Posts tagged neuroscience
Articles and news from the latest research reports.
Neuroprosthesis gives rats the ability to ‘touch’ infrared light
Researchers have given rats the ability to “touch” infrared light, normally invisible to them, by fitting them with an infrared detector wired to microscopic electrodes implanted in the part of the mammalian brain that processes tactile information. The achievement represents the first time a brain-machine interface has augmented a sense in adult animals, said Duke University neurobiologist Miguel Nicolelis, who led the research team.
The experiment also demonstrated for the first time that a novel sensory input could be processed by a cortical region specialized in another sense without “hijacking” the function of this brain area said Nicolelis. This discovery suggests, for example, that a person whose visual cortex was damaged could regain sight through a neuroprosthesis implanted in another cortical region, he said.
Although the initial experiments tested only whether rats could detect infrared light, there seems no reason that these animals in the future could not be given full-fledged infrared vision, said Nicolelis. For that matter, cortical neuroprostheses could be developed to give animals or humans the ability to see in any region of the electromagnetic spectrum, or even magnetic fields. “We could create devices sensitive to any physical energy,” he said. “It could be magnetic fields, radio waves, or ultrasound. We chose infrared initially because it didn’t interfere with our electrophysiological recordings.”
Nicolelis and colleagues Eric Thomson and Rafael Carra published their findings February 12, 2013 in the online journal Nature Communications. Their research was sponsored by the National Institute of Mental Health.
Stopping cold: USC scientists turn off the ability to feel cold
USC neuroscientists have isolated chills at a cellular level, identifying the sensory network of neurons in the skin that relays the sensation of cold.
David McKemy, associate professor of neurobiology in the USC Dornsife College of Letters, Arts and Sciences, and his team managed to selectively shut off the ability to sense cold in mice while still leaving them able to sense heat and touch.
In prior work, McKemy discovered a link between the experience of cold and a protein known as TRPM8 (pronounced trip-em-ate), which a sensor of cold temperatures in neurons in the skin, as well as a receptor for menthol, the cooling component of mint. Now, in a paper appearing in the Journal of Neuroscience on February 13, McKemy and his co-investigators have isolated and ablated the neurons that express TRPM8, giving them the ability to test the function of these cells specifically.
Using mouse-tracking software program developed by one of McKemy’s students, the researchers tested control mice and mice without TRPM8 neurons on a multi-temperature surface. The surface temperature ranged from 0 degrees to 50 degrees Celsius (32 to 122 degrees Farenheit), and mice were allowed to move freely among the regions.
The researchers found that mice depleted of TRPM8 neurons could not feel cold, but still responded to heat. Control mice tended to stick to an area around 30 degrees Celsius (86 degrees Fahrenheit) and avoided both colder and hotter areas. But mice without TRPM8 neurons avoided only hotter plates and not cold — even when the cold should have been painful or was potentially dangerous.
In tests of grip strength, responses to touch, or coordinated movements, such as balancing onto a rod while it rotated, there was no difference between the control mice and the mice without TRPM8-expressing neurons.
By better understanding the specific ways in which we feel sensations, scientists hope to one day develop better pain treatments without knocking out all ability to feel for suffering patients.
"The problem with pain drugs now is that they typically just reduce inflammation, which is just one potential cause of pain, or they knock out all sensation, which often is not desirable," McKemy said. "One of our goals is to pave the way for medications that address the pain directly, in a way that does not leave patients completely numb."
Some Autism Behaviors Linked to Altered Gene
Scientists at Washington University School of Medicine in St. Louis have identified a genetic mutation that may underlie common behaviors seen in some people with autism, such as difficulty communicating and resistance to change.
An error in the gene, CELF6, leads to disturbances in serotonin, a chemical that relays messages in the brain and has long been suspected to be involved in autism.
The researchers identified the error in a child with autism and then, working in mice, showed that the same genetic alteration results in autism-related behaviors and a sharp drop in the level of serotonin circulating in the brain.
While the newly discovered mutation appears to be rare, it provides some of the first clues to the biological basis of the disease, the scientists report Feb. 13 in the Journal of Neuroscience.
