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

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Sara Reardon Manipulating brain circuits with light and drugs can cause ripple effects that could muddy experimental results. In the tightly woven networks of the brain, tugging one neuronal thread can unravel numerous circuits. Because of that, the authors of a paper1 published in Nature on 9 December caution that techniques such as optogenetics — activating neurons with light to control brain circuits — and manipulation with drugs could lead researchers to jump to unwarranted conclusions. In work with rats and zebra finches, neuroscientist Bence Ölveczky of Harvard University in Cambridge, Massachusetts, and his team found that stimulating one part of the brain to induce certain behaviours might cause other, unrelated parts to fire simultaneously, and so make it seem as if these circuits are also involved in the behaviour. According to Ölveczky, the experiments suggest that although techniques such as optogenetics may show that a circuit can perform a function, they do not necessarily show that it normally performs that function. “I don’t want to say other studies have been wrong, but there is a danger to overinterpreting,” he says. Ölveczky and his colleagues discovered these discrepancies by chance while studying rats that they had trained to press a lever in a certain pattern. They injected a drug called muscimol, which temporarilty shuts off neurons, into a part of the motor cortex that is involved in paw movement. The animals were no longer able to perform the task, which might be taken as evidence that neurons in this brain region were necessary to its performance. © 2015 Nature Publishing Group

Keyword: Brain imaging
Link ID: 21690 - Posted: 12.10.2015

Angus Chen Parents of children with severe epilepsy have reported incredible recoveries when their children were given cannabidiol, a derivative of marijuana. The drug, a non-psychoactive compound that occurs naturally in cannabis, has been marketed with epithets like Charlotte's Web and Haleigh's Hope. But those parents were taking a risk; there has been no clinical data on cannabidiol's safety of efficacy as an anti-epileptic. This week, doctors are presenting the first studies trying to figure out if cannabidiol actually works. They say the studies' results are promising, but with a grain of salt. The largest study being presented at the American Epilepsy Society meeting in Philadelphia this week was started in 2014 with 313 children from 16 different epilepsy centers around the country. Over the course of the three-month trial, 16 percent of the participants withdrew because the cannabidiol was either ineffective or had adverse side-effects, says Dr. Orrin Devinsky, a neurologist at the New York University Langone Medical Center and lead author on the study. But for the 261 patients that continued taking cannabidiol, the number of convulsive seizures, called grand mal or tonic-clonic seizures, went down by about half on average. Devinsky says that some children continued to experience benefits on cannabidiol after the trial ended. "In the subsequent periods, which are very encouraging, 9 percent of all patients and 13 percent of those with Dravet Syndrome epilepsy were seizure-free. Many have never been seizure-free before," he says. It's one of several [at least four. checking] papers on cannabidiol being presented this week at the American Epilepsy Society meeting in Philadelphia. © 2015 npr

Keyword: Epilepsy; Drug Abuse
Link ID: 21680 - Posted: 12.08.2015

A woman born incapable of feeling pain has been hurt for the first time – thanks to a drug normally prescribed for opioid overdoses. She was burned with a laser, and quite liked the experience. The breakthrough may lead to powerful new ways to treat painful conditions such as arthritis. Only a handful people around the world are born unable to feel pain. These individuals can often suffer a range of injuries when they are young. Babies with the condition tend to chew their fingers, toes and lips until they bleed, and toddlers can suffer an increased range of knocks, tumbles and encounters with sharp or hot objects. The disorder is caused by a rare genetic mutation that results in a lack of ion channels that transport sodium across sensory nerves. Without these channels, known as Nav1.7 channels, nerve cells are unable to communicate pain. Researchers quickly sought to make compounds that blocked Nav1.7 channels, thinking they might be able to block pain in people without the disorder. “It looked like a fantastic drug target,” says John Wood at University College London. “Pharma companies went bananas and made lots of drugs.” But while a few compounds saw some success, none brought about the total pain loss seen in people who lack the channel naturally. © Copyright Reed Business Information Ltd.

