Posts tagged neuroscience

April 1, 2012

Rutgers scientists think they have found a way to prevent and possibly reverse the most debilitating symptoms of a rare, progressive childhood degenerative disease that leaves children with slurred speech, unable to walk, and in a wheelchair before they reach adolescence.

In today’s online edition of Nature Medicine, Karl Herrup, chair of the Department of Cell Biology and Neuroscience in the School of Arts and Sciences provides new information on why this genetic disease attacks the cerebellum – a part of the brain that controls movement coordination, equilibrium, and muscle tone – and other regions of the brain.

Using mouse and human brain tissue studies, Herrup and his colleagues at Rutgers found that in the brain tissue of young adults who died from ataxia-telangiectasia, or A-T disease, a protein known as HDAC4 was in the wrong place. HDAC4 is known to regulate bone and muscle development, but it is also found in the nerve cells of the brain. The protein that is defective in A-T, they discovered, plays a critical role in keeping HDAC4 from ending up in the nucleus of the nerve cell instead of in the cytoplasm where it belongs. In a properly working nerve cell, the HDAC4 in the cytoplasm helps to prevent nerve cell degeneration; however, in the brain tissue of young adults who had died from A-T disease, the protein was in the nucleus where it attacked the histones – the small proteins that coat and protect the DNA.

"What we have found is a double-edged sword," said Herrup. "While the HDAC4 protein protected a neuron’s function when it was in the cytoplasm, it was lethal in the nucleus."

To prove this point, Rutgers scientists analyzed mice, genetically engineered with the defective protein found in children with A-T, as well as wild mice. The animals were tested on a rotating rod to measure their motor coordination. While the normal mice were able to stay on the rod without any problems for five to six minutes, the mutant mice fell off within 15 to 20 seconds.

After being treated with trichostation A (TSA), a chemical compound that inhibits the ability of HDAC4 to modify proteins, they found that the mutant mice were able to stay on the rotating rod without falling off – almost as long as the normal mice.

Although the behavioral symptoms and brain cell loss in the engineered mice are not as severe as in humans, all of the biochemical signs of cell stress were reversed and the motor skills improved dramatically in the mice treated with TSA. This outcome proves that brain cell function could be restored, Herrup said.

"The caveat here is that we have fixed a mouse brain with less devastation and fewer problems than seen in a child with A-T disease," said Herrup. "But what this mouse data says is that we can take existing cells that are on their way to death and restore their function."

Neurological degeneration is not the only life-threatening effect associated with this genetic disease. A-T disease – which occurs in an estimated 1 in 40,000 births – causes the immune system to break down and leaves children extremely susceptible to cancers such as leukemia or lymphoma. There is no known cure and most die in their teens or early 20s. According to the AT Children’s Project, many of those who die at a young age might not have been properly diagnosed, which may, in fact, make the disease even more common.

Herrup says although this discovery does not address all of the related medical conditions associated with the disease, saving existing brain cells – even those that are close to death – and restoring life-altering neurological functions would make a tremendous improvement in the lives of these children.

"We can never replace cells that are lost," said Herrup. "But what these mouse studies indicate is that we can take the cells that remain in the brains of these children and make them work better. This could improve the quality of life for these kids by unimaginable amounts."

Additionally, Herrup says, the research might provide insight into other neurodegenerative diseases. “If this is found to be true, then the work we’ve done on this rare disease of childhood may have a much wider application in helping to treat other diseases of the nervous system, even those that affect the elderly, like Alzheimer’s,” he said.

Provided by Rutgers University 

Source: medicalxpress.com

March 30th, 2012

A new animal model of nerve injury has brought to light a critical role of an enzyme called Nmnat in nerve fiber maintenance and neuroprotection. Understanding biological pathways involved in maintaining healthy nerves and clearing away damaged ones may offer scientists targets for drugs to mitigate neurodegenerative diseases such as Huntington’s and Parkinson’s, as well as aid in situations of acute nerve damage, such as spinal cord injury.