“Genetically, autism looks very complicated, with many different genetic routes that lead to the disease,” says lead author Joseph D. Dougherty, PhD, an assistant professor of genetics at Washington University. “But it’s not possible to design a different drug for every child. The real key is to find the common biological pathways that link these different genetic routes and target those pathways for treatment.”
Autism is known to have a strong genetic component, but the handful of genes implicated in the condition so far explain only a small number of cases or make a small contribution to symptoms.
This led Dougherty and senior author Nathaniel Heintz, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, to speculate that some of the most common behavioral symptoms of autism may be caused by disruptions in a common biological pathway, like the one involved in serotonin signaling.
Research finds protein that prevents light-induced retinal degeneration
Research led by Minghao Jin, PhD, Assistant Professor of Ophthalmology and Neuroscience at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence, has found a protein that protects retinal photoreceptor cells from degeneration caused by light damage. This protein may provide a new therapeutic target for both an inherited retinal degenerative disease and age-related macular degeneration. The paper is published in the February 13, 2013 issue of the Journal of Neuroscience.
The visual cycle is essential for regenerating visual pigments that sense light for vision. However, abnormal visual cycles promote formation of toxic byproducts that contribute to the development of age-related macular degeneration (AMD), the leading cause of vision loss in elderly people that affects an estimated 2 million Americans. The mechanisms that regulate the visual cycle have been unclear. Identification and characterization of regulators of the visual cycle enzymes are critical for understanding these mechanisms.
RPE65 is a key enzyme involved in the visual cycle. RPE65 mutations have been linked to early onset vision loss, retinal degeneration, and blinding eye diseases. Despite such importance, the mechanisms that regulate the function of RPE65 are unknown. To identify and characterize previously unknown inhibitors of RPE65, the scientists tested five candidate proteins. Using gene screening, the LSUHSC research team discovered that one of them – fatty acid transport protein 4 (FATP4) – is a negative regulator; it inhibits RPE65.
"We found that FATP4 protects retinal photoreceptor cells from experimentally-induced retinal degeneration," notes Nicolas Bazan, MD, PhD, Boyd Professor, Ernest C. and Yvette C. Villere Endowed Chair of Retinal Degeneration, and Director of the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence, who is a co-author of the paper.
Recently, mutations in the human FATP4 gene have been identified in patients with a certain recessive disorder which also features one of the toxic byproducts associated with abnormal visual cycles. This byproduct, called A2E accumulates in retinal pigment epithelial cells with age, prompting a call for further investigation to determine whether FATP4 mutations cause age-related vision impairment and retinal degeneration.
"These findings suggest that FATP4 may be a therapeutic target for the inherited retinal degenerative disease caused by RPE65 mutations and AMD," concludes Dr. Jin.
(Image: Eyeland Design Network)
Long memories in brain activity explain streaks in individual behaviour
Even with a constant task, human performance fluctuates in time-scales from seconds to minutes in a fractal manner. In a recent study a Finnish research group found that the individual variability in the brain dynamics as indexed by the neuronal scaling laws predicted the individual behavioral variability and the conscious detection of very weak sensory stimuli. These data indicate that individual neuronal dynamics underlie the individual variability in human cognition and performance. Results may also have a strong impact in understanding the neuronal mechanism of neuropsychiatric diseases in which behavioral dynamics are abnormal.
Human performance in cognitive tasks varies from moment-to-moment so that the similar behavioral performance is clustered into streaks. The neuronal dynamics underlying this behavioral variability has remained unknown.
Similar scale-free and power-law distributed “avalanche dynamics” is observed in many natural systems such as sand piles, earthquakes, gene regulation, and also brain activity. However, the functional significance of the neuronal scale-free behavior has remained unknown. It is also unclear whether it is just epiphenomena without any further significance.
"We investigated whether the individual variability in the scaling-laws governing the detection of auditory and visual stimuli presented in the threshold of detection could be predicted by the variability in the neuronal scaling laws", explains Matias Palva, project leader in the Neuroscience Center of the University of Helsinki, Finland.
