the prefrontal cortex, both known to be involved in decision-making. Interestingly, lower parts of both regions were more active when subjects felt excited about being offered the choice, while activity in upper parts was strongly tied to feelings of anxiety.
This evidence that parallel brain circuits are associated with opposing emotional reactions helps to answer a puzzling question, according to Shenhav: “Why isn’t our positivity quelled by our anxiety, or our anxiety quelled by the fact that we’re getting this really good thing at the end? This suggests that it’s because these circuits evolved for two different reasons,” he said. “One of them is about evaluating the thing we’re going to get, and the other is about guiding our actions and working out how difficult the choice will be.”
The study, “Neural correlates of dueling affective reactions to win-win choices,” was published July 14 in the Proceedings of the National Academy of Sciences. Shenhav conducted the research as a graduate student at Harvard University, along with Professor of Psychology and Neuroscience Randy Buckner, the study’s senior author.
A second fMRI experiment showed that the same patterns of emotional reactions and brain activity persisted even when the participants were told before each choice how similarly they had valued the items. Their anxiety didn’t abate, despite knowing how little they stood to lose by making a “wrong” choice. In a third experiment, Shenhav and Buckner tested whether giving people more than two choices increased their levels of anxiety. Indeed, they found that providing six options led to higher levels of anxiety than two options, particularly when all six of the options were highly valued items. But positive feelings about being presented with the choice were similar for two or six options.
This suggests that the anxiety stems from the conflict of making the decision, rather than the opportunity cost of the choice — an economic concept that refers to the lost value of the second-best option. The opportunity cost should be the same, regardless of the number of choices. In addition, subjects in this final study were given an unlimited amount of time to make a decision, compared with 1.5 seconds in the first two studies. The results showed that time pressure was not the main source of anxiety during the choices.
At the end of each study, participants had a surprise opportunity to reverse their earlier choices. Higher activity in a part of the brain called the anterior cingulate cortex around the time of an initial choice predicted whether that decision would later be reversed. Previous work has shown that this brain region is involved in assessing how conflicted an individual feels over a particular choice; this result suggests that some choices may have continued to elicit conflict after the participant made a decision, Shenhav said. The researchers also found that people who reported more anxiety in their daily lives were more likely to change their minds.
This work could explain why ostensibly positive options can evoke a mixture of positive and negative responses, which are not explained by purely economic analyses of choice. “Rationally, there’s no reason why when you put one good thing with another good thing, you should feel worse about the situation,” said Brian Knutson, an associate professor of psychology and neuroscience at Stanford University, who is familiar with the work but was not involved in it. “The neuroimaging tells us that these different mechanisms are fighting with each other,” he said. “Understanding that dynamic can help us understand why decisions that we think should make us feel better can actually make us feel worse.”
According to Shenhav, this research could shed light on the neural processes that can make more momentous choices so paralyzing for some people — for instance, deciding where to go to college or which job offer to take. But he admits that even more trivial decisions can be tough for him. “I probably experience more win-win choice anxiety than the average person,” he said. “I’m even terrible at choosing where to eat dinner.”
The price of learning from rewarding choices may be just a touch of self-delusion, according to a new study in Neuron.
The research by Brown University brain scientists links a fundamental problem in neuroscience called “credit assignment” — how the brain reinforces learning only in the exact circuits that caused the rewarding choice — to an oft-observed quirk of behavior called “choice bias” – we value the rewards we choose more than equivalent rewards we don’t choose. The researchers used computational modeling and behavioral and genetic experiments to discover evidence that choice bias is essentially a byproduct of credit assignment.
“We weren’t looking to explain anything about choice bias to start off with,” said lead author Jeffrey Cockburn, a graduate student in the research group of senior author Michael Frank, associate professor of cognitive, linguistic, and psychological sciences. “This just happened to be the behavioral phenomenon we thought would emerge out of this credit assignment model.”
So the next time a friend raves about the movie he chose and is less enthusiastic about the just-as-good one that you chose, you might be able to chalk it up to his basic learning circuitry and a genetic difference that affects it.