Keyword: Pain & Touch; Genes & Behavior
Link ID: 21677 - Posted: 12.05.2015

Laura Sanders Taking a pregnancy hormone staves off multiple sclerosis relapses, a small clinical trial suggests. The results hint at a potential therapy for women who suffer from MS, a debilitating disease in which the body’s immune system attacks the insulation that wraps around nerve cell fibers. A curious observation kicked off this line of research: Pregnancy offers a temporary reprieve for women with MS. Since that discovery, in the 1990s, scientists have been testing whether certain pregnancy hormones might combat MS in women who aren’t pregnant. In addition to a standard MS drug, 164 women with MS received either a placebo or estriol, an estrogen made by the placenta that peaks toward the end of pregnancy. After two years, women who received estriol had an average of 0.25 relapses a year, while women who received the placebo had 0.37 relapses a year, UCLA neurologist Rhonda Voskuhl and colleagues write online November 24 in Lancet Neurology. Researchers don’t know whether estriol would have similar effects in men with MS. The results warrant a larger clinical trial, the authors say. An accompanying commentary in the same issue of Lancet Neurology questions the results, though. MS specialist Annette Langer-Gould of Kaiser Permanente in Pasadena, Calif., raises methodological issues and writes that pregnancy comes with a host of changes that could be responsible for protection from MS. © Society for Science & the Public 2000 - 2015.

Keyword: Multiple Sclerosis; Hormones & Behavior
Link ID: 21674 - Posted: 12.03.2015

By Seth Fletcher To solve the mysteries of the brain, scientists need to delicately, precisely monitor neurons in living subjects. Brain probes, however, have generally been brute-force instruments. A team at Harvard University led by chemist Charles Lieber hopes that silky soft polymer mesh implants will change this situation. So far the researchers have tested the mesh, which is embedded with electronic sensors, in living mice. Once it has been proved safe, it could be used in people to study how cognition arises from the action of individual neurons and to treat diseases such as Parkinson's. © 2015 Scientific American

Keyword: Brain imaging
Link ID: 21645 - Posted: 11.20.2015

By Simon Makin Optogenetics is probably the biggest buzzword in neuroscience today. It refers to techniques that use genetic modification of cells so they can be manipulated with light. The net result is a switch that can turn brain cells off and on like a bedside lamp. The technique has enabled neuroscientists to achieve previously unimagined feats and two of its inventors—Karl Deisseroth of Stanford University and the Howard Hughes Medical Institute and Ed Boyden of Massachusetts Institute of Technology—received a Breakthrough Prize in the life sciences on November 8 in recognition of their efforts. The technology is able to remotely control motor circuits—one example is having an animal run in circles at the flick of a switch. It can even label and alter memories that form as a mouse explores different environments. These types of studies allow researchers to firmly establish a cause-and-effect relationship between electrical activity in specific neural circuits and various aspects of behavior and cognition, making optogenetics one of the most widely used methods in neuroscience today. As its popularity soars, new tricks are continually added to the optogenetic arsenal. The latest breakthroughs, promise to deliver the biggest step forward for the technology since its inception. Researchers have devised ways of broadening optogenetics to enter into a dynamic dialogue with the signals moving about inside functioning brains. © 2015 Scientific American

Keyword: Brain imaging
Link ID: 21621 - Posted: 11.10.2015

Susan Milius Electric eels are even more shocking than biologists thought. When prey fights back, eels just — curl their tails. Muscle has evolved “into a battery” independently in two groups of fishes, explains Kenneth Catania of Vanderbilt University in Nashville. Smaller species send out slight tingles of electric current that detect the fish’s surroundings in murky nighttime water. People can handle these small fishes and not feel even a tickle. But touching the bigger Electrophorus electricus (a member of a South American group of battery-included fishes)“is reminiscent of walking into an electric fence on a farm,” Catania says. (He knows, unintentionally, from experience.) The modified muscle that works as an electricity-generating organ in the eel has just on/off power. But eels have a unique way of intensifying the effect, Catania reports October 28 in Current Biology. Catania has tussled with eels using what he calls his electric eel chew toy — a dead fish on a stick with electrodes inside the carcass to measure current. When fighting difficult prey Iike the recalcitrant toy, eels curl their tails toward the fish struggling in their jaws. This bend puts the electrically negative tail-end of the long battery organ closer to the electrically positive front end, effectively concentrating the electric field on the prey. An eel’s tail curl can double the strength of the electric field convulsing the prey. © Society for Science & the Public 2000 - 2015.

