Chapter 3. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals


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By Lenny Bernstein There are 60 million epileptics on the planet, and while advances in medication and implantable devices have helped them, the ability to better detect and even predict when they will have debilitating seizures would be a significant improvement in their everyday lives. Imagine, for example, if an epileptic knew with reasonable certainty that his next seizure would not occur for an hour or a day or a week. That might allow him to run to the market or go out for the evening or plan a short vacation with less concern. Computers and even dogs have been tested in the effort to do this, but now a group of organizations battling epilepsy is employing "big data" to help. They sponsored an online competition that drew 504 entrants who tried to develop algorithms that would detect and predict epileptic seizures. Instead of the traditional approach of asking researchers in a handful of labs to tackle the problem, the groups put huge amounts of data online that was recorded from the brains of dogs and people as they had seizures over a number of months. They then challenged anyone interested to use the information to develop detection and prediction models. "Seizure detection and seizure prediction," said Walter J. Koroshetz, deputy director of the National Institute of Neurological Disorders and Stroke (NINDS), are "two fundamental problems in the field that are poised to take significant advantage of large data computation algorithms and benefit from the concept of sharing data and generating reproducible results."

Keyword: Epilepsy
Link ID: 20403 - Posted: 12.08.2014

by Hal Hodson Yet another smartwatch launched this week. Called Embrace, it is rather different from the latest offerings from Apple, Samsung and Motorola: it can spot the warning signs of an epileptic seizure. Embrace was developed by Matteo Lai and his team at a firm called Empatica, with the help of Rosalind Picard at the Massachusetts Institute of Technology. It measures the skin's electrical activity as a proxy for changes deep in the brain, and uses a model built on years of clinical data to tell which changes portend a seizure. It also gathers the usual temperature and motion data that smartwatches collect, allowing the wearer to measure physical activity and sleep quality. Empatica launched a crowdfunding campaign on Indiegogo on Tuesday and has already raised more than $120,000. Backers who pledge $169 will receive an Embrace watch. The idea for the wristband came when Picard and her colleagues were running a study on the emotional states of children with autism, measuring skin conductance at the wrist as part of the study. Picard noticed that one of the children had registered a spike in electrical activity that turned out to have happened 20 minutes before they noticed the symptoms of a seizure. "It shocked me when I realised these things were showing up on the wrist," says Picard. The whole point of Embrace is to prevent sudden unexplained death in epilepsy (SUDEP). Its causes are not fully understood, but Picard says they understand enough to know how to reduce the chances of dying after an epileptic seizure. © Copyright Reed Business Information Ltd.

Keyword: Epilepsy; Robotics
Link ID: 20348 - Posted: 11.24.2014

By Esther Hsieh A little-known fact: the tongue is directly connected to the brain stem. This anatomical feature is now being harnessed by scientists to improve rehabilitation. A team at the University of Wisconsin–Madison recently found that electrically stimulating the tongue can help patients with multiple sclerosis (MS) improve their gait. MS is an incurable disease in which the insulation around the nerves becomes damaged, disrupting the communication between body and brain. One symptom is loss of muscle control. In a study published in the Journal of Neuro-Engineering and Rehabilitation, Wisconsin neuroscientist Yuri Danilov and his team applied painless electrical impulses to the tip of the tongue of MS patients during physical therapy. Over a 14-week trial, patients who got tongue stimulation improved twice as much on variables such as balance and fluidity as did a control group who did the same regimen without stimulation. The tongue has extensive motor and sensory integration with the brain, Danilov explains. The nerves on the tip of the tongue are directly connected to the brain stem, a crucial hub that directs basic bodily processes. Previous research showed that sending electrical pulses through the tongue activated the neural network for balance; such activation may shore up the circuitry weakened by MS. The team is also using tongue stimulation to treat patients with vision loss, stroke damage and Parkinson's. “We have probably discovered a new way for the neurorehabilitation of many neurological disorders,” Danilov says. © 2014 Scientific American

