Neuroscience

Articles and news from the latest research reports.

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How visual attention affects the brain

New work at the University of California, Davis, shows for the first time how visual attention affects activity in specific brain cells. The paper, published June 26 in the journal Nature, shows that attention increases the efficiency of signaling into the brain’s cerebral cortex and boosts the ratio of signal over noise.

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It’s the first time neuroscientists have been able to look at the behavior of synaptic circuits at such a fine-grained level of resolution while measuring the effects of attention, said Professor Ron Mangun, dean of social sciences at UC Davis and a researcher at the UC Davis Center for Mind and Brain.

Our brains recreate an internal map of the world we see through our eyes, mapping our visual field onto specific brain cells. Humans and our primate relatives have the ability to pay attention to objects in the visual scene without looking at them directly, Mangun said.

"Essentially, we ‘see out of the corner of our eyes,’ as the old saying goes. This ability helps us detect threats, and react quickly to avoid them, as when a car running a red light at high speed is approach from our side," he said.

Postdoctoral scholar Farran Briggs worked with Mangun and Professor Martin Usrey at the UC Davis Center for Neuroscience to measure signaling through single nerve connections, or synapses, in monkeys while they performed a standard cognitive test for attention: pressing a joystick in response to seeing a stimulus appear in their field of view.

By taking measurements on each side of a synapse leading into the cerebral cortex, the team could measure when neurons were firing, the strength of the signal and the signal-to-noise ratio.

The researchers found that when the animals were paying attention to an area within their field of view, the signal strength through corresponding synapses leading into the cortex became more effective, and the signal was boosted relative to background noise.

Combining established cognitive psychology with advanced neuroscience, the technique opens up new possibilities for research.

"There are a lot of questions about attention that we can now investigate, such as which brain mechanisms are disordered in diseases that affect attention," Usrey said.

The method could be used, for example, to probe the cholinergic nervous system, which is impacted by Alzheimer’s disease. It could also help to better understand developmental disorders that involve defects in attention, such as attention deficit hyperactivity disorder and autism.

"It’s going to turn out to be important for understanding and treating all kinds of diseases," Mangun predicted.

(Source: news.ucdavis.edu)

Filed under neuroimaging cerebral cortex neurons synapses visual attention psychology neuroscience science

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Blind(fold)ed by Science: Study Shows the Strategy Humans Use to Chase Objects

Vision and Hearing Work Together in the Brain to Help Us Catch a Moving Target

A new study has found that chasing down a moving object is not only a matter of sight or of sound, but of mind.

The study found that people who are blindfolded employ the same strategy to intercept a running ball carrier as people who can see, which suggests that multiple areas of the brain cooperate to accomplish the task.

Regardless of whether they could see or not, the study participants seemed to aim ahead of the ball carrier’s trajectory and then run to the spot where they expected him or her to be in the near future. Researchers call this a “constant target-heading angle” strategy, similar to strategies used by dogs catching Frisbees and baseball players catching fly balls.

It’s also the best way to catch an object that is trying to evade capture, explained Dennis Shaffer, assistant professor of psychology at The Ohio State University at Mansfield.

“The constant-angle strategy geometrically guarantees that you’ll reach your target, if your speed and the target’s speed stay constant, and you’re both moving in a straight line. It also gives you leeway to adjust if the target abruptly changes direction to evade you,” Shaffer said.

“The fact that people run after targets at a constant angle regardless of whether they can see or not suggests that there are brain mechanisms in place that we would call ‘polymodal’—areas of the brain that serve more than one form of sensory modality. Sight and hearing may be different senses, but within the brain the results of the sensory input for this task may be the same.”

The study appears in the journal Psychonomic Bulletin and Review.

Nine people participated in the study—mainly students at Ohio State and Arizona State University, where the study took place. Some had experience playing football, either at a high school or collegiate intramural level, while others had limited or no experience with football.

The nine of them donned motion-capture equipment and took turns in pairs, one running a football across a 20-meter field (nearly 22 yards), and one chasing. They randomly assigned participants to sighted and blindfolded conditions. In the blindfolded condition, participants wore a sleep mask and the runner carried a foam football with a beeping device inside, so that the chaser had a chance to locate them by sound. The runners ran in the general direction of the chasers at different angles, and sometimes the runner would cut right or left halfway through the run.

The study was designed so that the pursuer wouldn’t have time to consciously think about how to catch the runner.

“We were just focused on trying to touch the runner as soon as possible and before they exited the field,” Shaffer said. “The idea was to have the strategy emerge by instinct.”

About 97 percent of the time, the person doing the chasing used the constant-angle strategy—even when they were blindfolded and only able to hear the beeping football.

The results were surprising, even to Shaffer.

“I knew that this seemed to be a universal strategy across species, but I expected that people’s strategies would vary more when they were blindfolded, just because we aren’t used to running around blindfolded. I didn’t expect that the blindfolded strategies would so closely match the sighted ones.”

The findings suggest that there’s some common area in the brain that processes sight and sound together when we’re chasing something.

There is another strategy for catching moving targets. Researchers call it the pursuit or aiming strategy, because it involves speeding directly at the target’s current location. It’s how apex predators such as sharks catch prey.

“As long as you are much faster than your prey, the pursuit strategy is great. You just overtake them,” Shaffer said.