University of Pennsylvanian biologists developed the model in the adult fruit fly, Drosophila melanogaster.

“We are using the basic power of the fly to learn about how neurons are damaged in acute injury situations,” said Nancy Bonini, senior author of the research and a professor in the Department of Biology at Penn. “Our work indicates that Nmnat may be key.”

The research was published in Current Biology. First author on the study is postdoctoral researcher Yanshan Fang, with additional contributions from postdoctoral researcher Lorena Soares and research technicians Xiuyin Teng and Melissa Geary, all of Penn’s Department of Biology.

When a nerve suffers an acute injury — as might be caused by a penetrating wound, for example, or a broken bone that damages nearby tissues — the long projection of the nerve cell, called the axon, can become injured and degenerate. The process by which it disintegrates is known as Wallerian or Wallerian-like degeneration and is an active, orderly process.

Though this function of eliminating damaged nerve cells is crucial, biologists do not have a clear understanding of all of the molecular signaling pathways that govern the process.

Bonini’s lab has previously focused on chronic neurodegenerative diseases but made this foray into acute nerve injury to determine if mechanistic overlaps exist between acute axon injury and chronic neurodegeneration. They first searched for an appropriate nerve tract to target and identified the wing of adult flies as a prime option.

The fly wing is not only translucent and a site of lengthy nerve fibers that can be easily observed, but it can also be cut to cause injury without killing the fly. That way, the researchers can follow the animal’s response to nerve injury for weeks.

Using various reagents to manipulate the fly’s genetic traits, the team confirmed that the cut wing nerve underwent Wallerian degeneration. They then tested versions of Nmnat and another protein called Wld^S, all of which had previously been shown to protect nerves from degeneration, to see if any of these might stop the process. All significantly delayed neurodegeneration. Even a form of Nmnat that hadn’t worked in other animal models suppressed degeneration, although to a lesser extent.

“That indicates that our assay is really sensitive,” Bonini said. “This sensitivity could help us identify genes that have moderate although important functionality at protecting against nerve degeneration.”

Their investigations into the wing nerve also showed that the degenerating axon “died back,” fragmenting first from the axon terminals, the side farthest from the nerve cell body—a pattern similar to what has been seen in other disorders.

Doing more genetic tinkering, the researchers showed that when the animal’s own Nmnat was depleted, the nerves fragmented in the same way as if the axon was physically cut. And when Nmnat and the other “rescue” proteins were added back to these genetically modified flies, they were able to block degeneration, highlighting that Nmnat is critical to maintaining healthy axons.

In a final set of experiments, the biologists sought to narrow where in the nerve cells Nmnat might be working. They focused on mitochondria, the powerhouses of cells. When they created a genetic line of flies that blocked mitochondria from entering the axon fibers, the nerve tract degenerated, again, in a dying-back fashion. Yet now Wld^S and Nmnat failed to prevent axon degeneration, suggesting that those proteins may act on and require the presence of axonal mitochondria to maintain healthy nerves in normal flies.

Flipping that scenario around, they looked to see what happened to the mitochondria of flies upon nerve injury. When they cut the wing nerve axons, the mitochondria rapidly disappeared. Yet they can largely preserve the mitochrondria by increasing expression of Nmnat.

Their results, taken together with the findings of other studies, suggest that Nmnat may stabilize mitochondria in some way in order to keep axons in a healthy state.

“We have some hope that these proteins or their activity may someday serve as drug targets or could provide the foundation for a therapeutic advance,” Bonini said. “But right now, my hope is that the power of the fly model will open up a lot of new directions of research and new pathways that could be targets for development in the future.”

Source: Neuroscience News

16:55 30 March 2012

Sumit Paul-Choudhury, editor

My Soul, 2005, Katharine Dowson (Image: Image courtesy of the artist and GV Art)

LOOKING at your own brain is a humbling and slightly unnerving experience. Mine, depicted in a freshly acquired MRI scan, is startlingly intricate, compact - and baffling. This is as much of a portrait of my own mind as I am ever likely to see. But to my ignorant eyes (which, by way of an eerie bonus, are now looking at their own cross-sections) it looks pretty much like any other brain.