Keyword: Multiple Sclerosis
Link ID: 20332 - Posted: 11.20.2014

By DENISE GRADY An electrical device glued to the scalp can slow cancer growth and prolong survival in people with the deadliest type of brain tumor, researchers reported on Saturday. The device is not a cure and, on average, adds only a few months of life when used along with the standard regimen of surgery, radiation and chemotherapy. Some doctors have questioned its usefulness. But scientists conducting a new study said the device was the first therapy in a decade to extend life in people with glioblastomas, brain tumors in which median survival is 15 months even with the best treatment. The disease affects about 10,000 people a year in the United States and is what killed Senator Edward M. Kennedy in 2009. It is so aggressive and hard to treat that even seemingly small gains in survival are considered important. The new findings mean the device should become part of the standard care offered to all patients with newly diagnosed glioblastomas, the researchers conducting the study said. The equipment consists of four pads carrying transducer arrays that patients glue to their scalps and change every few days. Wires lead to a six-pound operating system and power supply. Except for some scalp irritation, the device has no side effects, the study found. But patients have to wear it more or less around the clock and must keep their heads shaved. It generates alternating, low-intensity electrical fields — so-called tumor-treating fields — that can halt tumor growth by stopping cells from dividing, which leads to their death. The researchers said the technology might also help treat other cancers, and would be tested in mesothelioma and cancers of the lung, ovary, breast and pancreas. © 2014 The New York Times Company

Keyword: Miscellaneous
Link ID: 20319 - Posted: 11.17.2014

By JAMES GORMAN Research on the brain is surging. The United States and the European Union have launched new programs to better understand the brain. Scientists are mapping parts of mouse, fly and human brains at different levels of magnification. Technology for recording brain activity has been improving at a revolutionary pace. The National Institutes of Health, which already spends $4.5 billion a year on brain research, consulted the top neuroscientists in the country to frame its role in an initiative announced by President Obama last year to concentrate on developing a fundamental understanding of the brain. Scientists have puzzled out profoundly important insights about how the brain works, like the way the mammalian brain navigates and remembers places, work that won the 2014 Nobel Prize in Physiology or Medicine for a British-American and two Norwegians. So many large and small questions remain unanswered. How is information encoded and transferred from cell to cell or from network to network of cells? Science found a genetic code but there is no brain-wide neural code; no electrical or chemical alphabet exists that can be recombined to say “red” or “fear” or “wink” or “run.” And no one knows whether information is encoded differently in various parts of the brain. Brain scientists may speculate on a grand scale, but they work on a small scale. Sebastian Seung at Princeton, author of “Connectome: How the Brain’s Wiring Makes Us Who We Are,” speaks in sweeping terms of how identity, personality, memory — all the things that define a human being — grow out of the way brain cells and regions are connected to each other. But in the lab, his most recent work involves the connections and structure of motion-detecting neurons in the retinas of mice. Larry Abbott, 64, a former theoretical physicist who is now co-director, with Kenneth Miller, of the Center for Theoretical Neuroscience at Columbia University, is one of the field’s most prominent theorists, and the person whose name invariably comes up when discussions turn to brain theory. © 2014 The New York Times Company

Keyword: Brain imaging
Link ID: 20302 - Posted: 11.11.2014

Mo Costandi The father of modern neuroscience had a sharp eye and an even sharper mind, but he evidently overlooked something rather significant about the basic structure of brain cells. Santiago Ramón y Cajal spent his entire career examining and comparing nervous tissue from different species. He observed the intricate branches we now call dendrites, and the thicker axonal fibres. He also recognised them as distinct components of the neuron, and convinced others that neurons are fundamental components of the nervous system. For Cajal, these cells were “the mysterious butterflies of the soul… whose beating of wings may one day reveal to us the secrets of the mind.” He hunted for them in “the gardens of the grey matter” and, being an accomplished artist, meticulously catalogued the many “delicate and elaborate forms” that they take. As his beautiful drawings show, all neurons have a single axon emanating from one area of the cell body, and one or more dendrites arising from another. This basic structure has been enshrined in textbooks ever since. But there appear to be unusual varieties of soul butterflies that Cajal failed to spot – neuroscientists in Germany have identified neurons that have axons growing from their dendrites, a discovery that challenges our century-old assumption about the form and function of these cells. Cajal stated that information flows through neurons in only one direction – from the dendrites, which receive electrical impulses from other neurons, to the cell body, which processes the information and conveys it to the initial segment of the axon, which then produces its own impulses that travel down it to the nerve terminal. (He indicated this with small arrows in some of his diagrams, such as the one above.) © 2014 Guardian News and Media Limited

