Neuroscience

Articles and news from the latest research reports.

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Receptor may aid spread of Alzheimer’s and Parkinson’s in brain

Scientists at Washington University School of Medicine in St. Louis have found a way that corrupted, disease-causing proteins spread in the brain, potentially contributing to Alzheimer’s disease, Parkinson’s disease and other brain-damaging disorders.

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Image: An electron micrograph shows clumps of corrupted tau protein outside a nerve cell. Scientists have identified a receptor that lets these clumps into the cell, where the corruption can spread. Blocking this receptor with drugs may help treat Alzheimer’s, Parkinson’s and other disorders.

The research identifies a specific type of receptor and suggests that blocking it may aid treatment of theses illnesses. The receptors are called heparan sulfate proteoglycans (HSPGs).

“Many of the enzymes that create HSPGs or otherwise help them function are good targets for drug treatments,” said senior author Marc I. Diamond, MD, the David Clayson Professor of Neurology. “We ultimately should be able to hit these enzymes with drugs and potentially disrupt several neurodegenerative conditions.”

The study is available online in the Proceedings of the National Academy of Sciences.

Over the last decade, Diamond has gathered evidence that Alzheimer’s disease and other neurodegenerative diseases spread through the brain in a fashion similar to conditions such as mad cow disease, which are caused by misfolded proteins known as prions.

Proteins are long chains of amino acids that perform many basic biological functions. A protein’s abilities are partially determined by the way it folds into a 3-D shape. Prions are proteins that have become folded in a fashion that makes them harmful.

Prions spread across the brain by causing other copies of the same protein to misfold.

Among the most infamous prion diseases are mad cow disease, which rapidly destroys the brain in cows, and a similar, inherited condition in humans called Creutzfeldt-Jakob disease.

Diamond and his colleagues have shown that a part of nerve cells’ inner structure known as tau protein can misfold into a configuration called an amyloid. These corrupted versions of tau stick to each other in clumps within the cells. Like prions, the clumps spread from one cell to another, seeding further spread by causing copies of tau protein in the new cell to become amyloids.

In the new study, first author Brandon Holmes, an MD/PhD student, showed that HSPGs are essential for binding, internalizing and spreading clumps of tau. When he genetically disabled or chemically modified the HSPGs in cell cultures and in a mouse model, clumps of tau could not enter cells, thus inhibiting the spread of misfolded tau from cell to cell.

Holmes also found that HSPGs are essential for the cell-to-cell spread of corrupted forms of alpha-synuclein, a protein linked to Parkinson’s disease.

“This suggests that it may one day be possible to unify our understanding and treatment of two or more broad classes of neurodegenerative disease,” Diamond said. 

“We’re now sorting through about 15 genes to determine which are the most essential for HSPGs’ interaction with tau,” Holmes said. “That will tell us which proteins to target with new drug treatments.”

(Source: news.wustl.edu)

Filed under heparan sulfate proteoglycans receptors neurodegenerative diseases prions nerve cells neuroscience science

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First to measure the concerted activity of a neuronal circuit

Neurobiologists from the Friedrich Miescher Institute for Biomedical Research have been the first to measure the concerted activity of a neuronal circuit in the retina as it extracts information about a moving object. With their novel and powerful approach they can now not only visualize networks of neurons but can also measure functional aspects. These insights are direly needed for a better understanding of the processes in the brain in health and disease.

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For many decades electrophysiology and genetics have been the main tools in the toolbox of approaches to study individual neurons in the central nervous system to understand perception and behavior. In the last five years however, neurobiology has been riding a wave of technological advances that brought unprecedented insights: Optogenetics and genetically encoded activity sensors has allowed scientists to control and measure the activity of clearly defined neurons; the application of rabies viruses enabled the visualization of networks of interconnected nerve cells. What was still missing, was the link between neural circuit and monitoring of activity.

Scientists from the Friedrich Miescher Institute for Biomedical Research have now been the first to measure the concerted activity of a neuronal circuit in the retina as it extracts information about the movement of an object.

In a world defined through eyesight, it is crucial to be able to discern whether something moves towards us, moves away or moves next to us. It comes as no surprise then that in the retina several parallel neuronal circuits are reserved for the extraction of information about movement and that most of them are dedicated to the analysis of the direction of motion.

As they report online in Neuron, Keisuke Yonehara and Karl Farrow, two Postdoctoral Fellows in Botond Roska’s team at the FMI, have now been able to monitor the activity of all circuit elements in a motion sensitive retinal circuit at once, and pinpoint the site, at a subcellular level, where the information about the direction of the movement becomes encoded. To achieve this, they used genetically altered rabies viruses expressing calcium sensors developed by the laboratory of Klaus Conzelmann in Munich. The special property of rabies viruses is that they move across connected neurons and therefore are able to deliver the sensors to all circuit elements within a defined neuronal circuit. Simultaneous two-photon imaging allowed them then to monitor activity in every part of the neuronal circuit at once, even in subcellular compartments, such as axons, synapses and dendrites.