Keyword: Animal Communication; Aggression
Link ID: 21581 - Posted: 10.29.2015

Fragment of rat brain simulated in supercomputer Moheb Costandi A controversial European neuroscience project that aims to simulate the human brain in a supercomputer has published its first major result: a digital imitation of circuitry in a sandgrain-sized chunk of rat brain. The work models some 31,000 virtual brain cells connected by roughly 37 million synapses. The goal of the Blue Brain Project, which launched in 2005 and is led by neurobiologist Henry Markram of the Swiss Federal Institute of Technology in Lausanne (EPFL), is to build a biologically-detailed computer simulation of the brain based on experimental data about neurons' 3D shapes, their electrical properties, and the ion channels and other proteins that different cell types typically produce (see ‘Brain in a box’). Such a simulation would provide deep insights into the way the brain works, says Markram. But other neuroscientists have argued that it will reveal no more about the brain’s workings than do simpler, more abstract simulations of neural circuitry — while sucking up a great deal of computing power and resources. The initiative has links with the Human Brain Project, a €1-billion (US$1.1-billion), decade-long initiative which Markram helped persuade the European Commission to fund, and which also aims to advance supercomputer brain simulation. It launched in 2013, with Markram as co-leader, although this March its leadership was switched and its scientific programme altered, after criticism of the way it was being managed. © 2015 Nature Publishing Group

Keyword: Brain imaging
Link ID: 21494 - Posted: 10.09.2015

A new drug for multiple sclerosis can cut relapses by almost 50% more than the current standard treatment, its manufacturer claims, raising the hopes of sufferers of the disease. The Swiss pharmaceutical giant Roche announced the headline results for its drug, ocrelizumab, but has not published the detailed outcome of its trials. The announcement was warmly welcomed by patients, not least because Roche claims the drug also has an impact on a form of the disease, called primary-progressive, which affects 10-15% of people with MS in the UK and for which there are no treatments. Roche claimed it cut disability in those patients by nearly a quarter. “These phase three trial results will provide a great deal of hope for people with primary-progressive MS, who currently don’t have any treatments available that can slow down the worsening of their condition,” said Nick Rijke, the MS Society’s executive director for policy and research. “Finding effective treatments for multiple sclerosis is our number one priority at the MS Society and this is a big moment. The drug was compared in the trials with Rebif, an established drug made by Merck that reduces relapses by about a third. Ocrelizumab – which does not yet have a brand name – was said to cut annual relapses by 46% and 47% compared with Rebif in the two trials. The biggest advantage, however, may be that it is claimed to cause fewer side effects than the established drug. © 2015 Guardian News and Media Limited

Keyword: Multiple Sclerosis; Neuroimmunology
Link ID: 21490 - Posted: 10.09.2015

by Sarah Schwartz People with multiple sclerosis who got less sun exposure and had higher body mass as young adults developed the disease sooner than those who spent more time in the sun and were a normal weight, a new study finds. In a study of over 1,100 Danish people with MS — a nervous system condition that causes muscle weakness and pain — patients who were overweight at age 20 developed multiple sclerosis an average of 1.5 years sooner than patients of normal weight. And subjects who reported spending time in the sun every summer’s day during adolescence developed the disease 1.8 years later, on average, than patients who got less sun exposure, Danish researchers report online October 7 in Neurology. The results echo earlier work that found a link between adolescent obesity and risk of MS. And sun exposure may increase patients’ levels of vitamin D, which has been shown to protect against the disease, the researchers say. © Society for Science & the Public 2000 - 2015

Keyword: Multiple Sclerosis; Biological Rhythms
Link ID: 21486 - Posted: 10.08.2015