Keyword: Brain imaging
Link ID: 20301 - Posted: 11.11.2014

By Amy Robinson Whether you’re walking, talking or contemplating the universe, a minimum of tens of billions of synapses are firing at any given second within your brain. “The weak link in understanding ourselves is really about understanding how our brains generate our minds and how our minds generate our selves,” says MIT neuroscientist Ed Boyden. One cubic millimeter in the brain contains over 100,000 neurons connected through a billion synapses computing on a millisecond timescale. To understand how information flows within these circuits, we first need a “brain parts” list of neurons and glia. But such a list is not enough. We’ll also need to chart how cells are connected and to monitor their activity over time both electrically and chemically. Researchers can do this at small scale thanks to a technology developed in the 1970s called patch clamping. Bringing a tiny glass needle very near to a neuron living within a brain allows researchers to perform microsurgery on single neurons, piercing the cell membrane to do things like record the millivolt electrical impulses flowing through it. Patch clamping also facilitates measurement of proteins contained within the cell, revealing characteristic molecules and contributing to our understanding of why one neuron may behave differently than another. Neuroscientists can even inject glowing dyes in order to see the shape of cells. Patch clamping is a technique that has been used in neuroscience for 40 years. Why now does it make an appearance as a novel neuroscience technology? In a word: robots. © 2014 Scientific American

Keyword: Brain imaging
Link ID: 20279 - Posted: 11.05.2014

by Clare Wilson Call them the neuron whisperers. Researchers are eavesdropping on conversations going on between brain cells in a dish. Rather than hearing the chatter, they watch neurons that have been genetically modified so that the electrical impulses moving along their branched tendrils cause sparkles of red light (see video). Filming these cells at up to 100,000 frames a second is allowing researchers to analyse their firing in unprecedented detail. Until recently, a neuron's electrical activity could only be measured with tiny electrodes. As well as being technically difficult, such "patch clamping" only reveals the voltage at those specific points. The new approach makes the neuron's entire surface fluoresce as the impulse passes by. "Now we see the whole thing sweep through," says Adam Cohen of Harvard University. "We get much more information - like how fast and where does it start and what happens at a branch." The idea is a reverse form of optogenetics – where neurons are given a gene from bacteria that make a light-sensitive protein, so the cells fire when illuminated. The new approach uses genes that make the neurons do the opposite - glow when they fire. "It's pretty cool," says Dimitri Kullmann of University College London. "It's amazing that you can dispense with electrodes." Cohen's team is using the technique to compare cells from typical brains with those from people with disorders such as motor neuron disease or amyotrophic lateral sclerosis. Rather than taking a brain sample, they remove some of the person's skin cells and grow them alongside chemicals that rewind the cells into an embryonic-like state. Another set of chemicals is used to turn these stem cells into neurons. "You can recreate something reminiscent of the person's brain in the dish," says Cohen. © Copyright Reed Business Information Ltd.

Keyword: Brain imaging
Link ID: 20241 - Posted: 10.25.2014

|By Bret Stetka Multiple sclerosis (MS) is an electrical disorder, or rather one of impaired myelin, a fatty, insulating substance that better allows electric current to bolt down our neurons and release the neurotransmitters that help run our bodies and brains. Researchers have speculated for some time that the myelin degradation seen in MS is due, at least in part, to autoimmune activity against the nervous system. Recent work presented at the MS Boston 2014 Meeting suggests that this aberrant immune response begins in the gut. Eighty percent of the human immune system resides in the gastrointestinal tract. Alongside it are the trillions of symbiotic bacteria, fungi and other single-celled organisms that make up our guts’ microbiomes. Normally everyone wins: The microorganisms benefit from a home and a steady food supply; we enjoy the essential assistance they provide in various metabolic and digestive functions. Our microbiomes also help calibrate our immune systems, so our bodies recognize which co-inhabitants should be there and which should not. Yet mounting evidence suggests that when our resident biota are out of balance, they contribute to numerous diseases, including diabetes, rheumatoid arthritis, autism and, it appears, MS by inciting rogue immune activity that can spread throughout the body and brain. One study presented at the conference, out of Brigham and Women’s Hospital (BWH), reported a single-celled organism called methanobrevibacteriaceae that activates the immune system is enriched in the gastrointestinal tracts of MS patients whereas bacteria that suppress immune activity are depleted. Other work, which resulted from a collaboration among 10 academic researcher centers across the U.S. and Canada, reported significantly altered gut flora in pediatric MS patients while a group of Japanese researchers found that yeast consumption reduced the chances of mice developing an MS-like disease by altering gut flora. © 2014 Scientific American