In a situation where the competition is more equal, the constant-angle strategy works better—the pursuer doesn’t have to be faster than the target, and if the target switches direction, the pursuer has time to adjust.

The study builds on Shaffer’s previous work with how collegiate-level football players chase ball carriers. He’s also studied how people catch baseballs and dogs catch Frisbees. All appear to use strategies similar to the constant target-heading angle strategy, which suggests that a common neural mechanism could be at work.

(Source: researchnews.osu.edu)

Filed under visual perception navigation motion perception psychology neuroscience science

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Tired and edgy? Sleep deprivation boosts anticipatory anxiety

UC Berkeley researchers have found that a lack of sleep, which is common in anxiety disorders, may play a key role in ramping up the brain regions that contribute to excessive worrying.

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Neuroscientists have found that sleep deprivation amplifies anticipatory anxiety by firing up the brain’s amygdala and insular cortex, regions associated with emotional processing. The resulting pattern mimics the abnormal neural activity seen in anxiety disorders. Furthermore, their research suggests that innate worriers – those who are naturally more anxious and therefore more likely to develop a full-blown anxiety disorder – are acutely vulnerable to the impact of insufficient sleep.

“These findings help us realize that those people who are anxious by nature are the same people who will suffer the greatest harm from sleep deprivation,” said Matthew Walker, a professor of psychology and neuroscience at UC Berkeley and senior author of the paper, which was published in the Journal of Neuroscience.

The results suggest that people suffering from such maladies as generalized anxiety disorder, panic attacks and post-traumatic stress disorder, may benefit substantially from sleep therapy. At UC Berkeley, psychologists such as Allison Harvey, a co-author on the Journal of Neuroscience paper, have been garnering encouraging results in studies that use sleep therapy on patients with depression, bipolar disorder and other mental illnesses.

“If sleep disruption is a key factor in anxiety disorders, as this study suggests, then it’s a potentially treatable target,” Walker said. “By restoring good quality sleep in people suffering from anxiety, we may be able to help ameliorate their excessive worry and disabling fearful expectations.”

While previous research has indicated that sleep disruption and psychiatric disorders often occur together, this latest study is the first to causally demonstrate that sleep loss triggers excessive anticipatory brain activity associated with anxiety, researchers said.

“It’s been hard to tease out whether sleep loss is simply a byproduct of anxiety, or whether sleep disruption causes anxiety,” said Andrea Goldstein, a UC Berkeley doctoral student in neuroscience and lead author of the study. “This study helps us understand that causal relationship more clearly.”

In their experiments, performed at UC Berkeley’s Sleep and Neuroimaging Laboratory, Walker and his research team scanned the brains of 18 healthy young adults as they viewed dozens of images, first after a good night’s rest, and again after a sleepless night. The images were either neutral, disturbing or alternated between both.

Participants in the experiments reported a wide range of baseline anxiety levels, but none fit the criteria for a clinical anxiety disorder. After getting a full night’s rest at the lab, which researchers monitored by measuring neural electrical activity, their brains were scanned via functional MRI as they waited to be shown, and then viewed 90 images during a 45-minute session.

To trigger anticipatory anxiety, researchers primed the participants using one of three visual cues prior to each series of images. A large red minus sign signaled to participants that they were about to see a highly unpleasant image, such as a death scene. A yellow circle portended a neutral image, such as a basket on a table. Perhaps most stressful was a white question mark, which indicated that either a grisly image or a bland, innocuous one was coming, and kept participants in a heightened state of suspense.

When sleep-deprived and waiting in suspenseful anticipation for a neutral or disturbing image to appear, activity in the emotional brain centers of all the participants soared, especially in the amygdala and the insular cortex. Notably, the amplifying impact of sleep deprivation was most dramatic for those people who were innately anxious to begin with.

“This discovery illustrates how important sleep is to our mental health,” said Walker. “It also emphasizes the intimate relationship between sleep and psychiatric disorders, both from a cause and a treatment perspective.”

(Source: newscenter.berkeley.edu)

Filed under sleep deprivation mental health insular cortex MRI anxiety disorders anxiety neuroscience psychology science

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Researchers Find Zinc’s Crucial Pathway to the Brain A new study helps explain how parts of the brain maintain their delicate balance of zinc, an element required in minute but crucial doses, particularly during embryonic development. The study, led at the Marine Biological Laboratory (MBL) by Mark Messerli in collaboration with scientists from the University of California, Davis, shows that neural cells require zinc uptake through a membrane transporter referred to as ZIP12. If that route is closed, neuronal sprouting and growth are significantly impaired and is fatal for a developing embryo. Their discovery was published in the Proceedings of the National Academy of Sciences. “This particular transporter is an essential doorway for many neurons in the central nervous system,” explains Messerli. “You knock out this one gene, this one particular pathway for the uptake of zinc into these cells, and you essentially prevent neuronal outgrowth. That’s lethal to the embryo.” Previously, scientists thought that zinc could use more than one pathway to enter the cell during early brain development. Some other elements, like calcium, enjoy such luxury of multiple options. Knocking out ZIP12, affected several critical processes in the brain, the scientists found. For example, frog embryos were unable to develop their neural systems properly. Additionally, neurons had trouble reaching out to connect to other neurons; their extensions were both shorter and fewer in number than normal. “We were surprised that ZIP12 was required at such an early and critical stage of development,” said Winyoo Chowanadisai, a researcher in nutrition at the University of California at Davis and visiting scientist in the Cellular Dynamics Program at the MBL. Dr. Chowanadisai was the first on the team to realize that ZIP12 is expressed in such abundance in the brain.“This study also reinforces the importance of periconceptional and prenatal nutrition and counseling to promote health during the earliest stages of life.” ZIP12 is part of a larger family of transporters involved in the movement of metal ions from outside the cell. Other reports showed that simultaneously blocking 3 other transporters in the family – including  ZIP1, 2, and 3 – had no major effects on embryonic development. Zinc is needed for healthy neural development, helping the brain to learn and remember new information. However, too much zinc can also be problematic. The research team is investigating the implications of their results on processes like embryonic brain development and wound healing. “[The result] was not expected,” said Messerli, a physiologist in the MBL’s Bell Center for Regenerative Biology and Tissue Enginering and Cellular Dynamics Program. ““We found that zinc uptake through ZIP12 is a regulatory point for neuronal growth, required for development and possibly required for learning and memory throughout life. We want to elucidate the downstream targets that zinc is affecting. That’s the next exploration.”

