A bizarre twist on the usual way proteins are made may explain mysterious symptoms in the grandparents of some children with mental disabilities.
The discovery, made by a team of scientists at the University of Michigan Medical School, may lead to better treatments for older adults with a recently discovered genetic condition.
The condition, called Fragile X-associated Tremor Ataxia Syndrome (FXTAS), causes shakiness and balance problems and is often misdiagnosed as Parkinson’s disease. The grandchildren of people with the disease have a separate disorder called Fragile X syndrome, caused by problems in the same gene. The new discovery may also help shine light on that disease, though indirectly.
In a new paper published in the journal Neuron, the U-M-led team presents evidence that a toxic protein they’ve named FMRpolyG contributes to the death of nerve cells in FXTAS – and that this protein is made in a very unusual way.
Normally, DNA is transcribed into RNA, and then a part of the RNA is translated into a protein that performs its function in cells. Where this translation process starts on the RNA is usually determined by a specific sequence called a start codon.
The gene mutation that causes FXTAS is a repeated DNA sequence that is made into RNA but normally is not made into protein because it lacks a start codon. However, the investigators discovered that when this repeat expands, it can trigger protein production by a new mechanism known as RAN translation.
Corresponding author Peter Todd, M.D., Ph.D., notes that this unusual translation process appears to stem from a long chain of repeated DNA “letters” found in the genes of both grandparents and kids with Fragile X mutations. Todd is the Bucky and Patti Harris Professor in the U-M Department of Neurology
"Essentially, we’ve found that a sequence of DNA which shouldn’t be made into protein is being made into protein – and that this causes a toxicity in nerve cells," he explains. "We believe that the protein forms aggregates, and that this is a major contributor to toxicity and symptoms in FXTAS."
The U-M group went on to show how this RAN translation occurs in FXTAS and demonstrated that blocking it prevents the repeat mutation from being toxic, suggesting a new target for future treatments.
Fragile X tremor/ataxia syndrome or FXTAS was only discovered a decade ago. It may affect as many as one in every 3,000 men and one in 20,000 women, who have a repeat mutation in the gene known as FMR1. However, these patients don’t usually develop symptoms until late middle age, allowing them to pass the mutation on to their daughters, who can then have children where the DNA repeat that has grown much longer. In those children, especially in boys, it can cause severe intellectual disability and autism-like symptoms as the FMR1 gene shuts down and none of the normal protein is produced.
In fact, says Todd, it’s often only after a child is diagnosed with Fragile X syndrome through genetic testing that their grandfather or grandmother finds out that their own symptoms stem from FXTAS. Doctors in U-M’s Neurogenetics clinic for adults, and the Pediatric Genetics Clinic at U-M’s C.S. Mott Children’s Hospital, routinely work together to address the needs of Fragile X families.
"We have some treatments for the symptoms that FXTAS patients have, but we do not yet have a cure," says Todd, who regularly sees patients with FXTAS and related disorders. "Better treatments are needed – and this new discovery might help lead to novel strategies for clearing away or preventing the buildup of this toxic protein."
In addition, he says, the discovery that Fragile X ataxia results in part from RAN translation could have significance both for other diseases like amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease) and certain forms of dementia that are caused by DNA repeats. It can also aid our understanding of basic biology. “This may represent a new way in which translational initiation events occur, and may have importance beyond this one disease,” he notes. Further research on how RAN translation occurs, and why, is needed.
The idea that proteins can be created without a “start site” flies in the face of what most students of biology have learned in the last century. “In biology, we’re finding that the rules we once thought were hard and fast have some wiggle room,” Todd says.
(Source: eurekalert.org)
Filed under fragile x syndrome toxic protein nerve cells gene mutation DNA sequence neuroscience science
TAU reveals the missing link between brain patterns and Alzheimer’s
Evidence indicates that the accumulation of amyloid-beta proteins, which form the plaques found in the brains of Alzheimer’s patients, is critical for the development of Alzheimer’s disease, which impacts 5.4 million Americans. And not just the quantity, but also the quality of amyloid-beta peptides is crucial for Alzheimer’s initiation. The disease is triggered by an imbalance in two different amyloid species — in Alzheimer’s patients, there is a reduction in a relative level of healthy amyloid-beta 40 compared to 42.
Now Dr. Inna Slutsky of Tel Aviv University’s Sackler Faculty of Medicine and the Sagol School of Neuroscience, with postdoctoral fellow Dr. Iftach Dolev and PhD student Hilla Fogel, have uncovered two main features of the brain circuits that impact this crucial balance. The researchers have found that patterns of electrical pulses (called “spikes”) in the form of high-frequency bursts and the filtering properties of synapses are crucial to the regulation of the amyloid-beta 40/42 ratio. Synapses that transfer information in spike bursts improve the amyloid-beta 40/42 ratio.