Apparently a more expert eye wouldn’t help. “Whilst all my participants get very excited about seeing their brain for the first time after being scanned, and I frequently get asked ‘What can you tell me about my brain?’, the reality is that the brain will for a long time yet remain a mysterious mass,” says the neuroscientist who scanned my brain, for research purposes. “We must be content with knowing that the ‘I’ is constructed in its intricacies, but we cannot explain how.”

The hope of closing the gap between the physical and mental is presumably what gets neuroscientists up in the morning, but it’s frustrating for a layperson like me. Avowed materialist though I am, I nonetheless rebel against the knowledge that the impassive blob on screen is “me”.

This cognitive dissonance was what I took with me to the opening of Brains, a new show at London’s Wellcome Collection, whose subtitle, “The Mind as Matter”, suggests that its curators sympathise with my materialist perspective. “The neurosciences hold out the prospect of an objective account of consciousness - the soul or mind as nothing more than intricately connected flesh,” reads the introduction. But the bulk of the exhibition is dedicated to whole brains, brain collectors and anatomical paraphernalia, with little explicit reference to the brain’s fine structure, or how it might give rise to thought.

This remit is less restrictive than it might sound. Evolution has seen to it that the most vital of our bodily organs is well guarded against intrusion, and as a by-product, well hidden from inspection. Even today, only a small minority of the population have seen their own brains - and many (unlike me, thankfully) have done so only when they had reason to be fearful of what they found.

So the history of attempts to access, visualise and understand the brain is a rich one. But it’s also well worn, and some of the historical material - elaborate anatomical models, kooky phrenological busts and grim-looking surgical implements - is over-familiar. The scientific objects are more compelling, albeit they also tend to the grotesque - from the arachnid contraptions used to measure skull size to the spools of finely-sliced mouse-brains on tape.

Much of the fascination lies not in the objects themselves, but in the human stories behind them, told in captions whose straight-facedness sometimes comes across as drollery or clinical detachment. Trepanning tools fashioned from flint and animal teeth “would have taken longer to cut through the skull than more modern instruments”, one informs us drily; the American Anthropometric Society was “basically a club to enable the leading men of US science to dissect each other,” says another.

Secluded in the skull, individual brains develop relatively few distinguishing features save those given them by trauma, disease or rare accidents of birth. So brains of note tend to be associated with tales of misfortune. That’s often the case with anatomical specimens, but what’s remarkable about the brains on display here is how much they overlap with criminality. Some of the most striking have been acquired from people whose wickedness in life was deemed sufficient reason to deny them dignity in death. In other cases, the moral equation is reversed, with collectors stepping outside the bounds of decency in their desire to possess the brain; the abhorrent nadir being reached with the probable murder of “feeble” children by Nazi doctors.

(Image: Science Museum, London)

The collection’s examples of brains being voluntarily donated are equally remarkable. Persuading someone to donate this most personal of organs is a tough sell, and the historical portion of the exhibition makes much of how appeals to ego have persuaded the great and good to offer up their brains for post-mortem examination. More recently, medical study has provided motivation for would-be donors. Particularly poignant is the tale of Anita Newcomb McGee, a female US army surgeon who gave up her nine-month old son’s brain, along with a photograph and a sketch of his head, with the words “I want him to benefit the world in some way if possible.”

But this altruism is tempered by the fact that brains, unlike many of our other “charismatic organs”, cannot conceivably be transplanted. The knowledge that someone else might gain life from my gifted heart is a powerful incentive to donate, but I have less incentive to be generous with my brain - though it would seem that distinction is not made by those who do donate. Perhaps reluctant donors might be won over by the moving photos compiled by artist Ania Dabrowska and social scientist Bronwyn Parry of cheerful would-be donors ranging from an ex-soldier to a headmistress.