The model, developed by Frank, Cockburn, and co-author Anne Collins, a postdoctoral researcher, was based on prior research on the function of the striatum, a part of the brain’s basal ganglia (BG) that is principally involved in representing reward values of actions and picking one. “An interaction between three key BG regions moderates that decision-making process. When a rewarding choice has been made, the substantia nigra pars compacta (SNc) releases dopamine into the striatum to reinforce connections between cortex and striatum, so that rewarded actions are more likely to be repeated. But how does the SNc reinforce just the circuits that made the right call? The authors proposed a mechanism by which another part of the subtantia nigra, the SNr, detects when actions are worth choosing and then simultaneously amplifies any dopamine signal coming from the SNc.”
“The novel part here is that we have proposed a mechanism by which the BG can detect when it has selected an action and should therefore amplify the dopamine reinforcing event specifically at that time,” Frank said. “When the SNr decides that striatal valuation signals are strong enough for one action, it releases the brakes not only on downstream structures that allow actions to be executed, but also on the SNc dopamine system, so any unexpected rewards are amplified.”
Specifically, dopamine provides reinforcement by enhancing the responsiveness of connections between cells so that a circuit can more easily repeat its rewarding behavior in the future. But along with that process of reinforcing the action of choosing, the value placed on the resulting reward becomes elevated compared to rewards not experienced this way.
That prediction seemed intriguing, but it still had to be tested. The authors identified both behavioral and genetic tests that would be telling.
They recruited 80 people at Brown and elsewhere in Providence to play a behavioral game and to donate some saliva for genetic testing.
The game first presented the subjects pictures of arbitrary Japanese characters that would have different probabilities of rewards if chosen ranging from a 20 percent to 80 percent chance of winning a point or losing a point. For some characters, the player could choose a character to discover its resulting reward or penalty, whereas for others, its result was simply given to them. After that learning phase, the subjects were then presented the characters in pairs and instructed to pick the one they thought had the highest chance of winning based on what they had learned.
The researchers built the game so that for every character a player could choose, there was an equally rewarding one that had merely been given to them. On average, players showed a clear choice bias in that they were more likely to prefer rewarding characters that they had chosen over equally rewarding characters they had been given.
Notably, they exhibited no choice bias between unrewarding characters suggesting that choice bias emerges only in relation to reward, one of the key predictions of their model. But they wanted to test further whether the impact of reward on choice bias was related to the proposed biological mechanism, that striatal dopaminergic learning is enhanced to chosen rewards.
The genetic tests focused on single-letter differences in a gene called DARPP-32, which governs how well cells in the striatum respond to the reinforcing influence of dopamine.
People with one version of the gene have been shown in previous research to be less able to learn from rewards, while people with other versions were less driven by reward in learning.
“The reason why this gene is interesting is because we know something about the biology of what it does and where it is expressed in the brain,” Frank said. “It’s predominant in the striatum and specifically affects synaptic plasticity induced by dopamine signaling. It’s related to the imbalance by which you learn from really good things or not so good things.
“The logic was if the mechanism that we think describes this choice bias and credit assignment problem is accurate then that gene should predict the impact of how good something was on this choice bias phenomenon,” he said.
Indeed, that’s what the data showed. People with the form of the gene that predisposed them to be responsive to big rewards also showed more choice bias from the most strongly rewarded characters. Interestingly, the other people also showed choice bias, but more strongly for those characters that were more mediocre. This pattern was mirrored by the authors’ model when it simulated the effects of DARPP-32 on reward learning imbalances from positive vs. negative outcomes.
For some people, the plums are sweeter if they picked them.
(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)
Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.
Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.
Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.
In the current study, a team led byfocused on the . These bind the neurotransmitter and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”
A pair of helpers
Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”
This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.
The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.
However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”
The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.
Fast sequence of signals
However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.
Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.
“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”
Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”
Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.
A research team led by Jackson Laboratory Professor and Howard Hughes Investigator Susan Ackerman, Ph.D., has pinpointed a surprising mechanism behind neurodegeneration in mice, one that involves a defect in a key component of the cellular machinery that makes proteins, known as transfer RNA or tRNA.