Keyword: Multiple Sclerosis
Link ID: 20186 - Posted: 10.09.2014

|By Nathan Collins Step aside, huge magnets and radioactive tracers—soon some brain activity will be revealed by simply training dozens of red lights on the scalp. A new study in Nature Photonics finds this optical technique can replicate functional MRI experiments, and it is more comfortable, more portable and less expensive. The method is an enhancement of diffuse optical tomography (DOT), in which a device shines tiny points of red light at a subject's scalp and analyzes the light that bounces back. The red light reflects off red hemoglobin in the blood but does not interact as much with tissues of other colors, which allows researchers to recover an fMRI-like image of changing blood flow in the brain at work. For years researchers attempting to use DOT have been limited by the difficulty of packing many heavy light sources and detectors into the small area around the head. They also needed better techniques for analyzing the flood of data that the detectors collected. Now researchers at Washington University in St. Louis and the University of Birmingham in England report they have solved those problems and made the first high-density DOT (HD-DOT) brain scans. The team first engineered a “double halo” structure to support the weight of 96 lights and 92 detectors, more than double the number in earlier arrays. The investigators also dealt with the computing challenges associated with that many lights—for example, they figured out how to filter out interference from blood flow in the scalp and other tissues. The team then used HD-DOT to successfully replicate fMRI studies of vision and language processing—a task impossible for other fMRI alternatives, such as functional near-infrared spectroscopy or electroencephalography, which do not cover a large enough swath of the brain or have sufficient resolution to pinpoint active brain areas. Finally, the team scanned the brains of people who have implanted electrodes for Parkinson's disease—something fMRI can never do because the machine generates electromagnetic waves that can destroy electronic devices such as pacemakers. © 2014 Scientific American

Keyword: Brain imaging
Link ID: 20151 - Posted: 10.02.2014

Michael Häusser Use light to read out and control neural activity! This idea, so easily expressed and understood, has fired the imagination of neuroscientists for decades. The advantages of using light as an effector are obvious1: it is noninvasive, can be precisely targeted with exquisite spatial and temporal precision, can be used simultaneously at multiple wavelengths and locations, and can report the presence or activity of specific molecules. However, despite early progress2 and encouragement3, it is only recently that widely usable approaches for optical readout and manipulation of specific neurons have become available. These new approaches rely on genetically encoded proteins that can be targeted to specific neuronal subtypes, giving birth to the term 'optogenetics' to signal the combination of genetic targeting and optical interrogation4. On the readout side, highly sensitive probes have been developed for imaging synaptic release, intracellular calcium (a proxy for neural activity) and membrane voltage. On the manipulation side, a palette of proteins for both activation and inactivation of neurons with millisecond precision using different wavelengths of light have been identified and optimized. The extraordinary versatility and power of these new optogenetic tools are spurring a revolution in neuroscience research, and they have rapidly become part of the standard toolkit of thousands of research labs around the world. Although optogenetics may not yet be a household word (though try it on your mother; she may surprise you), there can be no better proof that optogenetics has become part of the scientific mainstream than the 2013 Brain Prize being awarded to the sextet that pioneered optogenetic manipulation ( and the incorporation of optogenetics as a central plank in the US National Institutes of Health BRAIN Initiative5. Moreover, there is growing optimism about the prospect of using optogenetic probes not only to understand mechanisms of disease in animal models but also to treat disease in humans, particularly in more accessible parts of the brain such as the retina6. © 2014 Macmillan Publishers Limited

Keyword: Brain imaging
Link ID: 20142 - Posted: 10.01.2014

By Larry Greenemeier Former Grateful Dead percussionist Mickey Hart takes pride in his brain. Large, anatomically realistic 3-D animations representing the inner workings of his gray and white matter have graced video screens at several science and technology conferences. These “Glass Brain” visualizations use imaging and advanced computing systems to depict in colorful detail the fiber pathways that make Hart’s brain tick. The researchers behind the project hope it will also form the basis of a new type of tool for the diagnosis and treatment of neurological disorders. Each Glass Brain animation overlays electroencephalography (EEG) data collected in real time atop a magnetic resonance imaging (MRI) scan—in this case Hart’s—to illustrate how different brain areas communicate with each other. Special algorithms coded into software digitally reconstruct this activity within the brain. The result is a tour of the brain that captures both the timing and location of brain signals. Hart demonstrated the Glass Brain at a computer conference in San Jose, Calif., this past March by playing a video game called NeuroDrummer on stage. The drummer is working with the Studio Bee digital animation house in San Francisco as well as the Glass Brain’s creators to develop NeuroDrummer into a tool that can determine whether teaching someone to keep a drumbeat might help improve the neural signals responsible for cognition, memory and other functions. The Glass Brain’s brain trust includes the University of California, San Francisco’s Neuroscape Lab as well as the University of California, San Diego’s Swartz Center for Computational Neuroscience, EEG maker Cognionics, Inc. and NVIDIA, a maker of extremely fast graphics processing unit (GPU) computer chips and host of the conference where Hart performed. © 2014 Scientific American,