And one of the exhibition’s stand-out exhibits might provide further reassurance: a documentary video of anatomists at London’s Hammersmith Hospital painstakingly and precisely slicing donated brains into half-centimetre wedges in near-silence. Or perhaps not. This is well sanctioned, respectful science being conducted on freely donated organs for the betterment of human health and knowledge; and yet it nonetheless provokes one of my fellow spectators into muttering, very much to herself: “Wrong, wrong, wrong”. For myself, I find the video one of the most compelling exhibits — perhaps the only one that prompts me to contemplate offering myself up for more than a non-invasive scan in the service of medical science.

Less clear-cut, for me, are the nearby sections of Einstein’s brain, preserved under deeply dubious circumstances after his death. Clearly, there’s a certain fascination associated with perhaps the most famous brain there ever was; but Einstein’s brain is no more legible than any other, and the slim prospect that scientific insights can be gleaned from its study seems poor recompense for the undignified proxying of a great mind by illicitly-obtained fragments of tissue.

(Image: Wellcome Library, London. Wellcome Images)

The final insult: an accompanying 3D-printed replica of the entire organ, reconstructed for a TV documentary from archive photographs. This absurd resin relic epitomises, for me, the extent to which the objects on display at the Wellcome are imbued with significance by the knowledge that they were once the seats of consciousness. It’s the minds of the audience, rather than the brains on display, that are doing the work.

The Wellcome show confronts its visitors with the gulf between our hard-won knowledge about the form of the brain and our as-yet-meagre understanding of its function, much as my scan did to me. It didn’t narrow the gap between the grey image of my brain and my sense of self; if anything, it widened it. But it did make me appreciate what an amazing gap it is, and marvel anew at the work of those who are seeking to close it.

Brains: The mind as matter is showing at the Wellcome Collection in London until 17 June.

Source: New Scientist

March 30, 2012

A team of neuroscientists from the Institute of Psychiatry (IoP) at King’s College London have developed a digital atlas of the human brain for iPad. The ‘Brain’ App is the first of its kind, and is based on cutting edge neuro-imaging research from the NatBrainLab at the IoP. 

Image taken from the ‘Brain’ Study Room

Dr. Marco Catani, Head of the NatBrainLab who led the development of the App with Dr. Flavio Dell’Acqua and Dr. Michel Thiebaut de Schotten, said: “For 10 years our lab has pioneered the use of highly advanced neuro-imaging techniques. This is the first time that imaging methods usually only applied to research have been used in an educational App. It’s very exciting to see our work transformed into such an accessible, fun and beautiful tool.”

Image taken from the ‘Brain’ Dissection Room

Two types of scans were used to develop the content of ‘Brain’ – results from an MRI scan reveal the structural properties of the brain, and images from a Diffusion Tractography scan allow the user to identify connections in the brain. 

The App is split into two virtual rooms. The Dissection Room allows the user to play with a 3D human brain, select individual structures and ‘pull’ them apart to visualize their anatomical features. The Study Room then offers a more thorough explanation of functional aspects and their relationship to neurological and psychiatric disorders. 

Dr. Catani adds: “The interactive nature of our App really allows you to explore the depths of the neural network and appreciate the complexity of the human brain. Because the content is based directly on research, the finished product is an accurate reflection of the real thing.”

Dr. Catani and his team are now working towards developing the next version of the App. By integrating scans from several different brains into the programme, they hope to be able to offer the user the chance to see directly how the brain develops from childhood to old age and the direct effect of different age-related disorders on the brain.

The App is currently being used by Dr. Catani and his colleagues to teach MSc students neuroscience.

Provided by King’s College London

Source: medicalxpress.com

March 30, 2012

(HealthDay) — Electrocorticography (ECoG) signals from patients with chronic motor dysfunction represent motor information that may be useful for controlling prosthetic arms, according to a study published in the March issue of the Annals of Neurology.