"We are extremely thrilled that with this new method, which combines the power of genetically altered rabies viruses with very powerful two-photon microscopy, we are now able to link circuit architecture with activity and ultimately function," comments Yonehara. "We have illustrated the power of the method for a better understanding of the perception of movement and are convinced that the method will allow us to reach a better understanding of many processes in the retina and in other parts of the brain."

(Source: medicalxpress.com)

Filed under optogenetics neural activity retina retinal circuit nerve cells neuroscience science

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Art preserves skills despite onset of vascular dementia in ‘remarkable’ case of a Canadian sculptor The ability to draw spontaneously as well as from memory may be preserved in the brains of artists long after the deleterious effects of vascular dementia have diminished their capacity to complete simple, everyday tasks, according to a new study by physicians at St. Michael’s Hospital. The finding, scheduled to be released today in the Canadian Journal of Neurological Sciences, looked at the last few years of the late Mary Hecht, an internationally renowned sculptor, who was able to draw spur-of-the moment and detailed sketches of faces and figures, including from memory, despite an advanced case of vascular dementia. "Art opens the mind," said Dr. Luis Fornazzari, neurological consultant at St. Michael’s Hospital’s Memory Clinic and lead author of the paper. "Mary Hecht was a remarkable example of how artistic abilities are preserved in spite of the degeneration of the brain and a loss in the more mundane, day-to-day memory functions." Hecht, who died in April 2013 at 81, had been diagnosed with vascular dementia and was wheelchair-bound due to previous strokes. Despite her vast knowledge of art and personal talent, she was unable to draw the correct time on a clock, name certain animals or remember any of the words she was asked to recall. But she quickly sketched an accurate portrait of a research student from the Memory Clinic. And she was able to draw a free-hand sketch of a lying Buddha figurine and reproduce it from memory a few minutes later. To the great delight of St. Michael’s doctors, Hecht also drew an accurate sketch of famed cellist Mstislav Rostropovich after she learned of his death earlier that day on the radio. While she was drawing and showing medical staff her own creations, Hecht spoke eloquently and without hesitation about art. "This is the most exceptional example of the degree of preservation of artistic skills we’ve seen in our clinic," said Dr. Corinne Fischer, director at St. Michael’s Hospital’s Memory Clinic and another of the paper’s authors. "As well, most of the other studies that have been done in this area looked at other kinds of dementia such as Alzheimer’s disease or frontal temporal dementia, while this is a case of cognitive reserve in a patient with fairly advanced vascular dementia." Dr. Fornazzari previously wrote a paper detailing a musician who, despite declining health because of Alzheimer’s disease, could still play the piano and learn new music. As well, in October 2011, Dr. Fischer and colleagues looked at bilingual patients with Alzheimer’s and discovered they had twice as much cognitive reserve as their unilingual counterparts. Educators should take a page from these results and encourage schools to teach the arts – whether sculpture, painting or music – rather than cutting back on them, said Dr. Fornazzari. “Art should be taught to everyone. It’s better than many medications and is as important as mathematics or history.” Both physicians want to lead a larger study of artists with neurological illnesses to further explore the importance of art and cognitive brain capacity.

Art preserves skills despite onset of vascular dementia in ‘remarkable’ case of a Canadian sculptor

The ability to draw spontaneously as well as from memory may be preserved in the brains of artists long after the deleterious effects of vascular dementia have diminished their capacity to complete simple, everyday tasks, according to a new study by physicians at St. Michael’s Hospital.

The finding, scheduled to be released today in the Canadian Journal of Neurological Sciences, looked at the last few years of the late Mary Hecht, an internationally renowned sculptor, who was able to draw spur-of-the moment and detailed sketches of faces and figures, including from memory, despite an advanced case of vascular dementia.

"Art opens the mind," said Dr. Luis Fornazzari, neurological consultant at St. Michael’s Hospital’s Memory Clinic and lead author of the paper. "Mary Hecht was a remarkable example of how artistic abilities are preserved in spite of the degeneration of the brain and a loss in the more mundane, day-to-day memory functions."

Hecht, who died in April 2013 at 81, had been diagnosed with vascular dementia and was wheelchair-bound due to previous strokes. Despite her vast knowledge of art and personal talent, she was unable to draw the correct time on a clock, name certain animals or remember any of the words she was asked to recall.

But she quickly sketched an accurate portrait of a research student from the Memory Clinic. And she was able to draw a free-hand sketch of a lying Buddha figurine and reproduce it from memory a few minutes later. To the great delight of St. Michael’s doctors, Hecht also drew an accurate sketch of famed cellist Mstislav Rostropovich after she learned of his death earlier that day on the radio.