Keyword: Brain imaging
Link ID: 20137 - Posted: 09.30.2014

2014 by Helen Thomson Shall I compare thee to... well, no one actually. A 76-year-old woman has developed an incredibly rare disorder – she has the compulsive urge to write poetry. Her brain is now being studied by scientists who want to understand more about the neurological basis for creativity. In 2013, the woman arrived at a UK hospital complaining of memory problems and a tendency to lose her way in familiar locations. For the previous two years, she had experienced occasional seizures. She was diagnosed with temporal lobe epilepsy and treated with the drug lamotrigine, which stopped her seizures. However, as they receded, a strange behaviour took hold. She began to compulsively write poetry – something she hadn't shown any interest in previously. Suddenly, the woman was writing 10 to 15 poems a day, becoming annoyed if she was disrupted. Her work rhymed but the content was banal if a touch wistful – a style her husband described as doggerel (see "Unstoppable creativity"). About six months after her seizures stopped, the desire to write became less strong, although it still persists to some extent. Doctors call the intense desire to write hypergraphia. It typically occurs alongside schizophrenia and an individual's output is usually rambling and disorganised. "It was highly unusual to see such highly structured and creative hypergraphia without any of the other behavioural disturbances," says the woman's neurologist, Jason Warren at University College London. © Copyright Reed Business Information Ltd

Keyword: Epilepsy; Language
Link ID: 20099 - Posted: 09.22.2014

I’m an epileptic. It’s not how I define myself, but I am writing about epilepsy, so I think pointing out the fact that I am speaking from experience is acceptable. I may not define myself by my epilepsy but it’s a big part of my life. It affects my life on a daily basis. Because of the epilepsy I can’t drive, can’t pull all-nighters or get up really early just in case I have a seizure. It’s frustrating at times, though I will gladly milk the not getting up early thing when I can, eg bin day. But whereas I’ve grown up with it, having been diagnosed when I was 17, most people I’ve met don’t understand it. You mention the fact that you’re epileptic to some people and they look at you like they’re a robot you’ve just asked to explain the concept of love; they adopt a sort of “DOES NOT COMPUTE!” expression. They often don’t know what to say, or do, or even what epilepsy is and often spend the rest of the conversation searching their data banks for information on what to do if I have a seizure, like “Do I … put a spoon in his mouth?” For the record: no, you don’t. If putting a spoon in an epileptics mouth helped, then we would be prescribed a constant supply of Fruit Corners. So let me put you at ease. No one expects you to know that much about epilepsy (unless you’re responsible for treating it). There are many different types, with many different causes. Not everyone has seizures and often those who do, when given the correct meds, can live pretty much fit-free lives. © 2014 Guardian News and Media Limited

Keyword: Epilepsy
Link ID: 20091 - Posted: 09.18.2014


Keyword: Epilepsy; Neuroimmunology
Link ID: 20089 - Posted: 09.18.2014


Keyword: Miscellaneous
Link ID: 19891 - Posted: 07.29.2014

By Kelly Clancy In one important way, the recipient of a heart transplant ignores its new organ: Its nervous system usually doesn’t rewire to communicate with it. The 40,000 neurons controlling a heart operate so perfectly, and are so self-contained, that a heart can be cut out of one body, placed into another, and continue to function perfectly, even in the absence of external control, for a decade or more. This seems necessary: The parts of our nervous system managing our most essential functions behave like a Swiss watch, precisely timed and impervious to perturbations. Chaotic behavior has been throttled out. Or has it? Two simple pendulums that swing with perfect regularity can, when yoked together, move in a chaotic trajectory. Given that the billions of neurons in our brain are each like a pendulum, oscillating back and forth between resting and firing, and connected to 10,000 other neurons, isn’t chaos in our nervous system unavoidable? The prospect is terrifying to imagine. Chaos is extremely sensitive to initial conditions—just think of the butterfly effect. What if the wrong perturbation plunged us into irrevocable madness? Among many scientists, too, there is a great deal of resistance to the idea that chaos is at work in biological systems. Many intentionally preclude it from their models. It subverts computationalism, which is the idea that the brain is nothing more than a complicated, but fundamentally rule-based, computer. Chaos seems unqualified as a mechanism of biological information processing, as it allows noise to propagate without bounds, corrupting information transmission and storage. © 2014 Nautilus,