To investigate whether ECoG signals recorded from chronically paralyzed patients and whether those signals can be applied to control a prosthetic, Takufumi Yanagisawa, M.D., Ph.D., of the Osaka University Medical School in Japan, and colleagues recorded ECoG signals from sensorimotor cortices of 12 patients while they attempted to carry out three to five simple hand and elbow movements. Sensorimotor function was normal in five patients, moderately impaired due to central nervous system lesions sparing the cortex in four patients, and severely impaired due to peripheral nervous system lesion or amputation in three patients.

The researchers found that the high gamma power (80 to 150 Hz) of the ECoG signals during movements was responsive to different types of movement and provided the best information for movement classification. In all patients, the classification performance was significantly better than chance, although for patients with severely impaired motor function the differences between ECoG power modulations during different types of movement were significantly fewer. Cortical representations tended to overlap each other in impaired patients. One moderately impaired patient and three non-paralyzed patients successfully controlled a prosthetic arm using the classification method in real time.

"ECoG signals appear useful for prosthetic arm control and may provide clinically feasible motor restoration for patients with paralysis but no injury of the sensorimotor cortex," the authors write.

Abstract

Source: medicalxpress.com

March 30, 2012

An estimated 2.2 million people in the United States live with epilepsy, a complex brain disorder characterized by sudden and often unpredictable seizures. The highest rate of onset occurs in children and older adults, and it affects people of all ethnicities and socio-economic backgrounds, yet this common disorder is widely misunderstood. Epilepsy refers to a spectrum of disorders with seizures that vary in type, cause, severity, and frequency. Many people do not know the causes of epilepsy or what measures to take if they witness a seizure. A new report from the Institute of Medicine highlights numerous gaps in the knowledge and management of epilepsy and recommends actions for improving the lives of those with epilepsy and their families and promoting better understanding of the disorder.

Effective treatments for epilepsy are available but access to treatment and timely referrals to specialized care are often lacking, the report’s expert committee found. Reaching rural and underserved populations, as well as providing state-of-the art care for people with persistent seizures, is particularly crucial. The report’s recommendations for expanding access to patient-centered health care include early identification and treatment of epilepsy and associated health conditions, implementing measures that assess quality of care, and establishing accreditation criteria and processes for specialized epilepsy centers. In addition, the wide variety of health professionals who care for those with epilepsy need improved knowledge and skills to provide the highest quality health care.

Some causes of epilepsy, such as traumatic brain injury, infection, and stroke, are preventable. Prevention efforts should continue for these established risk factors, as well as for recurring seizures in people with epilepsy and depression, and for epilepsy-related causes of death, the report says.

People with epilepsy need additional education and skills to optimally manage their disorder. Consistent delivery of accurate, clearly communicated health information from sources that include health care professionals and epilepsy organizations can better prepare those with epilepsy and their families to cope with the disorder and its consequences, the report says. Accurate, current data on the extent and consequences of epilepsy and its associated health conditions are especially needed to inform policymakers and identify opportunities for reducing the burden of epilepsy.

Living with epilepsy can affect employment, driving ability, and many other aspects of quality of life. The report stresses the importance of improved access to a range of community services, including vocational, educational, transportation, transitional care, and independent living assistance as well as support groups. The committee urged collaboration among federal agencies, state health departments, and relevant epilepsy organizations to improve and integrate these services and programs, particularly at state and local levels.

Misperceptions about epilepsy persist and a focus on raising public awareness and knowledge is needed, the report adds. Educating community members such as teachers, employers, and others on how to manage seizures could help improve public understanding of epilepsy. The report suggests several strategies for stakeholders to improve public knowledge of the disorder, including forming partnerships with the media, establishing advisory councils, and engaging people with epilepsy and their families to serve as advocates and educators within their communities.

Provided by National Academy of Sciences

Source: medicalxpress.com

March 30, 2012

Researchers want to help the Army better camouflage its soldiers and break the enemy’s efforts to hide.