While she was drawing and showing medical staff her own creations, Hecht spoke eloquently and without hesitation about art.

"This is the most exceptional example of the degree of preservation of artistic skills we’ve seen in our clinic," said Dr. Corinne Fischer, director at St. Michael’s Hospital’s Memory Clinic and another of the paper’s authors. "As well, most of the other studies that have been done in this area looked at other kinds of dementia such as Alzheimer’s disease or frontal temporal dementia, while this is a case of cognitive reserve in a patient with fairly advanced vascular dementia."

Dr. Fornazzari previously wrote a paper detailing a musician who, despite declining health because of Alzheimer’s disease, could still play the piano and learn new music. As well, in October 2011, Dr. Fischer and colleagues looked at bilingual patients with Alzheimer’s and discovered they had twice as much cognitive reserve as their unilingual counterparts.

Educators should take a page from these results and encourage schools to teach the arts – whether sculpture, painting or music – rather than cutting back on them, said Dr. Fornazzari. “Art should be taught to everyone. It’s better than many medications and is as important as mathematics or history.”

Both physicians want to lead a larger study of artists with neurological illnesses to further explore the importance of art and cognitive brain capacity.

Filed under vascular dementia memory art neurodegenerative diseases Mary Hecht neuroscience science

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Brain size may signal risk of developing an eating disorder

New research indicates that teens with anorexia nervosa have bigger brains than teens that do not have the eating disorder. That is according to a study by researchers at the University of Colorado’s School of Medicine that examined a group of adolescents with anorexia nervosa and a group without. They found that girls with anorexia nervosa had a larger insula, a part of the brain that is active when we taste food, and a larger orbitofrontal cortex, a part of the brain that tells a person when to stop eating.

Guido Frank, MD, assistant professor of psychiatry and neuroscience at CU School of Medicine, and his colleagues report that the bigger brain may be the reason people with anorexia are able to starve themselves. Similar results in children with anorexia nervosa and in adults who had recovered from the disease, raise the possibility that insula and orbitofrontal cortex brain size could predispose a person to develop eating disorders.

"While eating disorders are often triggered by the environment, there are most likely biological mechanisms that have to come together for an individual to develop an eating disorder such as anorexia nervosa," Frank says.

The researchers recruited 19 adolescent girls with anorexia nervosa and 22 in a control group and used magnetic resonance imaging (MRI) to study brain volumes. Individuals with anorexia nervosa showed greater left orbitofrontal, right insular, and bilateral temporal cortex gray matter compared to the control group. In individuals with anorexia nervosa, orbitofrontal gray matter volume related negatively with sweet tastes. An additional comparison of this study group with adults with anorexia nervosa and a healthy control group supported greater orbitofrontal cortex and insula volumes in the disorder across this age group as well.

The medial orbitofrontal cortex has been associated with signaling when we feel satiated by a certain type of food (so called “sensory specific satiety”). This study suggests that larger volume in this brain area could be a trait across eating disorders that promotes these individuals to stop eating faster than in healthy individuals, before eating enough.

The right insula is a region that processes taste, as well as integrates body perception and this could contribute to the perception of being fat despite being underweight.

This study is complementary to another that found adults with anorexia and individuals who had recovered from this illness also had differences in brain size, previously published in the American Journal of Psychiatry.

(Source: eurekalert.org)

Filed under eating disorders anorexia nervosa brain size orbitofrontal cortex adolescents

255 notes

Human Brains Are Hardwired for Empathy, Friendship, Study Shows Perhaps one of the most defining features of humanity is our capacity for empathy – the ability to put ourselves in others’ shoes. A new University of Virginia study strongly suggests that we are hardwired to empathize because we closely associate people who are close to us – friends, spouses, lovers – with our very selves. “With familiarity, other people become part of ourselves,” said James Coan, a U.Va. psychology professor in the College of Arts & Sciences who used functional magnetic resonance imaging brain scans to find that people closely correlate people to whom they are attached to themselves. The study appears in the August issue of the journal Social Cognitive and Affective Neuroscience. “Our self comes to include the people we feel close to,” Coan said. In other words, our self-identity is largely based on whom we know and empathize with. Coan and his U.Va. colleagues conducted the study with 22 young adult participants who underwent fMRI scans of their brains during experiments to monitor brain activity while under threat of receiving mild electrical shocks to themselves or to a friend or stranger. The researchers found, as they expected, that regions of the brain responsible for threat response – the anterior insula, putamen and supramarginal gyrus – became active under threat of shock to the self. In the case of threat of shock to a stranger, the brain in those regions displayed little activity. However when the threat of shock was to a friend, the brain activity of the participant became essentially identical to the activity displayed under threat to the self. “The correlation between self and friend was remarkably similar,” Coan said. “The finding shows the brain’s remarkable capacity to model self to others; that people close to us become a part of ourselves, and that is not just metaphor or poetry, it’s very real. Literally we are under threat when a friend is under threat. But not so when a stranger is under threat.” Coan said this likely is because humans need to have friends and allies who they can side with and see as being the same as themselves. And as people spend more time together, they become more similar. “It’s essentially a breakdown of self and other; our self comes to include the people we become close to,” Coan said. “If a friend is under threat, it becomes the same as if we ourselves are under threat. We can understand the pain or difficulty they may be going through in the same way we understand our own pain.” This likely is the source of empathy, and part of the evolutionary process, Coan reasons. “A threat to ourselves is a threat to our resources,” he said. “Threats can take things away from us. But when we develop friendships, people we can trust and rely on who in essence become we, then our resources are expanded, we gain. Your goal becomes my goal. It’s a part of our survivability.” People need friends, Coan added, like “one hand needs another to clap.”