The researchers report in the journal Science that a mutation in a gene that produces tRNAs operating only in the central nervous system results in a “stalling” or pausing of the protein production process in the neuronal ribosomes. When another protein the researchers identified, GTPBP2, is also missing, neurodegeneration results.
“Our study demonstrates that individual tRNA genes can be tissue-specifically expressed in vertebrates,” Ackerman says, “and mutations in such genes may cause disease or modify other phenotypes. This is a new area to look for disease mechanisms.”
Neurodegeneration—the process through which mature neurons decay and ultimately die—is poorly understood, yet it underlies major human diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease).
While the causes of neurodegeneration are still coming to light, there is mounting evidence that neurons are exquisitely sensitive—much more so than other types of cells—to disruptions in how proteins are made and how they fold.
tRNAs are critical in translating the genetic code into proteins, the workhorses of the cell. tRNAs possess a characteristic cloverleaf shape with two distinct “business” ends—one that reads out the genetic code in three-letter increments (or triplets), and another that transports the protein building block specified by each triplet (known as an amino acid).
In higher organisms, tRNAs are strikingly diverse. For example, while there are 61 distinct triplets that are recognized by tRNAs in humans, the human genome contains roughly 500 tRNA genes. To date little is known about why they are so numerous, whether they carry out overlapping or redundant functions, or whether they possibly have roles beyond the making of proteins.
“Multiple genes encode almost all tRNA types,” Ackerman says. “In fact, AGA codons are decoded by five tRNAs in mice. Until now, this apparent redundancy has caused us to completely overlook the disease-causing potential of mutations in tRNAs, as well as other repetitive genes.”
Ackerman and her colleagues at The Jackson Laboratory in Bar Harbor, Maine, and Farmington, Conn., The Scripps Research Institute in LaJolla, Calif., and Kumamoto University in Japan pinpointed a mutation in the tRNA gene n-Tr20 as a genetic culprit behind the neurodegeneration observed in mice lacking GTPBP2.
Remarkably, the tRNA’s activity is confined to the brain and other parts of the central nervous system, in both mice and humans. The tRNA encoded by n-Tr20 recognizes the triplet code, AGA (which specifies the amino acid arginine).
The n-Tr20 defect disrupts how proteins are made. Specifically, it causes the “factories” responsible for synthesizing proteins, called ribosomes, to stall when they encounter an AGA triplet.
Such stalling can be largely overcome, thanks to the work of a partner protein called GTPBP2. But when this partner is missing—as it is in the mutant mice that Ackerman and her colleagues studied—the stalling intensifies. This is thought to be a driving force behind the neurodegeneration seen in these mice.
Neymar’s brain on auto-pilot
Brazilian superstar Neymar’s brain activity while dancing past opponents is less than 10 per cent the level of amateur players, suggesting he plays as if on auto-pilot, according to Japanese neurologists.
Results of brain scans conducted on Neymar indicate minimal cerebral function when he rotates his ankle and point to the Barcelona striker’s wizardry being uncannily natural.
"From MRI images, we discovered Neymar’s brain activity to be less than 10 per cent of an amateur player," researcher Eiichi Naito said on Friday.
"It is possible genetics is a factor, aided by the type of training he does."
The findings were published in the Swiss journal Frontiers in Human Neuroscience following a series of motor skills tests carried out on the 22-year-old Neymar and several other athletes in Barcelona in February.
(Image: Sergio Moraes / REUTERS)
Unlocking the secrets to better treating the pernicious disorders of obesity and dementia reside in the brain, according to a paper from American University’s Center for Behavioral Neuroscience. In the paper, researchers make the case for treating obesity with therapies aimed at areas of the brain responsible for memory and learning. Furthermore, treatments that focus on the hippocampus could play a role in reducing certain dementias.
"In the struggle to treat these diseases, therapies and preventive measures often fall short. This is a new way for providers who treat people with weight problems and for researchers who study dementias to think about obesity and cognitive decline," said Prof. Terry Davidson, center director and lead study author.
In the paper, published in the journal Physiology & Behavior, Davidson and colleague Ashley A. Martin review research findings linking obesity with cognitive decline, including the center’s findings about the “vicious cycle” model, which explains how weight-challenged individuals who suffer from particular kinds of cognitive impairment are more susceptible to overeating.