Researchers Jay Hegde and Xing Chen are using functional MRI to look at the brains of study participants learning how to break camouflage in order to help identify soldiers who will be good at it and identify better ways to teach it. Credit: Phil Jones, GHSU Photographer

"We want to make our camouflage unbreakable and we want to break the camouflage of the enemy," said Dr. Jay Hegde, neuroscientist in the Medical College of Georgia at Georgia Health Sciences University.

Hegde and GHSU Postdoctoral Fellow Dr. Xing Chen are using a relatively simple technique they developed to teach civilian volunteers to break camouflage. They flash a series of camouflage pictures on a computer screen, providing about a half second after each to spot, for instance, a face in a sea of mushrooms. A green light signals a correct answer and a red light signals an incorrect answer. The computer-generated images include distractions to make the difficult task even more challenging.

They are finding that an hour of daily training in as little as two weeks results in proficiency for 60 percent of the mostly college and graduate school students who have signed up for their training. The Army’s current approach is taking soldiers into battlefield situations to hone these skills.

As part of a three-year grant from the Office of Army Research, the researchers want to determine which parts of the brain light up when trained snipers break camouflage.

"We need to figure out how the expert camouflage-breakers do it," Hegde said. "We want to figure out what parts of the brain are most responsive when people break camouflage and, a related experiment is what part of the brain changes its response when people learn to break camouflage." Their techniques include functional magnetic resonance imaging to measure blood flow activity as an indicator of brain cell activity.

Figuring out which parts of the brain are involved could give the Army and others a better way to identify future first-rate snipers and objectively assess instructional efforts.

"If you are the Dean of the Army Sniper Corps and want to develop top-notch snipers, you don’t want to spend a year training them before giving up on half of them," Hegde said. A brain scan could help signal whose relevant areas are well developed and, consequently, have natural skill. 

Early evidence points toward two regions of the temporal lobe, found on either side of the brain and known to have a role in speech and vision. A region called the fusiform gyrus – which plays a role in facial recognition and lights up when people become experts at recognizing various objects, such as a particular bird species – may be important in breaking camouflage as well.

Hegde suspects that expertise at breaking camouflage stems from the fusiform gyrus in combination with some other area(s) of the brain. And, because good recognition skills don’t typically translate from one area to another, he also suspects that the parts of the brain involved vary with the object of their attention. For example, the ability to easily recognize the make and model of a car doesn’t guarantee skill at breaking camouflage and Hegde notes that some military snipers aren’t good at game-hunting.

Vision happens when light enters the retina where photoreceptor cells turn it into signals that are interpreted by the brain. “If there is a whole lot of light falling on them, they send a lot of signals, beep, beep, beep,” he said in rapid succession. “If there is a little bit of light they fire slowly.” The brain connects the dots to form a familiar face or landscape. Camouflage complicates the task – the difference between recognizing a mountain goat against a clear blue sky and finding a moth among a pile of fall leaves.

"Here is the beautiful thing that we are finding out: if you know what you are looking for, the next time you can break the camouflage of the moth. Without knowing what you are looking for, the picture also is ambiguous," Hegde said.

Provided by Georgia Health Sciences University

Source: medicalxpress.com

ScienceDaily (Mar. 30, 2012) — Human attention to a particular portion of an image alters the way the brain processes visual cortex responses to that image.

A schematic diagram of the contrast discrimination task, showing the focal cue trial (top row) and the distributed cue trial (bottom row). The contrast within the top right circle increases from the first interval (second column) to the second interval (fourth column). The third column is the interstimulus interval. (Credit: Copyright 2011 Elsevier Inc.)

Our ability to ignore some, but not other stimuli, allows us to focus our attention and improve our performance on a specific task. The ability to respond to visual stimuli during a visual task hinges on altered brain processing of responses within the visual cortex at the back of the brain, where visual information is first received from the eyes. How this occurs was recently demonstrated by an international team of researchers led by Justin Gardner at the RIKEN Brain Science Institute in Wako.