Human Brains Are Hardwired for Empathy, Friendship, Study Shows

Perhaps one of the most defining features of humanity is our capacity for empathy – the ability to put ourselves in others’ shoes. A new University of Virginia study strongly suggests that we are hardwired to empathize because we closely associate people who are close to us – friends, spouses, lovers – with our very selves.

“With familiarity, other people become part of ourselves,” said James Coan, a U.Va. psychology professor in the College of Arts & Sciences who used functional magnetic resonance imaging brain scans to find that people closely correlate people to whom they are attached to themselves. The study appears in the August issue of the journal Social Cognitive and Affective Neuroscience.

“Our self comes to include the people we feel close to,” Coan said.

In other words, our self-identity is largely based on whom we know and empathize with.

Coan and his U.Va. colleagues conducted the study with 22 young adult participants who underwent fMRI scans of their brains during experiments to monitor brain activity while under threat of receiving mild electrical shocks to themselves or to a friend or stranger.

The researchers found, as they expected, that regions of the brain responsible for threat response – the anterior insula, putamen and supramarginal gyrus – became active under threat of shock to the self. In the case of threat of shock to a stranger, the brain in those regions displayed little activity. However when the threat of shock was to a friend, the brain activity of the participant became essentially identical to the activity displayed under threat to the self.

“The correlation between self and friend was remarkably similar,” Coan said. “The finding shows the brain’s remarkable capacity to model self to others; that people close to us become a part of ourselves, and that is not just metaphor or poetry, it’s very real. Literally we are under threat when a friend is under threat. But not so when a stranger is under threat.”

Coan said this likely is because humans need to have friends and allies who they can side with and see as being the same as themselves. And as people spend more time together, they become more similar.

“It’s essentially a breakdown of self and other; our self comes to include the people we become close to,” Coan said. “If a friend is under threat, it becomes the same as if we ourselves are under threat. We can understand the pain or difficulty they may be going through in the same way we understand our own pain.”

This likely is the source of empathy, and part of the evolutionary process, Coan reasons.

“A threat to ourselves is a threat to our resources,” he said. “Threats can take things away from us. But when we develop friendships, people we can trust and rely on who in essence become we, then our resources are expanded, we gain. Your goal becomes my goal. It’s a part of our survivability.”

People need friends, Coan added, like “one hand needs another to clap.”

Filed under empathy social cognition brain activity interpersonal relationships psychology neuroscience science