The researchers used magneto- and electroencephalography to record non-invasively human brain activity during the task performance. They found that both the behavioral and neuronal dynamics were characterized by scale-free dynamics. Individual variability in the neuronal scaling laws predicted the individual scaling laws in behavioral performance.
"These results suggest that the individual behavioral and psychophysical variability in task performance is largely a result of the inherent variability in the individual neuronal dynamics", says project leader Satu Palva.
(Image: Harry Sieplinga, HMS/Getty Images)
Early music lessons boost brain development
If you started piano lessons in grade one, or played the recorder in kindergarten, thank your parents and teachers. Those lessons you dreaded – or loved – helped develop your brain. The younger you started music lessons, the stronger the connections in your brain.
A study published last month in the Journal of Neuroscience suggests that musical training before the age of seven has a significant effect on the development of the brain, showing that those who began early had stronger connections between motor regions – the parts of the brain that help you plan and carry out movements.
This research was carried out by students in the laboratory of Concordia University psychology professor Virginia Penhune, and in collaboration with Robert J. Zatorre, a researcher at the Montreal Neurological Institute and Hospital at McGill University.
The study provides strong evidence that the years between ages six and eight are a “sensitive period” when musical training interacts with normal brain development to produce long-lasting changes in motor abilities and brain structure. “Learning to play an instrument requires coordination between hands and with visual or auditory stimuli,” says Penhune. “Practicing an instrument before age seven likely boosts the normal maturation of connections between motor and sensory regions of the brain, creating a framework upon which ongoing training can build.”
Potential treatment prevents damage from prolonged seizures
A new type of prophylactic treatment for brain injury following prolonged epileptic seizures has been developed by Emory University School of Medicine investigators.
Status epilepticus, a persistent seizure lasting longer than 30 minutes [check this, some people say FIVE], is potentially life-threatening and leads to around 55,000 deaths each year in the United States. It can be caused by stroke, brain tumor or infection as well as inadequate control of epilepsy. Physicians or paramedics now treat status epilepticus by administering an anticonvulsant or general anesthesia, which stops the seizures.
Researchers at Emory have been looking for something different: anti-inflammatory compounds that can be administered after acute status epilepticus has ended to reduce damage to the brain. They have discovered a potential lead compound that can reduce mortality when given to mice after drug-induced seizures.
The results are scheduled for publication Monday in Proceedings of the National Academy of Sciences Early Edition.
"For adults who experience a period of status epilepticus longer than one hour, more than 30 percent die within four weeks of the event, making this a major medical problem," says Ray Dingledine, PhD, chair of the Department of Pharmacology at Emory University School of Medicine. "Medications that would reduce the severe consequences of refractory status epilepticus have been elusive. We believe we have an effective route to minimizing the brain injury caused by uncontrolled status epilepticus."
Dingledine’s laboratory has identified compounds that block the effects of prostaglandin E2, a hormone involved in processes such as fever, childbirth, digestion and blood pressure regulation. Prostaglandin E2 is also involved in the toxic inflammation in the brain arising after status epilepticus.
The first author of the paper is postdoctoral fellow Jianxiong Jiang, PhD, and the medicinal chemist largely responsible for developing the compounds is Thota Ganesh, PhD.
Jiang and colleagues induced status epilepticus in mice with the alkaloid drug pilocarpine, and gave them a compound, TG6-10-1, starting four hours later and again at 21 and 30 hours. TG6-10-1 blocks signals from EP2, one of four receptors for prostaglandin E2.
Among animals that received the EP2 blocker, 90 percent survived after one week, while 60 percent of a control group survived. The scientists also used nest-building behavior and weight loss as gauges of damage to the brain. Four days after status epilepticus, all the animals that received TG6-10-1 displayed normal nest-building, but more than a quarter of living control animals were not able to build nests. In addition, the brains of TG6-10-1-treated mice had reduced levels of inflammatory messenger proteins called cytokines, less brain injury and less breach of the blood-brain-barrier.