In a contrast discrimination task, the researchers showed three observers a stimulus of a group of four circles, each containing grey and white bars that created stripes of different contrasts. After a short pause, the researchers showed the circles again, but the contrast within one of the circles was different. The observers were instructed to choose which group of circles contained the higher contrast.

In ‘focal cue trials’, an arrow directed the observers’ attention to a particular circle. In ‘distributed cue’ trials’, four arrows directed their attention diffusely, across all four circles. Gardner and colleagues found that the observers’ performance was better in the focal cue trials.

Using a magnetic resonance imaging (MRI) scanner, the research team was able to map the precise location within the visual cortex that was activated by the visual information within each of the four circles. During the contrast discrimination task, Gardner and colleagues could therefore measure the observers’ visual cortex activity elicited by the stimuli. In this way, they could correlate brain activity in the visual cortex with the observers’ attention and their choice of contrasting circles.

Visual cortex responses tended to be largest when the observers were paying attention to a particular target circle, and smallest when they were ignoring a circle. The researchers determined that the largest visual cortex responses to the stimuli guided the eventual choice of each observer, leading to enhanced performance on the visual task.

"We used computational modeling to test various hypotheses about how attention affects brain processing of visual information to improve behavioral performance," explains Gardner. "We concluded that the observers’ attention causes their brains to select the largest cortical response to guide contrast choice, since we found that an ‘efficient selection’ model best explained the behavioral and fMRI data," he says.

If the findings extend to other senses, such as hearing, researchers may begin to understand how humans make sense of a perceptually cluttered world.

Source: Science Daily

ScienceDaily (Mar. 29, 2012) — A type of cell plentiful in the brain, long considered mainly the stuff that holds the brain together and oft-overlooked by scientists more interested in flashier cells known as neurons, wields more power in the brain than has been realized, according to new research published March 29 in Science Signaling.

Human astrocytes. (Credit: Image courtesy of University of Rochester Medical Center)

Neuroscientists at the University of Rochester Medical Center report that astrocytes are crucial for creating the proper environment for our brains to work. The team found that the cells play a key role in reducing or stopping the electrical signals that are considered brain activity, playing an active role in determining when cells called neurons fire and when they don’t.

That is a big step forward from what scientists have long considered the role of astrocytes — to nurture neurons and keep them healthy.

"Astrocytes have long been called housekeeping cells — tending to neurons, nurturing them, and cleaning up after them," said Maiken Nedergaard, M.D., D.M.Sc., professor of Neurosurgery and leader of the study. "It turns out that they can influence the actions of neurons in ways that have not been realized."

Proper brain function relies on billions of electrical signals — tiny molecular explosions, really — happening remarkably in sync. Recalling the face of a loved one, swinging a baseball bat, walking down the street — all those actions rely on electrical signals passed instantly along our nerves like a molecular hot potato from one brain cell to another.

For that to happen, the molecular brew of chemicals like sodium, calcium and potassium that brain cells reside in must be just right — and astrocytes help to maintain that balanced environment. For instance, when a neuron sends an impulse, or fires, levels of potassium surrounding the cell jump dramatically, and those levels must come down immediately for the brain to work properly. Scientists have long known that that’s a job for astrocytes — sopping up excess potassium, ending the nerve pulse, and restoring the cells so they can fire again immediately.

In the paper in Science Signaling, Nedergaard’s team discovered an expanded role for astrocytes. The team learned that in addition to simply absorbing excess potassium, astrocytes themselves can cause potassium levels around the neuron to drop, putting neuronal signaling to a stop.

"Far from only playing a passive role, astrocytes can initiate the uptake of potassium in a way that affects neuronal activity," said Nedergaard. "It’s a simple, yet powerful mechanism for astrocytes to rapidly modulate neuronal activity."