49 notes

The Bitter and the Sweet: Fruit Flies Reveal a New Interaction Between the Two Fruit flies have a lot to teach us about the complexity of food. Like these tiny little creatures, most animals are attracted to sugar but are deterred from eating it when bitter compounds are added. A new study conducted by UC Santa Barbara’s Craig Montell, Duggan Professor of Neuroscience in the Department of Molecular, Cellular and Developmental Biology, explains a breakthrough in understanding how sensory input impacts fruit flies’ decisions about sweet taste. The findings were published today in the journal Neuron. It is generally well known that the addition of bitter compounds inhibits attraction to sugars. However, until now the cellular and molecular mechanisms underlying an important aspect of this ubiquitous animal behavior were poorly understood. When animals encounter bitterness in foods, two factors cause them to stop eating. First, bitter compounds bind to proteins called bitter gustatory receptors (GRs), which inhibits feeding. The second –– and more elusive –– factor involves inhibition of the sugar response. This is the focus of Montell’s research. At the center of the team’s discovery is the function of an odorant-binding protein (OPB) in the gustatory system. These proteins are usually but not exclusively resident in the olfactory system. Montell’s team found definitive evidence that an OBP, synthesized and released from non-neuronal cells, not only binds bitter tastants, but also moves and binds to the surface of nearby gustatory receptor neurons (GRNs) that contain sugar-activated GRs. This unanticipated process inhibits the activity of these GRNs and reduces the fruit flies’ attraction to sugars. These results not only reveal an unexpected role for an OBP in taste, but also identify the first molecular player (OBP49a) involved in the integration of opposing attractive and aversive gustatory stimuli in fruit flies. The researchers used two different fruit flies, wild-type and mutants missing the OBP49a protein, to demonstrate that bitter compounds suppress feeding behavior by binding to the OBP49a protein. As expected, wild-type flies find bitter aversive and prefer the lower concentration of sucrose when the higher concentration of sucrose is laced with bitter tastants such as quinine. The same was not true of the mutant flies, which do not express OBP49a. Their avoidance behavior was impaired because the bitter compounds did not inhibit the sweet response by binding to OPB49. However, loss of OBP49a did not affect gustatory behavior or action potentials in sugar- or bitter-activated GRNs when the GRNs were presented with just one type of tastant. "We showed that the OBP49a protein was in very close proximity or even touching the sugar GRs," said Montell. "If the bitter compound weren’t present, there would be normal sugar activation. We found that decreased behavioral avoidance to a sucrose/aversive mixture in the mutant flies was due to a deficit in the sugar-activated GRNs and not due to effects on GRNs activated by bitter compounds." OBP49a is the first molecule shown to promote the inhibition of the sucrose-activated GRNs by aversive chemicals in fruit flies. The findings demonstrate at least one important cellular mechanism through which bitter and sweet taste integration occurs in the taste receptor neurons. However, the findings do not exclude the possibility that suppression of sweet by bitter compounds could also take place through the integration of separate bitter and sweet inputs in the brain. "As we get a better understanding of aversive and attractive chemosensory behaviors in flies, it helps us understand how insect pests can be controlled," said Montell. "This is a step toward understanding the behaviors of related insects that spread disease. Molecules related to the OBPs and GRs in fruit flies are also in ticks and mosquitos that spread parasites and viruses."

The Bitter and the Sweet: Fruit Flies Reveal a New Interaction Between the Two

Fruit flies have a lot to teach us about the complexity of food. Like these tiny little creatures, most animals are attracted to sugar but are deterred from eating it when bitter compounds are added.

A new study conducted by UC Santa Barbara’s Craig Montell, Duggan Professor of Neuroscience in the Department of Molecular, Cellular and Developmental Biology, explains a breakthrough in understanding how sensory input impacts fruit flies’ decisions about sweet taste. The findings were published today in the journal Neuron.

It is generally well known that the addition of bitter compounds inhibits attraction to sugars. However, until now the cellular and molecular mechanisms underlying an important aspect of this ubiquitous animal behavior were poorly understood.

When animals encounter bitterness in foods, two factors cause them to stop eating. First, bitter compounds bind to proteins called bitter gustatory receptors (GRs), which inhibits feeding. The second –– and more elusive –– factor involves inhibition of the sugar response. This is the focus of Montell’s research.

At the center of the team’s discovery is the function of an odorant-binding protein (OPB) in the gustatory system. These proteins are usually but not exclusively resident in the olfactory system. Montell’s team found definitive evidence that an OBP, synthesized and released from non-neuronal cells, not only binds bitter tastants, but also moves and binds to the surface of nearby gustatory receptor neurons (GRNs) that contain sugar-activated GRs.

This unanticipated process inhibits the activity of these GRNs and reduces the fruit flies’ attraction to sugars. These results not only reveal an unexpected role for an OBP in taste, but also identify the first molecular player (OBP49a) involved in the integration of opposing attractive and aversive gustatory stimuli in fruit flies.

The researchers used two different fruit flies, wild-type and mutants missing the OBP49a protein, to demonstrate that bitter compounds suppress feeding behavior by binding to the OBP49a protein. As expected, wild-type flies find bitter aversive and prefer the lower concentration of sucrose when the higher concentration of sucrose is laced with bitter tastants such as quinine.

The same was not true of the mutant flies, which do not express OBP49a. Their avoidance behavior was impaired because the bitter compounds did not inhibit the sweet response by binding to OPB49. However, loss of OBP49a did not affect gustatory behavior or action potentials in sugar- or bitter-activated GRNs when the GRNs were presented with just one type of tastant.

"We showed that the OBP49a protein was in very close proximity or even touching the sugar GRs," said Montell. "If the bitter compound weren’t present, there would be normal sugar activation. We found that decreased behavioral avoidance to a sucrose/aversive mixture in the mutant flies was due to a deficit in the sugar-activated GRNs and not due to effects on GRNs activated by bitter compounds."

OBP49a is the first molecule shown to promote the inhibition of the sucrose-activated GRNs by aversive chemicals in fruit flies. The findings demonstrate at least one important cellular mechanism through which bitter and sweet taste integration occurs in the taste receptor neurons. However, the findings do not exclude the possibility that suppression of sweet by bitter compounds could also take place through the integration of separate bitter and sweet inputs in the brain.

"As we get a better understanding of aversive and attractive chemosensory behaviors in flies, it helps us understand how insect pests can be controlled," said Montell. "This is a step toward understanding the behaviors of related insects that spread disease. Molecules related to the OBPs and GRs in fruit flies are also in ticks and mosquitos that spread parasites and viruses."