Consequences of refractory status epilepticus can include brain damage, difficulty breathing, abnormal heart rhythms and heart failure.
Dingledine says the first clinical test of an EP2 blocking compound would probably be as an add-on treatment for prolonged status epilepticus, several hours after seizures have ended. It could also be tested in similar situations such as subarachnoid hemorrhage, prolonged febrile seizures or medication-resistant epilepsy, he says.
Dingledine and his colleagues have a patent pending for novel technology related to this research. Under Emory policies, they are eligible to receive a portion of any royalties or fees received by Emory from this technology.
(Source: eurekalert.org)
Vascular brain injury greater risk factor than amyloid plaques in cognitive aging
Vascular brain injury from conditions such as high blood pressure and stroke are greater risk factors for cognitive impairment among non-demented older people than is the deposition of the amyloid plaques in the brain that long have been implicated in conditions such as Alzheimer’s disease, a study by researchers at the Alzheimer’s Disease Research Center at UC Davis has found.
Published online early today in JAMA Neurology (formerly Archives of Neurology), the study found that vascular brain injury had by far the greatest influence across a range of cognitive domains, including higher-level thinking and the forgetfulness of mild cognitive decline.
The researchers also sought to determine whether there was a correlation between vascular brain injury and the deposition of beta amyloid (Αβ) plaques, thought to be an early and important marker of Alzheimer’s disease, said Bruce Reed, associate director of the UC Davis Alzheimer’s Disease Research Center in Martinez, Calif. They also sought to decipher what effect each has on memory and executive functioning.
“We looked at two questions,” said Reed, professor in the Department of Neurology at UC Davis. “The first question was whether those two pathologies correlate to each other, and the simple answer is ‘no.’ Earlier research, conducted in animals, has suggested that having a stroke causes more beta amyloid deposition in the brain. If that were the case, people who had more vascular brain injury should have higher levels of beta amyloid. We found no evidence to support that.”
"The second,” Reed continued, “was whether higher levels of cerebrovascular disease or amyloid plaques have a greater impact on cognitive function in older, non-demented adults. Half of the study participants had abnormal levels of beta amyloid and half vascular brain injury, or infarcts. It was really very clear that the amyloid had very little effect, but the vascular brain injury had distinctly negative effects.”
“The more vascular brain injury the participants had, the worse their memory and the worse their executive function – their ability to organize and problem solve,” Reed said.
The research was conducted in 61 male and female study participants who ranged in age from 65 to 90 years old, with an average age of 78. Thirty of the participants were clinically “normal,” 24 were cognitively impaired and seven were diagnosed with dementia, based on cognitive testing. The participants had been recruited from Northern California between 2007 to 2012.
The study participants underwent magnetic resonance imaging (MRI) ― to measure vascular brain injury ― and positron emission tomography (PET) scans to measure beta amyloid deposition: markers of the two most common pathologies that affect the aging brain. Vascular brain injury appears as brain infarcts and “white matter hyperintensities” in MRI scans, areas of the brain that appear bright white.
The study found that both memory and executive function correlated negatively with brain infarcts, especially infarcts in cortical and sub-cortical gray matter. Although infarcts were common in this group, the infarcts varied greatly in size and location, and many had been clinically silent. The level of amyloid in the brain did not correlate with either changes in memory or executive function, and there was no evidence that amyloid interacted with infarcts to impair thinking.
Reed said the study is important because there’s an enormous amount of interest in detecting Alzheimer’s disease at its earliest point, before an individual exhibits clinical symptoms. It’s possible to conduct a brain scan and detect beta amyloid in the brain, and that is a very new development, he said.
“The use of this diagnostic tool will become reasonably widely available within the next couple of years, so doctors will be able to detect whether an older person has abnormal levels of beta amyloid in the brain. So it’s very important to understand the meaning of a finding of beta amyloid deposition,” Reed said.
“What this study says is that doctors should think about this in a little more complicated way. They should not forget about cerebrovascular disease, which is also very common in this age group and could also cause cognitive problems. Even if a person has amyloid plaques, those plaques may not be the cause of their mild cognitive symptoms.”