Researchers Find Zinc’s Crucial Pathway to the Brain

A new study helps explain how parts of the brain maintain their delicate balance of zinc, an element required in minute but crucial doses, particularly during embryonic development.

The study, led at the Marine Biological Laboratory (MBL) by Mark Messerli in collaboration with scientists from the University of California, Davis, shows that neural cells require zinc uptake through a membrane transporter referred to as ZIP12. If that route is closed, neuronal sprouting and growth are significantly impaired and is fatal for a developing embryo. Their discovery was published in the Proceedings of the National Academy of Sciences.

“This particular transporter is an essential doorway for many neurons in the central nervous system,” explains Messerli. “You knock out this one gene, this one particular pathway for the uptake of zinc into these cells, and you essentially prevent neuronal outgrowth. That’s lethal to the embryo.”

Previously, scientists thought that zinc could use more than one pathway to enter the cell during early brain development. Some other elements, like calcium, enjoy such luxury of multiple options.

Knocking out ZIP12, affected several critical processes in the brain, the scientists found. For example, frog embryos were unable to develop their neural systems properly. Additionally, neurons had trouble reaching out to connect to other neurons; their extensions were both shorter and fewer in number than normal.

“We were surprised that ZIP12 was required at such an early and critical stage of development,” said Winyoo Chowanadisai, a researcher in nutrition at the University of California at Davis and visiting scientist in the Cellular Dynamics Program at the MBL. Dr. Chowanadisai was the first on the team to realize that ZIP12 is expressed in such abundance in the brain.“This study also reinforces the importance of periconceptional and prenatal nutrition and counseling to promote health during the earliest stages of life.”

ZIP12 is part of a larger family of transporters involved in the movement of metal ions from outside the cell. Other reports showed that simultaneously blocking 3 other transporters in the family – including  ZIP1, 2, and 3 – had no major effects on embryonic development.

Zinc is needed for healthy neural development, helping the brain to learn and remember new information. However, too much zinc can also be problematic.

The research team is investigating the implications of their results on processes like embryonic brain development and wound healing.

“[The result] was not expected,” said Messerli, a physiologist in the MBL’s Bell Center for Regenerative Biology and Tissue Enginering and Cellular Dynamics Program. ““We found that zinc uptake through ZIP12 is a regulatory point for neuronal growth, required for development and possibly required for learning and memory throughout life. We want to elucidate the downstream targets that zinc is affecting. That’s the next exploration.”

Filed under brain development embryonic development neural cells zinc neuroscience science