Filed under gustatory receptors fruit flies taste odorant-binding protein neuroscience science

317 notes

Brain circuit can tune anxiety New findings may help neuroscientists pinpoint better targets for antianxiety treatments. Anxiety disorders, which include posttraumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects. To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory. “The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says. In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels. Lead authors of the paper, which appears in the Aug. 21 issue of Neuron, are technical assistant Ada Felix-Ortiz and postdoc Anna Beyeler. Other authors are former research assistant Changwoo Seo, summer student Christopher Leppla and research scientist Craig Wildes. Measuring anxietyBoth the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact. To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus. The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges. When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges. Complex interactions In a study published in 2011, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs. “Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have totally opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.” The Neuron study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets, says Joshua Gordon, an associate professor of psychiatry at Columbia University. “The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection — synaptic proteins or ion channels, for example — that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon, who was not part of the research team. In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.

Brain circuit can tune anxiety

New findings may help neuroscientists pinpoint better targets for antianxiety treatments.

Anxiety disorders, which include posttraumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.

To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.

“The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says.

In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels.

Lead authors of the paper, which appears in the Aug. 21 issue of Neuron, are technical assistant Ada Felix-Ortiz and postdoc Anna Beyeler. Other authors are former research assistant Changwoo Seo, summer student Christopher Leppla and research scientist Craig Wildes.

Measuring anxiety

Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.

To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus.

The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.

When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges.

Complex interactions

In a study published in 2011, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs.

“Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have totally opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.”

The Neuron study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets, says Joshua Gordon, an associate professor of psychiatry at Columbia University.

“The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection — synaptic proteins or ion channels, for example — that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon, who was not part of the research team.

In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.

Filed under amygdala anxiety hippocampus PTSD mental health psychology neuroscience science

173 notes

Mood is Influenced by Immune Cells Called to the Brain in Response to Stress

New research shows that in a dynamic mind-body interaction during the interpretation of prolonged stress, cells from the immune system are recruited to the brain and promote symptoms of anxiety.

The findings, in a mouse model, offer a new explanation of how stress can lead to mood disorders and identify a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders.

The Ohio State University research also reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery – the rest of the body – and back to the central nervous system that ultimately influences behavior.

Unlike an infection, trauma or other problems that attract immune cells to the site of trouble in the body, this recruitment of monocytes that can promote inflammation doesn’t damage the brain’s tissue – but it does lead to symptoms of anxiety.

The research showed that the brain under prolonged stress sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.

In experiments conducted in mice, the research showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.

“In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor,” said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research (IBMR).

“In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.”

The research appears in the Aug. 21, 2013, issue of The Journal of Neuroscience.

Mice in this study were subjected to stress that might resemble a person’s response to persistent life stressors. In this model of stress, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.

Mice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms; mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals’ brains from the blood.

Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow. In previous studies, this same research group showed that cells in the brain called microglia, the brain’s first line of immune defense, are activated by prolonged stress and are partly responsible for the signals that call up monocytes from the bone marrow.

“There are different moving parts from the central and peripheral components, and what’s novel is them coming together to influence behavior,” said Jonathan Godbout, a senior co-author of the paper and an associate professor of neuroscience at Ohio State.

Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don’t respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state. These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.

“The monocytes are coming out of the bone marrow and they are not responsive to steroid regulation, so they overproduce proinflammatory signals when they’re stimulated. We think this is the key to the prolonged anxiety-like disorders that we see in these animals,” Sheridan said.

These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.

“Our data alter the idea of the neurobiology of mood disorders,” said Eric Wohleb, first author of the study and a predoctoral fellow in Ohio State’s Neuroscience Graduate Studies Program. “These findings indicate that a bidirectional system rather than traditional neurotransmitter pathways may regulate some forms of anxiety responses. We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”

(Source: newswise.com)