Keyword: Biological Rhythms
Link ID: 19859 - Posted: 07.21.2014

Sam McDougle By now, perhaps you’ve seen the trailer for the new sci-fi thriller Lucy. It starts with a flurry of stylized special effects and Scarlett Johansson serving up a barrage of bad-guy beatings. Then comes Morgan Freeman, playing a professorial neuroscientist with the obligatory brown blazer, to deliver the film’s familiar premise to a full lecture hall: “It is estimated most human beings only use 10 percent of the brain’s capacity. Imagine if we could access 100 percent. Interesting things begin to happen.” Johansson as Lucy, who has been kidnapped and implanted with mysterious drugs, becomes a test case for those interesting things, which seem to include even more impressive beatings and apparently some kind of Matrix-esque time-warping skills. Of course, the idea that “you only use 10 percent of your brain” is, indeed, 100 hundred percent bogus. Why has this myth persisted for so long, and when is it finally going to die? Unfortunately, not any time soon. A survey last year by The Michael J. Fox Foundation for Parkinson's Research found that 65 percent of Americans believe the myth is true, 5 percent more than those who believe in evolution. Even Mythbusters, which declared the statistic a myth a few years ago, further muddied the waters: The show merely increased the erroneous 10 percent figure and implied, incorrectly, that people use 35 percent of their brains. The idea that swaths of the brain are stagnant pudding while one section does all the work is silly. Like most legends, the origin of this fiction is unclear, though there are some clues. © 2014 by The Atlantic Monthly Group

Keyword: Brain imaging
Link ID: 19848 - Posted: 07.17.2014

By Tanya Lewis and Live Science They say laughter is the best medicine. But what if laughter is the disease? For a 6-year-old girl in Bolivia who suffered from uncontrollable and inappropriate bouts of giggles, laughter was a symptom of a serious brain problem. But doctors initially diagnosed the child with “misbehavior.” “She was considered spoiled, crazy — even devil-possessed,” José Liders Burgos Zuleta of the Advanced Medical Image Centre in La Paz said in a statement. [ But Burgos Zuleta discovered that the true cause of the girl’s laughing seizures, medically called gelastic seizures, was a brain tumor. After the girl underwent a brain scan, the doctors discovered a hamartoma, a small, benign tumor that was pressing against her brain’s temporal lobe. Surgeons removed the tumor, the doctors said. She stopped having the uncontrollable attacks of laughter and now laughs only normally, they said. Gelastic seizures are a relatively rare form of epilepsy, said Solomon Moshé, a pediatric neurologist at Albert Einstein College of Medicine in New York. “It’s not necessarily ‘ha-ha-ha’ laughing,” Moshé said. “There’s no happiness in this. Some of the kids may be very scared,” he added. The seizures are most often caused by tumors in the hypothalamus, although they can also come from tumors in other parts of brain, Moshé said. Although laughter is the main symptom, patients may also have outbursts of crying.

Keyword: Emotions; Epilepsy
Link ID: 19765 - Posted: 06.24.2014

In a new study, scientists at the National Institutes of Health took a molecular-level journey into microtubules, the hollow cylinders inside brain cells that act as skeletons and internal highways. They watched how a protein called tubulin acetyltransferase (TAT) labels the inside of microtubules. The results, published in Cell, answer long-standing questions about how TAT tagging works and offer clues as to why it is important for brain health. Microtubules are constantly tagged by proteins in the cell to designate them for specialized functions, in the same way that roads are labeled for fast or slow traffic or for maintenance. TAT coats specific locations inside the microtubules with a chemical called an acetyl group. How the various labels are added to the cellular microtubule network remains a mystery. Recent findings suggested that problems with tagging microtubules may lead to some forms of cancer and nervous system disorders, including Alzheimer’s disease, and have been linked to a rare blinding disorder and Joubert Syndrome, an uncommon brain development disorder. “This is the first time anyone has been able to peer inside microtubules and catch TAT in action,” said Antonina Roll-Mecak, Ph.D., an investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and the leader of the study. Microtubules are found in all of the body’s cells. They are assembled like building blocks, using a protein called tubulin. Microtubules are constructed first by aligning tubulin building blocks into long strings. Then the strings align themselves side by side to form a sheet. Eventually the sheet grows wide enough that it closes up into a cylinder. TAT then bonds an acetyl group to alpha tubulin, a subunit of the tubulin protein.

Keyword: Miscellaneous
Link ID: 19729 - Posted: 06.14.2014