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Alzheimer’s Disease Mouse Models Point To A Potential Therapeutic Approach Building on research published eight years ago in the journal Chemistry and Biology, Kenneth S. Kosik, Harriman Professor in Neuroscience and co-director of the Neuroscience Research Institute (NRI) at UC Santa Barbara, and his team have now applied their findings to two distinct, well-known mouse models, demonstrating a new potential target in the fight against Alzheimer’s and other neurodegenerative diseases. The results were published online June 4 as the Paper of the Week in the Journal of Biological Chemistry. As a Paper of the Week, Kosik’s work is among the top 2 percent of manuscripts the journal reviews in a year. Based on significance and overall importance, between 50 and 100 papers are selected for this honor from the more than 6,600 published each year. Kosik and his research team focused on tau, a protein normally present in the brain, which can develop into neurofibrillary tangles (NFTs) that, along with plaques containing amyloid-ß protein, characterize Alzheimer’s disease. When tau becomes pathological, many phosphate groups attach to it, causing it to become dysfunctional and intensely phosphorylated, or hyperphosphorylated. Aggregations of hyperphosphorylated tau are also referred to as paired helical filaments. "What struck me most while working on this project was how so many people I’d never met came to me to share their stories and personal anxieties about Alzheimer’s disease," said Xuemei Zhang, lead co-author and an assistant specialist in the Kosik Lab. "There is no doubt that finding therapeutic treatment is the only way to help this fast-growing population." Israel Hernandez, a postdoctoral scholar of the NRI and UCSB’s Department of Molecular, Cellular and Developmental Biology, is the paper’s other lead co-author. Treatments for hyperphosphorylated tau, one of the main causes of Alzheimer’s disease, do not exist. Current treatment is restricted to drugs that increase the concentration of neurotransmitters to promote signaling between neurons. However, this latest research explores the possibility that a small class of molecules called diaminothiazoles can act as inhibitors of kinase enzymes that phosphorylate tau. Kosik’s team studied the toxicity and immunoreactivity of several diaminothiazoles that targeted two key kinases, CDK5/p25 and GSK3ß, in two Alzheimer’s disease mouse models. The investigators found that the compounds can efficiently inhibit the enzymes with hardly any toxic effects in the therapeutic dose range. Treatment with the lead compound in this study, LDN-193594, dramatically affected the prominent neuronal cell loss that accompanies increased CDK5 activity. Diaminothiazole kinase inhibitors not only reduced tau phosphorylation but also exerted a neuroprotective effect in vivo. In addition to reducing the amount of the paired helical filaments in the mice’s brains, they also restored their learning and memory abilities during a fear-conditioning assay. According to the authors, the fact that treatment with diaminothiazole kinase inhibitors reduced the phosphorylation of tau provides strong evidence that small molecular kinase inhibitor treatment could slow the progression of tau pathology. “Given the contribution of both CDK5 and GSK3ß to tau phosphorylation,” said Kosik, “effective treatment of tauopathies may require dual kinase targeting.” Madison Cornwell, a Beckman Scholar with UCSB’s Center for Science and Engineering Partnerships who worked in Kosik’s lab, added: “As a beginning step, we demonstrated that two of these compounds were successful in clearing the brain of tau tangles in a mouse model, but someday inhibitors of these kinases may serve to ameliorate the symptoms of Alzheimer’s disease in patients.”

Alzheimer’s Disease Mouse Models Point To A Potential Therapeutic Approach

Building on research published eight years ago in the journal Chemistry and Biology, Kenneth S. Kosik, Harriman Professor in Neuroscience and co-director of the Neuroscience Research Institute (NRI) at UC Santa Barbara, and his team have now applied their findings to two distinct, well-known mouse models, demonstrating a new potential target in the fight against Alzheimer’s and other neurodegenerative diseases.

The results were published online June 4 as the Paper of the Week in the Journal of Biological Chemistry. As a Paper of the Week, Kosik’s work is among the top 2 percent of manuscripts the journal reviews in a year. Based on significance and overall importance, between 50 and 100 papers are selected for this honor from the more than 6,600 published each year.

Kosik and his research team focused on tau, a protein normally present in the brain, which can develop into neurofibrillary tangles (NFTs) that, along with plaques containing amyloid-ß protein, characterize Alzheimer’s disease. When tau becomes pathological, many phosphate groups attach to it, causing it to become dysfunctional and intensely phosphorylated, or hyperphosphorylated. Aggregations of hyperphosphorylated tau are also referred to as paired helical filaments.

"What struck me most while working on this project was how so many people I’d never met came to me to share their stories and personal anxieties about Alzheimer’s disease," said Xuemei Zhang, lead co-author and an assistant specialist in the Kosik Lab. "There is no doubt that finding therapeutic treatment is the only way to help this fast-growing population." Israel Hernandez, a postdoctoral scholar of the NRI and UCSB’s Department of Molecular, Cellular and Developmental Biology, is the paper’s other lead co-author.

Treatments for hyperphosphorylated tau, one of the main causes of Alzheimer’s disease, do not exist. Current treatment is restricted to drugs that increase the concentration of neurotransmitters to promote signaling between neurons.

However, this latest research explores the possibility that a small class of molecules called diaminothiazoles can act as inhibitors of kinase enzymes that phosphorylate tau. Kosik’s team studied the toxicity and immunoreactivity of several diaminothiazoles that targeted two key kinases, CDK5/p25 and GSK3ß, in two Alzheimer’s disease mouse models. The investigators found that the compounds can efficiently inhibit the enzymes with hardly any toxic effects in the therapeutic dose range.

Treatment with the lead compound in this study, LDN-193594, dramatically affected the prominent neuronal cell loss that accompanies increased CDK5 activity. Diaminothiazole kinase inhibitors not only reduced tau phosphorylation but also exerted a neuroprotective effect in vivo. In addition to reducing the amount of the paired helical filaments in the mice’s brains, they also restored their learning and memory abilities during a fear-conditioning assay.

According to the authors, the fact that treatment with diaminothiazole kinase inhibitors reduced the phosphorylation of tau provides strong evidence that small molecular kinase inhibitor treatment could slow the progression of tau pathology. “Given the contribution of both CDK5 and GSK3ß to tau phosphorylation,” said Kosik, “effective treatment of tauopathies may require dual kinase targeting.”

Madison Cornwell, a Beckman Scholar with UCSB’s Center for Science and Engineering Partnerships who worked in Kosik’s lab, added: “As a beginning step, we demonstrated that two of these compounds were successful in clearing the brain of tau tangles in a mouse model, but someday inhibitors of these kinases may serve to ameliorate the symptoms of Alzheimer’s disease in patients.”