Filed under stress anxiety immune system animal model neuroscience science

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Schizophrenia symptoms linked to faulty ‘switch’ in brain Scientists at The University of Nottingham have shown that psychotic symptoms experienced by people with schizophrenia could be caused by a faulty ‘switch’ within the brain. In a study published today in the leading journal Neuron, they have demonstrated that the severity of symptoms such as delusions and hallucinations which are typical in patients with the psychiatric disorder is caused by a disconnection between two important regions in the brain — the insula and the lateral frontal cortex. The breakthrough, say the academics, could form the basis for better, more targeted treatments for schizophrenia with fewer side effects. The four-year study, led by Professor Peter Liddle and Dr Lena Palaniyappan in the University’s Division of Psychiatry and based in the Institute of Mental Health, centred on the insula region, a segregated ‘island’ buried deep within the brain, which is responsible for seamless switching between inner and outer world. "Powerful explanation" Dr Lena Palaniyappan, a Wellcome Trust Research Fellow, said: “In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex. This switch process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition. This could also explain the difficulties in ‘internalising’ external material pleasures (e.g. enjoying a musical tune or social events) that result in emotional blunting in patients with psychosis. Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms.” Several brain regions are engaged when we are lost in thought or, for example, remembering a past event. However, when interrupted by a loud noise or another person speaking we are able to switch to using our frontal cortex area of the brain, which processes this external information. With a disruption in the connections from the insula, such switching may not be possible. Compromised brain function The Nottingham scientists used functional MRI (fMRI) imaging to compare the brains of 35 healthy volunteers with those of 38 schizophrenic patients. The results showed that whereas the majority of healthy patients were able to make this switch between regions, the patients with schizophrenia were less likely to shift to using their frontal cortex. The insular and frontal cortex form a sensitive ‘salience’ loop within the brain — the insular should stimulate the frontal cortex while in turn the frontal cortex should inhibit the insula — but in patients with schizophrenia this system was found to be seriously compromised. The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could have a high degree of predictive value in identifying patients with schizophrenia. The results of the study offer vital information for the development of more effective treatments for the condition. Schizophrenia is one of the most common serious mental health conditions affecting around 1 in 100 people. Its onset occurs most commonly in a patient’s late teens or early 20s which can have devastating consequences for their future. Genetic and environmental triggers Scientists remain unsure what causes schizophrenia but believe it could be a combination of a genetic predisposition to the condition combined with environmental factors. Drug use is known to be a key trigger – people who use cannabis, or stimulant drugs, are three to four times more likely to go on to develop recurrent psychotic symptoms. It is also believed that underdevelopment of the brain in the womb caused by complications in the mother’s pregnancy and in early childhood linked to issues such as malnutrition could play a key part. Previous observations from this research group have also uncovered the presence of unusually smooth folding patterns of the brain over the insula region in patients, suggesting an impairment in the normal development of this structure in schizophrenia. At present, treatment involves a combination of antipsychotic medications, psychological therapies and social interventions. Currently, only one in five patients with schizophrenia achieve complete recovery and many patients who develop the condition in the long-term struggle to find a treatment that is 100 per cent effective in managing their condition. Antipsychotic drugs, though effective in a number of patients, have poor acceptance rates due to the side effect burden meaning that many patients stop taking them in the longer run, leading to recurrence of disabling symptoms. Researchers in Nottingham are also looking at a technique called TMS – transcranial magnetic stimulation — which uses a powerful magnetic pulse to stimulate the brain regions that are malfunctioning. Compassion-based therapy Despite the fact that the insular region is buried so deeply within the brain that TMS would usually be ineffective, the results of the Nottingham study suggest that the loop between the insular and the frontal cortex could be exploited for TMS– if a pulse is delivered to the frontal lobe it could stimulate the insula and reset the ‘switch’. Other future treatment options could include the use of a compassion-based meditation therapy called mindfulness, which may have the potential to ‘reset’ the switching function of the insula and can promote physical changes within the brain. Meditation over a long period of time has been shown to increase the folding patterns within the insula area of the brain. These ideas are in its early stages at present, but may deliver more focussed treatment approaches in the longer term.

Schizophrenia symptoms linked to faulty ‘switch’ in brain

Scientists at The University of Nottingham have shown that psychotic symptoms experienced by people with schizophrenia could be caused by a faulty ‘switch’ within the brain.

In a study published today in the leading journal Neuron, they have demonstrated that the severity of symptoms such as delusions and hallucinations which are typical in patients with the psychiatric disorder is caused by a disconnection between two important regions in the brain — the insula and the lateral frontal cortex.

The breakthrough, say the academics, could form the basis for better, more targeted treatments for schizophrenia with fewer side effects.

The four-year study, led by Professor Peter Liddle and Dr Lena Palaniyappan in the University’s Division of Psychiatry and based in the Institute of Mental Health, centred on the insula region, a segregated ‘island’ buried deep within the brain, which is responsible for seamless switching between inner and outer world.

"Powerful explanation"

Dr Lena Palaniyappan, a Wellcome Trust Research Fellow, said: “In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex. This switch process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition. This could also explain the difficulties in ‘internalising’ external material pleasures (e.g. enjoying a musical tune or social events) that result in emotional blunting in patients with psychosis. Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms.”

Several brain regions are engaged when we are lost in thought or, for example, remembering a past event. However, when interrupted by a loud noise or another person speaking we are able to switch to using our frontal cortex area of the brain, which processes this external information. With a disruption in the connections from the insula, such switching may not be possible.

Compromised brain function

The Nottingham scientists used functional MRI (fMRI) imaging to compare the brains of 35 healthy volunteers with those of 38 schizophrenic patients. The results showed that whereas the majority of healthy patients were able to make this switch between regions, the patients with schizophrenia were less likely to shift to using their frontal cortex.