Nedergaard has investigated the secret lives of astrocytes for more than two decades. She has shown how the cells communicate using calcium to signal. Nearly 20 years ago in a paper in Science, she pioneered the idea that glial cells like astrocytes communicate with neurons and affect them. Since then, has been a lot of speculation by other scientists that chemicals call gliotransmitters, such as glutamate and ATP, are key to this process.

In contrast, in the latest research Nedergaard’s team found that another signaling system involving potassium is at work. By sucking up potassium, astrocytes quell the firing of neurons, increasing what scientists call “synaptic fidelity.” Important brain signals are crisper and clearer because there is less unwanted activity or “chatter” among neurons that should not be firing. Such errant neuronal activity is linked to a plethora of disorders, including epilepsy, schizophrenia, and attention-deficit disorder.

"This gives us a new target for a disease like epilepsy, where signaling among brain cells is not as controlled as it should be," said Nedergaard, whose team is based in the Division of Glia Disease and Therapeutics of the Center for Translational Neuromedicine. of the Department of Neurosurgery

The first authors of the paper are Fushun Wang, Ph.D., research assistant professor of Neurosurgery; and graduate student Nathan Anthony Smith. They did much of the work by using a sophisticated laser-based system to monitor the activity of astrocytes in the living brain of rats and mice. The work by Smith, a graduate student in the University’s neuroscience program, was supported by a Kirschstein National Research Service Award from the National Institute of Neurological Disorders and Stroke (NINDS).

Other authors from Rochester include Takumi Fujita, Ph.D., post-doctoral associate; Takahiro Takano, Ph.D., assistant professor; Qiwu Xu, technical associate; and Lane Bekar, Ph.D., formerly research assistant professor, now at the University of Saskatchewan. Also contributing were Akemichi Baba of Hyogo University of Health Sciences in Japan, and Toshio Matsuda of Osaka University in Japan.

Nedergaard notes that the complexity and size of our astrocytes is one of few characteristics that differentiate our brains from rodents. Our astrocytes are bigger, faster, and much more complex in both structure and function. She has found that astrocytes contribute to conditions like stroke, Alzheimer’s, epilepsy, and spinal cord injury.

"Astrocytes are integral to the most sophisticated brain processes," she added.

Source: Science Daily

ScienceDaily (Mar. 29, 2012) — Certain genes and proteins that promote growth and development of embryos also play a surprising role in sending chemical signals that help adults learn, remember, forget and perhaps become addicted, University of Utah biologists have discovered.

This is a microscope image of the roundworm or nematode C. elegans with its nervous system glowing green due to labeling with a green jellyfish protein. (Credit: Penelope Brockie, University of Utah.)

"We found that these molecules and signaling pathways [named Wnt] do not retire after development of the organism, but have a new and surprising role in the adult. They are called back to action to change the properties of the nervous system in response to experience," says biology Professor Andres Villu Maricq, senior author of the new study in the March 30 issue of the journal Cell.

The study was performed in C. elegans — the millimeter-long roundworm or nematode — which has a nervous system that serves as a model for those of vertebrate animals, including humans.

Because other Wnt pathways in worms are known to work in humans too, the researchers believe that Wnt genes, the Wnt proteins they produce and so-called “Wnt signaling” also are involved in human learning, memory and forgetting.

"Almost certainly what we have discovered is going on in our brain as well," Maricq says. And because a worm nerve-signal "receptor" in the study is analogous to a human nicotine receptor involved in addiction, schizophrenia and some other mental disorders, some of the genes identified in the worm study "represent possible new targets for treatment of schizophrenia and perhaps addiction," he adds.

Wnt genes and their proteins already were known to “pattern the development and distribution of organs in the body” during embryo development, and to be responsible for various cancers and developmental defects when mutated, he says.

Maricq conducted the study with these Utah biologists: doctoral students Michael Jensen and Dane Maxfield; postdoctoral researchers Michael M. Francis, Frederic Hoerndli and Rui Wang; undergraduate Erica Johnson; Penelope Brockie, a research associate professor; and David M. Madsen, a senior research specialist.

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