Filed under alzheimer's disease beta amyloid dementia neurofibrillary tangles medicine neuroscience science

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Promising Alzheimer’s ‘drug’ halts memory loss A new class of experimental drug-like small molecules is showing great promise in targeting a brain enzyme to prevent early memory loss in Alzheimer’s disease, according to Northwestern Medicine® research. Developed in the laboratory of D. Martin Watterson, the molecules halted memory loss and fixed damaged communication among brain cells in a mouse model of Alzheimer’s. "This is the starting point for the development of a new class of drugs," said Watterson, lead author of a paper on the study and the John G. Searle Professor of Molecular Biology and Biochemistry at Northwestern University Feinberg School of Medicine. "It’s possible someday this class of drugs could be given early on to people to arrest certain aspects of Alzheimer’s." Changes in the brain start to occur ten to 15 years before serious memory problems become apparent in Alzheimer’s. "This class of drugs could be beneficial when the nerve cells are just beginning to become impaired," said Linda Van Eldik, a senior author of the paper and director of the University of Kentucky Sanders-Brown Center on Aging. The study is a collaboration between Northwestern’s Feinberg School, Columbia University Medical Center and the University of Kentucky. It will be published June 26 in the journal PLOS ONE. The novel drug-like molecule, called MW108, reduces the activity of an enzyme that is over-activated during Alzheimer’s and is considered a contributor to brain inflammation and impaired neuron function. Strong communication between neurons in the brain is an essential process for memory formation. "I’m not aware of any other drug that has this effect on the central nervous system," Watterson said. "These exciting results provide new hope for developing drugs against an important molecular target in the brain," said Roderick Corriveau, program director at the National Institute of Neurological Disorders and Stroke, which helped support the research. "They also provide a promising strategy for identifying small molecule drugs designed to treat Alzheimer’s disease and other neurological disorders." Watterson and his collaborators have a new National Institutes of Health (NIH) award to further refine the compound so it is metabolically stable and safe for use in humans and develop it to the point of starting a phase 1 clinical trial. (Image: Jay Vollmar)

Promising Alzheimer’s ‘drug’ halts memory loss

A new class of experimental drug-like small molecules is showing great promise in targeting a brain enzyme to prevent early memory loss in Alzheimer’s disease, according to Northwestern Medicine® research.

Developed in the laboratory of D. Martin Watterson, the molecules halted memory loss and fixed damaged communication among brain cells in a mouse model of Alzheimer’s.

"This is the starting point for the development of a new class of drugs," said Watterson, lead author of a paper on the study and the John G. Searle Professor of Molecular Biology and Biochemistry at Northwestern University Feinberg School of Medicine. "It’s possible someday this class of drugs could be given early on to people to arrest certain aspects of Alzheimer’s."

Changes in the brain start to occur ten to 15 years before serious memory problems become apparent in Alzheimer’s.

"This class of drugs could be beneficial when the nerve cells are just beginning to become impaired," said Linda Van Eldik, a senior author of the paper and director of the University of Kentucky Sanders-Brown Center on Aging.

The study is a collaboration between Northwestern’s Feinberg School, Columbia University Medical Center and the University of Kentucky. It will be published June 26 in the journal PLOS ONE.

The novel drug-like molecule, called MW108, reduces the activity of an enzyme that is over-activated during Alzheimer’s and is considered a contributor to brain inflammation and impaired neuron function. Strong communication between neurons in the brain is an essential process for memory formation.

"I’m not aware of any other drug that has this effect on the central nervous system," Watterson said.

"These exciting results provide new hope for developing drugs against an important molecular target in the brain," said Roderick Corriveau, program director at the National Institute of Neurological Disorders and Stroke, which helped support the research. "They also provide a promising strategy for identifying small molecule drugs designed to treat Alzheimer’s disease and other neurological disorders."

Watterson and his collaborators have a new National Institutes of Health (NIH) award to further refine the compound so it is metabolically stable and safe for use in humans and develop it to the point of starting a phase 1 clinical trial.

(Image: Jay Vollmar)

Filed under alzheimer's disease dementia memory memory formation brain inflammation neuroscience science

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Zebrafish study paves the way for new treatments for genetic disorder Scientists from the University of Sheffield have paved the way for new treatments for a common genetic disorder thanks to pioneering research on zebrafish – an animal capable of mending its own heart. Charcot Marie Tooth disease (CMT) is the most common genetic disorder affecting the nervous system. More than 20,000 people in the UK suffer from CMT, which typically causes progressive weakness and long-term pain in the feet, leading to walking difficulties. There is currently no cure for CMT. A research project conducted at the Sheffield Institute for Translational Neuroscience (SITraN) and the MRC Centre for Developmental and Biomedical Genetics (CDBG) by Dr Andrew Grierson and his team has revealed that zebrafish could hold the key to finding new therapeutic approaches to treat the condition. Dr Grierson said: “We have studied zebrafish with a genetic defect that causes CMT in humans. The fish develop normally, but once they reach adulthood they start to develop difficulties swimming. "By looking at the muscles of these fish we have discovered that the problem lies with the connections between motor neurons and muscle, which are known to be essential for walking in humans and also swimming in fish." CMT represents a group of neurodegenerative disorders typically characterised by demyelination (CMT1), a process which causes damage to the myelin sheaths that surround our neurons, or distal axon degeneration (CMT2) of motor and sensory neurons. The distal axon is the terminal where neurotransmitter packages within neurons are docked. The majority of CMT2 cases are caused by mutations in mitofusin 2 (MFN2), which is an essential gene encoding a protein responsible for fusion of the mitochondrial outer membrane. Mitochondria are known as the cellular power plants because they generate most of the supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. Dr Grierson said: “Previous work on this disorder using mammalian models such as mice has been problematic, because the mitofusin genes are essential for embryonic development. Using zebrafish we were able to develop a model with an adult onset, progressive phenotype with predominant symptoms of motor dysfunction similar to CMT2. "Motor neurons are the largest cells in our bodies, and as such they are highly dependent on a cellular transport system to deliver molecules through the long nerve cell processes which connect the spinal cord to our muscles. We already know that defects in the cellular transport system occur early in the development of diseases such as Alzheimer’s disease, Motor Neuron Disease and spastic paraplegia. Using our zebrafish model we have found that similar defects in transport are also a key part of the disease process in CMT." Dr Grierson and his team are now seeking funding to identify new treatments for CMT using the zebrafish model. Because of their size and unique biology, zebrafish are ideal to be used in drug screens for the identification of new therapies for untreatable human conditions. (Image courtesy: University College London)