James Gorman Turning certain brain cells on and off with light — a technique called optogenetics — is one of the most important tools in neuroscience. It allows scientists to test basic ideas about how brains work. But because waves of visible light don’t penetrate living tissue well, the technique requires the insertion of a conduit for the light into the brain— a very thin fiber optic cable. For the first time, researchers say, they have done the same with ultrasound, opening the way to a noninvasive way to probe the functions of neurons. They call the technique sonogenetics. They achieved this in a microscopic worm, a creature so simple that it doesn’t have a brain. But it does have neurons, which have a great deal in common with the neurons in more complex animals that make up the brain and nervous system. If the technique works in more complex animals, it would mean a noninvasive way to do basic research, and perhaps even treat brain circuits. “Previous studies have shown if you use ultrasound, you can manipulate the nervous system,” said Sreekanth H. Chalasani of the Salk Institute in San Diego and senior author of a recent report in Nature Communications that describes the research. But, he said, nobody had shown that, with genetic modifications, specific neurons could be targeted. “It’s going to be a viable technique,” said William Tyler, a neuroscientist at Arizona State University, who said the ability to zero in on one neuron or a group of neurons without having to insert anything into the body was “unparalleled.” © 2015 The New York Times Company

Keyword: Brain imaging
Link ID: 21453 - Posted: 09.28.2015

By Diana Kwon Multiple sclerosis (MS) relapses are known to swing with the seasons. Scientists have attributed these fluctuations to the rise and fall of vitamin D production, which is triggered by exposure to seasonal sunlight. Now a new study suggests that melatonin, a hormone that regulates your internal body clock and sleep cycles, could also play a protective role. MS is a disease of the central nervous system in which an abnormal immune response attacks the myelin sheath, or fatty protective layer, around neurons. The resulting degradation slows signaling between the brain and the rest of the body, potentially leading to a wide variety of symptoms that include weakness, vision problems and cognitive changes. The condition may affect as many as 2.3 million people worldwide. The cause of the disease remains unknown, although researchers have started to identify genetic risks and environmental factors, including smoking, viral infections and vitamin D levels in the bloodstream. The latest environmental influence, observed by Mauricio Farez, a neuroscientist at the Raúl Carrea Institute for Neurological Research, and colleagues could involve peak melatonin levels in the body, which occur during the darker months. The researchers assessed a group of 139 multiple sclerosis patients in Buenos Aires and found a 32 percent reduction in the number of relapses in the fall and winter, when people living in the Southern Hemisphere produce more of the hormone, compared with summer and spring. The results are published on the September 10 Cell. © 2015 Scientific American

Keyword: Multiple Sclerosis; Biological Rhythms
Link ID: 21442 - Posted: 09.24.2015

Helen Shen Neuroscientists have used ultrasound to stimulate individual brain cells in a worm, and hope that the technique — which they call ‘sonogenetics’ — might be adapted to switch on neurons in mice and larger animals. The technique relies on touch-sensitive ‘channel’ proteins, which can be added to particular brain cells through genetic engineering. The channels open when hit by an ultrasonic pulse, which allows ions to flood into a neuron and so causes it to turn on. Ultrasound could be a less-invasive way for researchers to stimulate specific cell types or individual neurons, rather than using implanted electrodes or fibre-optic cables, says neurobiologist Sreekanth Chalasani, at the Salk Institute for Biological Studies in La Jolla, California, who led the study reported today in Nature Communications1. “Our hope is to create a toolbox of different channels that would each respond to different intensities of ultrasound,” he says. "It's a cool new idea, and they show that this could really be feasible," says Jon Pierce-Shimomura, a neuroscientist who studies the nematode Caenorhabditis elegans at the University of Texas at Austin. “This could open a whole new way for manipulating the nervous system non-invasively through genetically encodable tools.” © 2015 Nature Publishing Group,

Keyword: Brain imaging
Link ID: 21417 - Posted: 09.16.2015

By Sarah Schwartz Darkness and light may help prevent multiple sclerosis or fend off its symptoms. People who genetically produce less vitamin D, a compound normally boosted by sun exposure, have a greater risk of multiple sclerosis, researchers find. But the hormone melatonin, which the body produces in response to darkness, may reduce flare-ups for people who have the disease, another team of scientists reports. The studies may help researchers better understand and treat multiple sclerosis, a disease of the nervous system. It causes symptoms including muscle weakness, pain and vision loss in over 2 million people worldwide. Previous studies linked lower vitamin D levels to higher multiple sclerosis risk, but it was unclear whether this relationship was a coincidence. In work appearing August 25 in PLOS Medicine, scientists examined genetic data from thousands of Europeans and found that three genetic changes known to reduce vitamin D levels were associated with increased multiple sclerosis risk. These findings suggest that individuals with a higher risk of developing the disease, such as immediate family members of multiple sclerosis patients, should take steps to ensure they have sufficient levels of vitamin D, says study coauthor Brent Richards, a genetic epidemiologist at McGill University in Montreal. People can raise vitamin D levels to normal by taking an oral supplement. © Society for Science & the Public 2000 - 2015.