The insular and frontal cortex form a sensitive ‘salience’ loop within the brain — the insular should stimulate the frontal cortex while in turn the frontal cortex should inhibit the insula — but in patients with schizophrenia this system was found to be seriously compromised.

The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could have a high degree of predictive value in identifying patients with schizophrenia.

The results of the study offer vital information for the development of more effective treatments for the condition.

Schizophrenia is one of the most common serious mental health conditions affecting around 1 in 100 people. Its onset occurs most commonly in a patient’s late teens or early 20s which can have devastating consequences for their future.

Genetic and environmental triggers

Scientists remain unsure what causes schizophrenia but believe it could be a combination of a genetic predisposition to the condition combined with environmental factors. Drug use is known to be a key trigger – people who use cannabis, or stimulant drugs, are three to four times more likely to go on to develop recurrent psychotic symptoms.

It is also believed that underdevelopment of the brain in the womb caused by complications in the mother’s pregnancy and in early childhood linked to issues such as malnutrition could play a key part. Previous observations from this research group have also uncovered the presence of unusually smooth folding patterns of the brain over the insula region in patients, suggesting an impairment in the normal development of this structure in schizophrenia.

At present, treatment involves a combination of antipsychotic medications, psychological therapies and social interventions. Currently, only one in five patients with schizophrenia achieve complete recovery and many patients who develop the condition in the long-term struggle to find a treatment that is 100 per cent effective in managing their condition.

Antipsychotic drugs, though effective in a number of patients, have poor acceptance rates due to the side effect burden meaning that many patients stop taking them in the longer run, leading to recurrence of disabling symptoms.

Researchers in Nottingham are also looking at a technique called TMS – transcranial magnetic stimulation — which uses a powerful magnetic pulse to stimulate the brain regions that are malfunctioning.

Compassion-based therapy

Despite the fact that the insular region is buried so deeply within the brain that TMS would usually be ineffective, the results of the Nottingham study suggest that the loop between the insular and the frontal cortex could be exploited for TMS– if a pulse is delivered to the frontal lobe it could stimulate the insula and reset the ‘switch’.

Other future treatment options could include the use of a compassion-based meditation therapy called mindfulness, which may have the potential to ‘reset’ the switching function of the insula and can promote physical changes within the brain. Meditation over a long period of time has been shown to increase the folding patterns within the insula area of the brain. These ideas are in its early stages at present, but may deliver more focussed treatment approaches in the longer term.

Filed under insula frontal cortex schizophrenia neuroimaging neuroscience psychology science

222 notes

Playing video games can boost brain power

Certain types of video games can help to train the brain to become more agile and improve strategic thinking, according to scientists from Queen Mary University of London and University College London (UCL).

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The researchers recruited 72 volunteers and measured their ‘cognitive flexibility’ described as a person’s ability to adapt and switch between tasks, and think about multiple ideas at a given time to solve problems.

Two groups of volunteers were trained to play different versions of a real-time strategy game called StarCraft, a fast-paced game where players have to construct and organise armies to battle an enemy. A third of the group played a life simulation video game called The Sims, which does not require much memory or many tactics.

All the volunteers played the video games for 40 hours over six to eight weeks, and were subjected to a variety of psychological tests before and after. All the participants happened to be female as the study was unable to recruit a sufficient number of male volunteers who played video games for less than two hours a week.

The researchers discovered that those who played StarCraft were quicker and more accurate in performing cognitive flexibility tasks, than those who played The Sims.

Dr Brian Glass from Queen Mary’s School of Biological and Chemical Sciences, said: “Previous research has demonstrated that action video games, such as Halo, can speed up decision making but the current work finds that real-time strategy games can promote our ability to think on the fly and learn from past mistakes.

“Our paper shows that cognitive flexibility, a cornerstone of human intelligence, is not a static trait but can be trained and improved using fun learning tools like gaming.”

Professor Brad Love from UCL, said:  “Cognitive flexibility varies across people and at different ages. For example, a fictional character like Sherlock Holmes has the ability to simultaneously engage in multiple aspects of thought and mentally shift in response to changing goals and environmental conditions.

“Creative problem solving and ‘thinking outside the box’ require cognitive flexibility. Perhaps in contrast to the repetitive nature of work in past centuries, the modern knowledge economy places a premium on cognitive flexibility.”

Dr Glass added: “The volunteers who played the most complex version of the video game performed the best in the post-game psychological tests. We need to understand now what exactly about these games is leading to these changes, and whether these cognitive boosts are permanent or if they dwindle over time. Once we have that understanding, it could become possible to develop clinical interventions for symptoms related to attention deficit hyperactivity disorder or traumatic brain injuries, for example.”

(Source: qmul.ac.uk)

Filed under video games cognition technology neuroscience science

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