Zebrafish study paves the way for new treatments for genetic disorder

Scientists from the University of Sheffield have paved the way for new treatments for a common genetic disorder thanks to pioneering research on zebrafish – an animal capable of mending its own heart.

Charcot Marie Tooth disease (CMT) is the most common genetic disorder affecting the nervous system. More than 20,000 people in the UK suffer from CMT, which typically causes progressive weakness and long-term pain in the feet, leading to walking difficulties. There is currently no cure for CMT.

A research project conducted at the Sheffield Institute for Translational Neuroscience (SITraN) and the MRC Centre for Developmental and Biomedical Genetics (CDBG) by Dr Andrew Grierson and his team has revealed that zebrafish could hold the key to finding new therapeutic approaches to treat the condition.

Dr Grierson said: “We have studied zebrafish with a genetic defect that causes CMT in humans. The fish develop normally, but once they reach adulthood they start to develop difficulties swimming.

"By looking at the muscles of these fish we have discovered that the problem lies with the connections between motor neurons and muscle, which are known to be essential for walking in humans and also swimming in fish."

CMT represents a group of neurodegenerative disorders typically characterised by demyelination (CMT1), a process which causes damage to the myelin sheaths that surround our neurons, or distal axon degeneration (CMT2) of motor and sensory neurons. The distal axon is the terminal where neurotransmitter packages within neurons are docked.

The majority of CMT2 cases are caused by mutations in mitofusin 2 (MFN2), which is an essential gene encoding a protein responsible for fusion of the mitochondrial outer membrane. Mitochondria are known as the cellular power plants because they generate most of the supply of adenosine triphosphate (ATP), which is used as a source of chemical energy.

Dr Grierson said: “Previous work on this disorder using mammalian models such as mice has been problematic, because the mitofusin genes are essential for embryonic development. Using zebrafish we were able to develop a model with an adult onset, progressive phenotype with predominant symptoms of motor dysfunction similar to CMT2.

"Motor neurons are the largest cells in our bodies, and as such they are highly dependent on a cellular transport system to deliver molecules through the long nerve cell processes which connect the spinal cord to our muscles. We already know that defects in the cellular transport system occur early in the development of diseases such as Alzheimer’s disease, Motor Neuron Disease and spastic paraplegia. Using our zebrafish model we have found that similar defects in transport are also a key part of the disease process in CMT."

Dr Grierson and his team are now seeking funding to identify new treatments for CMT using the zebrafish model. Because of their size and unique biology, zebrafish are ideal to be used in drug screens for the identification of new therapies for untreatable human conditions.

(Image courtesy: University College London)

Filed under zebrafish Charcot Marie Tooth disease genetic disorders nervous system demyelination medicine science

166 notes

A Deep Brain Disorder An SDSU research team has discovered that autism in children affects not only social abilities, but also a broad range of sensory and motor skills. A group of investigators from San Diego State University’s Brain Development Imaging Laboratory are shedding a new light on the effects of autism on the brain. The team has identified that connectivity between the thalamus, a deep brain structure crucial for sensory and motor functions, and the cerebral cortex, the brain’s outer layer, is impaired in children with autism spectrum disorders (ASD). Led by Aarti Nair, a student in the SDSU/UCSD Joint Doctoral Program in Clinical Psychology, the study is the first of its kind, combining functional and anatomical magnetic resonance imaging (fMRI) techniques and diffusion tensor imaging (DTI) to examine connections between the cerebral cortex and the thalamus. Nair and Dr. Ralph-Axel Müller, an SDSU professor of psychology who was senior investigator of the study, examined more than 50 children, both with autism and without. Brain communication The thalamus is a crucial brain structure for many functions, such as vision, hearing, movement control and attention. In the children with autism, the pathways connecting the cerebral cortex and thalamus were found to be affected, indicating that these two parts of the brain do not communicate well with each other. “This impaired connectivity suggests that autism is not simply a disorder of social and communicative abilities, but also affects a broad range of sensory and motor systems,” Müller said. Disturbances in the development of both the structure and function of the thalamus may play a role in the emergence of social and communicative impairments, which are among the most prominent and distressing symptoms of autism. While the findings reported in this study are novel, they are consistent with growing evidence on sensory and motor abnormalities in autism. They suggest that the diagnostic criteria for autism, which emphasize social and communicative impairment, may fail to consider the broad spectrum of problems children with autism experience. The study was supported with funding from the National Institutes of Health and additional funding from Autism Speaks Dennis Weatherstone Predoctoral Fellowship. It was published in the June issue of the journal, BRAIN.