(Source: ucdmc.ucdavis.edu)
Genes for autism and schizophrenia only active in developing brains
Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a collaboration between researchers at Imperial College London, the University of Oxford and King’s College London.
This new study adds to the evidence that autism and schizophrenia are neurodevelopmental disorders, a term describing conditions that originate during early brain development.
The researchers studied gene expression in the brains of mice throughout their development, from 15-day old embryos to adults, and their results are published in Proceedings of the National Academy of Sciences.
The research focused on cells in the ‘subplate’, a region of the brain where the first neurons (nerve cells) develop. Subplate neurons are essential to brain development, and provide the earliest connections within the brain.
'The subplate provides the scaffolding required for a brain to grow, so is important to consider when studying brain development,' says Professor Zoltán Molnár, senior author of the paper from the University of Oxford, 'Looking at the pyramids in Egypt today doesn't tell us how they were actually built. Studying adult brains is like looking at the pyramids today, but by studying the developing brains we are able to see the transient scaffolding that has been used to construct it.'
The study shows that certain genes linked to autism and schizophrenia are only active in the subplate during specific stages of development. The data analysis was designed by Dr Enrico Petretto, Senior Lecturer in Genomic Medicine at Imperial College London. Dr Petretto said: “We looked at the full network of genes in the brain to identify which pathways play a role in early brain development. This allowed us to find coherent clusters of genes previously associated with susceptibility to autism spectrum disorders or schizophrenia. These results provide a unique resource for our understanding of how gene behaviour changes in the mouse subplate from the early embryonic stage to adulthood. This means we are better equipped to investigate how the gene network changes in the developing brain and identify any links with neurodevelopmental disorders.”
The team was able to map gene activity in full detail thanks to these new methods which allowed them to dissect and profile gene expression from small numbers of cells. This also enabled them to identify the different populations of subplate neurons more accurately.
Professor Hugh Perry, chair of the Medical Research Council’s Neuroscience and Mental Health Board, said: “By being able to pinpoint common genetic factors for neurological conditions such as autism and schizophrenia, scientists are able to understand an important part of the story as to why things go awry as our brains develop. The Medical Research Council’s commitment to a broad portfolio of neuroscience and mental health research places us in a unique position to respond to the challenge of mental ill health and its relationship with physical health and wellbeing.”
(Source: www3.imperial.ac.uk)
Gene gives motor neurone disease insight
A discovery using stem cells from a patient with motor neurone disease could help research into treatments for the condition.
The study used a patient’s skin cells to create motor neurons - nerve cells that control muscle activity - and the cells that support them called astrocytes.
Astrocyte death
Researchers studied these two types of cells in the laboratory. They found that a protein expressed by abnormalities in a gene linked to motor neurone disease, which is called TDP-43, caused the astrocytes to die.
The study, led by the University of Edinburgh and funded by the Motor Neurone Disease Association, provides fresh insight into the mechanisms involved in the disease.
Gene mutation
Although TDP-43 mutations are a rare cause of motor neurone disease (MND), scientists are especially interested in the gene because in the vast majority of MND patients, TDP-43 protein (made by the TDP-43 gene) forms pathological clumps inside motor neurons.
Motor neurones die in MND leading to paralysis and early death.
This study shows for the first time that abnormal TDP-43 protein causes death of astrocytes.
The researchers, however, found that the damaged astrocytes were not directly toxic to motor neurons.
Motor neurone disease is a devastating and ultimately fatal condition, for which there is no cure or effective treatment. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
Implications
Better understanding the role of astrocytes could help to inform research into treatments for motor neurone disease (MND).
These findings, published in the journal Proceedings of the National Academy of Sciences, are significant as they show that different mechanisms are at work in different types of MND.
It is not just a question of looking solely at motor neurons, but also the cells that surround them, to understand why motor neurones die. Our aim is to find ways to slow down progression of this devastating disease and ultimately develop a cure. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
(Source: ed.ac.uk)