Keyword: Multiple Sclerosis; Biological Rhythms
Link ID: 21399 - Posted: 09.11.2015

By Amy Ellis Nutt Magnetic pulses from a device applied to the head appear to "reset" the brains of depressed patients, according to a new study from the United Kingdom. The circuitry in a part of the right prefrontal cortex is known to be too active in depressed patients, causing excessive rumination and self absorption and impaired attention. When the TMS was applied to healthy subjects in this study, the activity in that region slowed. "We found that one session of TMS modifies the connectivity of large-scale brain networks, particularly the right anterior insula, which is a key area in depression," lead scientist Sarina Iwabuchi, told the European College of Neuropsychology at a conference in Amsterdam this week. This was the first time an MRI was used to guide the TMS impulses and, at the same, time measure subtle changes in brain circuit activity. In addition, the researchers used magnetic resonance spectroscopy to analyze subjects' brain chemistry. "We also found that TMS alters concentrations of neurotransmitters. Iwabuchi said, "which are considered important for the development of depression," and which are the targets of most current antidepressant medications. Transcranial Magnetic Stimulation is the use of an electromagnetic coil to deliver small, powerful bursts of energy to targeted areas known to be involved in mood regulation. It is a painless, non-invasive treatment than involves no drugs, no IVs, or any other kind of sedation, and whose chief possible side effect is a headache. (The Food and Drug Administration approved limited use of TMS in 2008 for the treatment of depression.)

Keyword: Depression
Link ID: 21352 - Posted: 08.28.2015

By Michelle Roberts Health editor, BBC News online People genetically prone to low vitamin-D levels are at increased risk of multiple sclerosis, a large study suggests. The findings, based on the DNA profiles of tens of thousands of people of European descent, add weight to the theory that the sunshine vitamin plays a role in MS. Scientists are already testing whether giving people extra vitamin D might prevent or ease MS. Experts say the jury is still out. It is likely that environmental and genetic factors are involved in this disease of the nerves in the brain and spinal cord, they say. And if you think you may not be getting sufficient vitamin D from sunlight or your diet, you should discuss this with your doctor. Taking too much vitamin D can also be dangerous. Research around the world already shows MS is more common in less sunny countries, further from the equator. But it is not clear if this relationship is causal - other factors might be at play. To better understand the association, investigators at McGill University in Canada compared the prevalence of MS in a large group of Europeans with and without a genetic predisposition to low vitamin D. © 2015 BBC.

Keyword: Multiple Sclerosis
Link ID: 21339 - Posted: 08.26.2015

Alison Abbott This is the crackle of neural activity that allows a fruit-fly (Drosophila melanogaster) larva to crawl backwards: a flash in the brain and a surge that undulates through the nervous system from the top of the larva’s tiny body to the bottom. When the larva moves forwards, the surge flows the other way. The video — captured almost at the resolution of single neurons — demonstrates the latest development in a technique to film neural activity throughout an entire organism. The original method was invented by Philipp Keller and Misha Ahrens at the Howard Hughes Medical Institute's Janelia Research Campus in Ashburn, Virginia. The researchers genetically modify neurons so that each cell fluoresces when it fires; they then use innovative microscopy that involves firing sheets of light into the brain to record that activity. In 2013, the researchers produced a video of neural activity across the brain of a (transparent) zebrafish larva1. The fruit-fly larva that is mapped in the latest film, published in Nature Communications on 11 August2, is more complicated. The video shows neural activity not just in the brain, but throughout the entire central nervous system (CNS), including the fruit-fly equivalent of a mammalian spinal cord. And unlike the zebrafish, the fruit fly's nervous system is not completely transparent, which makes it harder to image. The researchers stripped the CNS from the larva’s body to examine it. For up to an hour after removal, the CNS continues to spontaneously fire the coordinated patterns of activity that typically drive crawling (and other behaviours). © 2015 Nature Publishing Group