A Deep Brain Disorder

An SDSU research team has discovered that autism in children affects not only social abilities, but also a broad range of sensory and motor skills.

A group of investigators from San Diego State University’s Brain Development Imaging Laboratory are shedding a new light on the effects of autism on the brain.

The team has identified that connectivity between the thalamus, a deep brain structure crucial for sensory and motor functions, and the cerebral cortex, the brain’s outer layer, is impaired in children with autism spectrum disorders (ASD).

Led by Aarti Nair, a student in the SDSU/UCSD Joint Doctoral Program in Clinical Psychology, the study is the first of its kind, combining functional and anatomical magnetic resonance imaging (fMRI) techniques and diffusion tensor imaging (DTI) to examine connections between the cerebral cortex and the thalamus.

Nair and Dr. Ralph-Axel Müller, an SDSU professor of psychology who was senior investigator of the study, examined more than 50 children, both with autism and without.

Brain communication

The thalamus is a crucial brain structure for many functions, such as vision, hearing, movement control and attention. In the children with autism, the pathways connecting the cerebral cortex and thalamus were found to be affected, indicating that these two parts of the brain do not communicate well with each other.

“This impaired connectivity suggests that autism is not simply a disorder of social and communicative abilities, but also affects a broad range of sensory and motor systems,” Müller said.

Disturbances in the development of both the structure and function of the thalamus may play a role in the emergence of social and communicative impairments, which are among the most prominent and distressing symptoms of autism.

While the findings reported in this study are novel, they are consistent with growing evidence on sensory and motor abnormalities in autism. They suggest that the diagnostic criteria for autism, which emphasize social and communicative impairment, may fail to consider the broad spectrum of problems children with autism experience.

The study was supported with funding from the National Institutes of Health and additional funding from Autism Speaks Dennis Weatherstone Predoctoral Fellowship. It was published in the June issue of the journal, BRAIN.

Filed under autism ASD cerebral cortex motor functions thalamus psychology neuroscience science

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Breastfeeding boosts ability to climb social ladder

Breastfeeding not only boosts children’s chances of climbing the social ladder, but it also reduces the chances of downwards mobility, suggests a large study published online in the Archives of Disease in Childhood.

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The findings are based on changes in the social class of two groups of individuals born in 1958 (17,419 people) and in 1970 (16,771 people).

The researchers asked each of the children’s mums, when their child was five or seven years old, whether they had breastfed him/her.

They then compared people’s social class as children - based on the social class of their father when they were 10 or 11 - with their social class as adults, measured when they were 33 or 34.

Social class was categorised on a four-point scale ranging from unskilled/semi-skilled manual to professional/managerial.

The research also took account of a wide range of other potentially influential factors, derived from regular follow-ups every few years. These included children’s brain (cognitive) development and stress scores, which were assessed using validated tests at the ages of 10-11.

Significantly fewer children were breastfed in 1970 than in 1958. More than two-thirds (68%) of mothers breastfed their children in 1958, compared with just over one in three (36%) in 1970.

Social mobility also changed over time, with those born in 1970 more likely to be upwardly mobile, and less likely to be downwardly mobile, than those born in 1958.

None the less, when background factors were accounted for, children who had been breastfed were consistently more likely to have climbed the social ladder than those who had not been breastfed. This was true of those born in both 1958 and 1970.

What’s more, the size of the “breastfeeding effect” was the same in both time periods. Breastfeeding increased the odds of upwards mobility by 24% and reduced the odds of downward mobility by around 20% for both groups.

Intellect and stress accounted for around a third (36%) of the total impact of breastfeeding: breastfeeding enhances brain development, which boosts intellect, which in turn increases upwards social mobility. Breastfed children also showed fewer signs of stress.

The evidence suggests that breastfeeding confers a range of long-term health, developmental, and behavioural advantages to children, which persist into adulthood, say the authors.

They note that it is difficult to pinpoint which affords the greatest benefit to the child - the nutrients found in breast milk or the skin to skin contact and associated bonding during breastfeeding.

“Perhaps the combination of physical contact and the most appropriate nutrients required for growth and brain development is implicated in the better neurocognitive and adult outcomes of breastfed infants,” they suggest.

Filed under breastfeeding social class brain development stress social mobility neuroscience psychology science