This represents a major advance in understanding that brain circuits regulate composition of amyloid-beta proteins, showing that the disease is not just driven by genetic mutations, but by physiological mechanisms as well. Their findings were recently reported in the journal Nature Neuroscience.
Tipping the balance
High-frequency bursts in the brain are critical for brain plasticity, information processing, and memory encoding. To check the connection between spike patterns and the regulation of amyloid-beta 40/42 ratio, Dr. Dolev applied electrical pulses to the hippocampus, a brain region involved in learning and memory.
When increasing the rate of single pulses at low frequencies in rat hippocampal slices, levels of both amyloid-beta 42 and 40 grew, but the 40/42 ratio remained the same. However, when the same number of pulses was distributed in high-frequency bursts, researchers discovered an increased amyloid-beta 40 production. In addition, the researchers found that only synapses optimized to transfer encoded by bursts contributed towards tipping the balance in favor of amyloid-beta 40. Further investigations conducted by Fogel revealed that the connection between spiking patterns and the type of amyloid-beta produced could revolve around a protein called presenilin. “We hypothesize that changes in the temporal patterns of spikes in the hippocampus may trigger structural changes in the presenilin, leading to early memory impairments in people with sporadic Alzheimer’s,” explains Dr. Slutsky.
Behind the bursts
According to Dr. Slutsky, different kinds of environmental changes and experiences — including sensory and emotional experience — can modify the properties of synapses and change the spiking patterns in the brain. Previous research has suggested that a stimulant-rich environment could be a contributing factor in preventing the development of Alzheimer’s disease, much as crossword and similar puzzles appear to stimulate the brain and delay the onset of Alzheimer’s. In the recent study, the researchers discovered that changes in sensory experiences also regulate synaptic properties — leading to an increase in amyloid-beta 40.
In the next stage, Dr. Slutsky and her team are aiming to manipulate activity patterns in the specific hippocampal pathways of Alzheimer’s models to test if it can prevent the initiation of cognitive impairment. The ability to monitor dynamics of synaptic activity in humans would be a step forward early diagnosis of sporadic Alzheimer’s.
(Source: aftau.org)
Filed under brain brain circuits amyloid beta proteins alzheimer's disease plasticity neurons neuroscience science
Hologram-like 3-D brain helps researchers decode migraine pain
Wielding a joystick and wearing special glasses, pain researcher Alexandre DaSilva rotates and slices apart a large, colorful, 3-D brain floating in space before him.
Despite the white lab coat, it appears DaSilva’s playing the world’s most advanced virtual video game. The University of Michigan dentistry professor is actually hoping to better understand how our brains make their own pain-killing chemicals during a migraine attack.
The 3-D brain is a novel way to examine data from images taken during a patient’s actual migraine attack, says DaSilva, who heads the Headache and Orofacial Pain Effort at the U-M School of Dentistry and the Molecular and Behavioral Neuroscience Institute.
Different colors in the 3-D brain give clues about chemical processes happening during a patient’s migraine attack using a PET scan, or positron emission tomography, a type of medical imaging.
"This high level of immersion (in 3-D) effectively places our investigators inside the actual patient’s brain image," DaSilva said.
The 3-D research occurs in the U-M 3-D Lab, part of the U-M Library.
Filed under virtual reality migraine 3-D brain brain positron emission tomography pain neuroscience science
First steps of synapse building captured in live zebra fish embryos
Using spinning disk microscopy on barely day-old zebra fish embryos, University of Oregon scientists have gained a new window on how synapse-building components move to worksites in the central nervous system.
What researchers captured in these see-through embryos — in what may be one of the first views of early glutamate-driven synapse formation in a living vertebrate — were orderly movements of protein-carrying packets along axons to a specific site where a synapse would be formed.
Washbourne addresses:
► The basic importance of the findings
► The connection to diseases, including autism
The discovery, in research funded by the National Institutes of Health, is described in a paper placed online ahead of publication in the April 25 issue of the open-access journal Cell Reports. It is noteworthy because most synapses formed in vertebrates use glutamate as a neurotransmitter, and breakdowns in the process have been tied to conditions such as autism, schizophrenia and mental retardation.
The zebra fish has become one of the leading research models for studying early development, in general, and human-disease states.