Keyword: Brain imaging
Link ID: 21291 - Posted: 08.12.2015

Ashley Yeager A mouse scurries across a round table rimmed with Dixie cup–sized holes. Without much hesitation, the rodent heads straight for the hole that drops it into a box lined with cage litter. Any other hole would have led to a quick fall to the floor. But this mouse was more than lucky. It had an advantage — human glial cells were growing in its brain. Glia are thought of as the support staff for the brain’s nerve cells, or neurons, which transmit and receive the brain’s electrical and chemical signals. Named for the Greek term for “glue,” glia have been known for nearly 170 years as the cells that hold the brain’s bits together. Some glial cells help feed neurons. Other glia insulate nerve cell branches with myelin. Still others attack brain invaders responsible for infection or injury. Glial cells perform many of the brain’s most important maintenance jobs. But recent studies suggest they do a lot more. Glia can shape the conversation between neurons, speeding or slowing the electrical signals and strengthening neuron-to-neuron connections. When scientists coaxed human glia to grow in the brains of baby mice, the mice grew up to be supersmart, navigating tabletops full of holes and mastering other tasks much faster than normal mice. This experiment and others suggest that glia may actually orchestrate learning and memory, says neuroscientist R. Douglas Fields. “Glia aren’t doing vibrato. That’s for the neurons,” says Fields, of the National Institute of Child Health and Human Development in Bethesda, Md. “Glia are the conductors.” © Society for Science & the Public 2000 - 2015

Keyword: Learning & Memory; Glia
Link ID: 21289 - Posted: 08.12.2015

Jon Hamilton Lihong Wang creates the sort of medical technology you'd expect to find on the starship Enterprise. Wang, a professor of biomedical engineering at Washington University in St. Louis, has already helped develop instruments that can detect individual cancer cells in the bloodstream and oxygen consumption deep within the body. He has also created a camera that shoots at 100 billion frames a second, fast enough to freeze an object traveling at the speed of light. "It's really about turning some of these ideas that we thought were science fiction into fact," says Richard Conroy, who directs the Division of Applied Science & Technology at the National Institute of Biomedical Imaging and Bioengineering. Wang's ultimate goal is to use a combination of light and sound to solve the mysteries of the human brain. The brain is a "magical black box we still don't understand," he says. Wang describes himself as a toolmaker. And when President Obama unveiled his BRAIN initiative a couple of years ago to accelerate efforts to understand how we think and learn and remember, Wang realized that brain researchers really needed a tool he'd been working on for years. "We want to conquer the brain," Wang says. "But even for a mouse brain, which is only a few millimeters thick, we really don't have a technique that allows us to see throughout the whole brain." Current brain-imaging techniques such as functional MRI or PET scans all have drawbacks. They're slow, or not sharp enough, or they can only see things near the surface. So Wang has been developing another approach, one he believes will be fast enough to monitor brain activity in real time and sharp enough to reveal an individual brain cell. © 2015 NPR

Keyword: Brain imaging
Link ID: 21226 - Posted: 07.27.2015

A study showed that scientists can wirelessly determine the path a mouse walks with a press of a button. Researchers at the Washington University School of Medicine, St. Louis, and University of Illinois, Urbana-Champaign, created a remote controlled, next-generation tissue implant that allows neuroscientists to inject drugs and shine lights on neurons deep inside the brains of mice. The revolutionary device is described online in the journal Cell. Its development was partially funded by the National Institutes of Health. “It unplugs a world of possibilities for scientists to learn how brain circuits work in a more natural setting.” said Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology at Washington University School of Medicine and a senior author of the study. The Bruchas lab studies circuits that control a variety of disorders including stress, depression, addiction, and pain. Typically, scientists who study these circuits have to choose between injecting drugs through bulky metal tubes and delivering lights through fiber optic cables. Both options require surgery that can damage parts of the brain and introduce experimental conditions that hinder animals’ natural movements. To address these issues, Jae-Woong Jeong, Ph.D., a bioengineer formerly at the University of Illinois at Urbana-Champaign, worked with Jordan G. McCall, Ph.D., a graduate student in the Bruchas lab, to construct a remote controlled, optofluidic implant. The device is made out of soft materials that are a tenth the diameter of a human hair and can simultaneously deliver drugs and lights.

Keyword: Brain imaging
Link ID: 21184 - Posted: 07.18.2015