177 notes

Hunger affects decision making and perception of risk Hungry people are often difficult to deal with. A good meal can affect more than our mood, it can also influence our willingness to take risks. This phenomenon is also apparent across a very diverse range of species in the animal kingdom. Experiments conducted on the fruit fly, Drosophila, by scientists at the Max Planck Institute of Neurobiology in Martinsried have shown that hunger not only modifies behaviour, but also changes pathways in the brain. Animal behaviour is radically affected by the availability and amount of food. Studies prove that the willingness of many animals to take risks increases or declines depending on whether the animal is hungry or full. For example, a predator only hunts more dangerous prey when it is close to starvation. This behaviour has also been documented in humans in recent years: one study showed that hungry subjects took significantly more financial risks than their sated colleagues. Also the fruit fly, Drosophila, changes its behaviour depending on its nutritional state. The animals usually perceive even low quantities of carbon dioxide to be a sign of danger and opt to take flight. However, rotting fruit and plants – the flies’ main sources of food – also release carbon dioxide. Neurobiologists in Martinsried have now discovered how the brain deals with this constant conflict in deciding between a hazardous substance and a potential food source taking advantage of the fly as a great genetic model organism for circuit neuroscience. In various experiments, the scientists presented the flies with environments containing carbon dioxide or a mix of carbon dioxide and the smell of food. It emerged that hungry flies overcame their aversion to carbon dioxide significantly faster than fed flies – if there was a smell of food in the environment at the same time. Facing the prospect of food, hungry animals are therefore significantly more willing to take risks than sated flies. But how does the brain manage to decide between these options? Avoiding carbon dioxide is an innate behaviour and should therefore be generated outside the mushroom body in the fly’s brain: previously, the nerve cells in the mushroom body were linked only with learning and behaviour patterns that are based on learned associations. However, when the scientists temporarily disabled these nerve cells, hungry flies no longer showed any reaction whatsoever to carbon dioxide. The behaviour of fed flies, on the other hand, remained the same: they avoided the carbon dioxide. In further studies, the researchers identified a projection neuron which transports the carbon dioxide information to the mushroom body. This nerve cell is crucial in triggering a flight response in hungry, but not in fed animals. “In fed flies, nerve cells outside the mushroom body are enough for flies to flee from the carbon dioxide. In hungry animals, however, the nerve cells are in the mushroom body and the projection neuron, which carries the carbon dioxide information there, is essential for the flight response. If mushroom body or projection neuron activity is blocked, only hungry flies are no longer concerned about the carbon dioxide,” explains Ilona Grunwald-Kadow, who headed the study. The results show that the innate flight response to carbon dioxide in fruit flies is controlled by two parallel neural circuits, depending on how satiated the animals are. “If the fly is hungry, it will no longer rely on the ‘direct line’ but will use brain centres to gauge internal and external signals and reach a balanced decision,” explains Grunwald-Kadow. “It is fascinating to see the extent to which metabolic processes and hunger affect the processing systems in the brain,” she adds.

Hunger affects decision making and perception of risk

Hungry people are often difficult to deal with. A good meal can affect more than our mood, it can also influence our willingness to take risks. This phenomenon is also apparent across a very diverse range of species in the animal kingdom. Experiments conducted on the fruit fly, Drosophila, by scientists at the Max Planck Institute of Neurobiology in Martinsried have shown that hunger not only modifies behaviour, but also changes pathways in the brain.

Animal behaviour is radically affected by the availability and amount of food. Studies prove that the willingness of many animals to take risks increases or declines depending on whether the animal is hungry or full. For example, a predator only hunts more dangerous prey when it is close to starvation. This behaviour has also been documented in humans in recent years: one study showed that hungry subjects took significantly more financial risks than their sated colleagues.

Also the fruit fly, Drosophila, changes its behaviour depending on its nutritional state. The animals usually perceive even low quantities of carbon dioxide to be a sign of danger and opt to take flight. However, rotting fruit and plants – the flies’ main sources of food – also release carbon dioxide. Neurobiologists in Martinsried have now discovered how the brain deals with this constant conflict in deciding between a hazardous substance and a potential food source taking advantage of the fly as a great genetic model organism for circuit neuroscience.

In various experiments, the scientists presented the flies with environments containing carbon dioxide or a mix of carbon dioxide and the smell of food. It emerged that hungry flies overcame their aversion to carbon dioxide significantly faster than fed flies – if there was a smell of food in the environment at the same time. Facing the prospect of food, hungry animals are therefore significantly more willing to take risks than sated flies. But how does the brain manage to decide between these options?

Avoiding carbon dioxide is an innate behaviour and should therefore be generated outside the mushroom body in the fly’s brain: previously, the nerve cells in the mushroom body were linked only with learning and behaviour patterns that are based on learned associations. However, when the scientists temporarily disabled these nerve cells, hungry flies no longer showed any reaction whatsoever to carbon dioxide. The behaviour of fed flies, on the other hand, remained the same: they avoided the carbon dioxide.

In further studies, the researchers identified a projection neuron which transports the carbon dioxide information to the mushroom body. This nerve cell is crucial in triggering a flight response in hungry, but not in fed animals. “In fed flies, nerve cells outside the mushroom body are enough for flies to flee from the carbon dioxide. In hungry animals, however, the nerve cells are in the mushroom body and the projection neuron, which carries the carbon dioxide information there, is essential for the flight response. If mushroom body or projection neuron activity is blocked, only hungry flies are no longer concerned about the carbon dioxide,” explains Ilona Grunwald-Kadow, who headed the study.

The results show that the innate flight response to carbon dioxide in fruit flies is controlled by two parallel neural circuits, depending on how satiated the animals are. “If the fly is hungry, it will no longer rely on the ‘direct line’ but will use brain centres to gauge internal and external signals and reach a balanced decision,” explains Grunwald-Kadow. “It is fascinating to see the extent to which metabolic processes and hunger affect the processing systems in the brain,” she adds.

Filed under hunger fruit flies carbon dioxide neurons neural circuits starvation neuroscience science

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