Obesity, Memory Deficits and Lasting Effects
It is widely accepted that overconsumption of dietary fats, sugar and sweeteners can cause obesity. These types of dietary factors are also linked to cognitive dysfunction. Foods that are risk factors for cognitive impairment (i.e., foods high in saturated fats and simple carbohydrates that make up the modern Western diet) are so widespread and readily available in today’s food environment, their consumption is all but encouraged, Davidson said.
Across age groups, evidence reveals links between excess food intake, body weight and cognitive dysfunction. Childhood obesity and consumption of the Western diet can have lasting effects, as seen through the normal aging process, cognitive deficits and brain pathologies. Several analyses of cases of mild cognitive impairment progressing to full-blown cases of Alzheimer’s disease show that the first signs of brain disease can occur at least 50 years prior to the emergence of serious cognitive dysfunction. These signs originate in the hippocampus, the area of the brain where memory, learning, decision making, behavior control and other cognitive functions come into play.
Still, most research on the role of the brain in obesity focuses on areas thought to be involved with hunger motivation (e.g., hypothalamus), taste (e.g., brain stem), reinforcement (e.g., striatum) and reward (e.g., nucleus accumbens) or with hormonal or metabolic disorders. This research has not yet been successful in generating therapies that are effective in treating or preventing obesity, Davidson says.
Experiments in rats by Davidson and colleagues show that overconsumption of the Western diet can damage or change the blood-brain barrier, the tight network of blood vessels protecting the brain and substrates for cognition. Certain kinds of dementias are known to arise from the breakdown in these brain substrates.
"Breakdown in the blood-brain barrier is more rationale for treating obesity as a learning and memory disorder," Davidson said. "Treating obesity successfully may also reduce the incidence of dementias, because the deterioration in the brain is often produced by the same diets that promote obesity."
The “vicious cycle” model AU researchers put forth says eating a Western diet high in saturated fats, sugar and simple carbohydrates produces pathologies in brain structures and circuits, ultimately changing brain pathways and disrupting cognitive abilities.
It works like this: People become less able to resist temptation when they encounter environmental cues (e.g., food itself or the sight of McDonald’s Golden Arches) that remind them of the pleasures of consumption. They then eat more of the same type of foods that produce the pathological changes in the brain, leading to progressive deterioration in those areas and impairments in cognitive processes important for providing control over one’s thoughts and behaviors. These cognitive impairments can weaken a person’s ability to resist thinking about food, making them more easily distracted by food cues in the environment and more susceptible to overeating and weight gain.
"People have known at least since the time of Hippocrates that one key to a healthy life is to eat in moderation. Yet many of us are unable to follow that good advice," Davidson said. "Our work suggests that new therapeutic interventions that target brain regions involved with learning and memory may lead to success in controlling both the urge to eat, as well as the undesirable consequences produced by overeating."
Lack of sleep, already considered a public health epidemic, can also lead to errors in memory, finds a new study by researchers at Michigan State University and the University of California, Irvine.
The study, published online in the journal Psychological Science, found participants deprived of a night’s sleep were more likely to flub the details of a simulated burglary they were shown in a series of images.
Distorted memory can have serious consequences in areas such as criminal justice, where eyewitness misidentifications are thought to be the leading cause of wrongful convictions in the United States.
“We found memory distortion is greater after sleep deprivation,” said Kimberly Fenn, MSU associate professor of psychology and co-investigator on the study. “And people are getting less sleep each night than they ever have.”
The Centers for Disease Control and Prevention calls insufficient sleep an epidemic and said it’s linked to vehicle crashes, industrial disasters and chronic diseases such as hypertension and diabetes.
The researchers conducted experiments at MSU and UC-Irvine to gauge the effect of insufficient sleep on memory. The results: Participants who were kept awake for 24 hours – and even those who got five or fewer hours of sleep – were more likely to mix up event details than participants who were well rested.
“People who repeatedly get low amounts of sleep every night could be more prone in the long run to develop these forms of memory distortion,” Fenn said. “It’s not just a full night of sleep deprivation that puts them at risk.”