In this case, researchers used immunofluorescence labeling to highlight the area they put under the microscopes. The embryos they studied were barely 24-hours old and a millimeter in length, but neurons in their spinal cord were already forming connections called synapses. Images were taken every 30 seconds over two hours.
"If we zoom out a bit and look at development in the human, the majority of synapse formation occurs in the cortex after birth and continues for the first two years in a baby’s life," said Philip Washbourne, a professor of biology and member of the UO’s Institute of Neuroscience.
Previous studies, done in vitro, contradicted each other, with one, in 2000, identifying a single packet of building blocks arriving at a pre-synaptic terminal. The other, in 2004, identified two protein packets. After watching the process unfold live, with imaging over long time spans, Washbourne said: “We now see at least three, and maybe more, such deliveries.”
"Axons are long processes — think of them as highways — of neurons. In humans, these can be a meter long, from spinal cord to your big toe," he said. It’s in the cell body where all the proteins are made, and they have to be transported out. Is it done by a single bus or by several cars? These results point to additional layers of complexity in the established mechanisms of synaptogenesis."
The new research also showed that sequence also is crucial. Two different pre-synaptic packages of molecules repeatedly arrived in the same order. A key building block — the protein synapsin — always arrived third. As these delivery vehicles traveled the axonal highway, another protein, a cyclin-dependent kinase known as Cdk5, acts as a stoplight at the synapse-construction site, where phosphorylation occurs. More research is needed on Cdk5, Washbourne said.
"Understanding how all this happens will inform us to what’s going wrong in neurodevelopment that leads to diseases," Washbourne said. "We have indications that the glue that gets all this going includes a gene that has been linked to autism, so knowing how these molecules start the process of synapse formation — and what goes wrong in people with mutations in these genes — might allow for a therapeutic targeting to correct the mutations and manipulate the stop signs."
Filed under zebrafish CNS glutamate synapses neurotransmitters autism schizophrenia mental retardation neuroscience science
Neural Activity in Bats Measured In Flight
Animals navigate and orient themselves to survive – to find food and shelter or avoid predators, for example. Research conducted by Dr. Nachum Ulanovsky and research student Michael Yartsev of the Weizmann Institute’s Neurobiology Department, published today in Science, reveals for the first time how three-dimensional, volumetric, space is perceived in mammalian brains. The research was conducted using a unique, miniaturized neural-telemetry system developed especially for this task, which enabled the measurement of single brain cells during flight.
The question of how animals orient themselves in space has been extensively studied, but until now experiments were only conducted in two-dimensional settings. These have found, for instance, that orientation relies on “place cells” – neurons located in the hippocampus, a part of the brain involved in memory, especially spatial memory. Each place cell is responsible for a spatial area, and it sends an electrical signal when the animal is located in that area. Together, the place cells produce full representations of whole spatial environments. Unlike the laboratory experiments, however, the navigation of many animals in the real world, including humans, is carried out in three dimensions. But attempts to expand the scope of experiments from two to three dimensions had encountered difficulties.
One of the more famous efforts in this area was conducted by the University of Arizona and NASA, in which they launched rats into space (aboard a space shuttle). However, although the rats moved around in zero gravity, they ran along a set of straight, one-dimensional lines. Other experiments with three-dimensional projections onto two-dimensional surfaces did not manage to produce volumetric data, either. The conclusion was that in order to understand movement in three-dimensional, volumetric space, it is necessary to allow animals to move through all three dimensions – that is, to research animals in flight.
Ulanovsky chose to study the Egyptian fruit bat, a very common bat species in Israel. Because these are relatively large, the researchers were able to attach the wireless measuring system in a manner that did not restrict the bats’ movements. Developing this sophisticated measuring system was a several-year effort. Ulanovsky, in cooperation with a US commercial company, created a wireless, lightweight (12 g, about 7% of the weight of the bat) device containing electrodes that measure the activity of individual neurons in the bat’s brain.
The next challenge the scientists faced was adapting the behavior of their bats to the needs of the experiment. Bats naturally fly toward their destination – for example, a fruit tree – in a straight line. In other words, their normal flight patterns are one-dimensional, while the experiment required their flights to fill a three-dimensional space.
The solution was to be found in a previous study in Ulanovsky’s group, which tracked wild fruit bats using miniature GPS devices. One of the discoveries was that when bats arrive at a fruit tree, they fly around it, utilizing the full volume of space surrounding the tree. To simulate this behavior in the laboratory – an artificial cave equipped with an array of bat-monitoring devices – the team installed an artificial “tree” made of metal bars and cups filled with fruit.
Measuring the activity of hippocampus neurons in the bats’ brains revealed that the representation of three-dimensional space is similar to that in two dimensions: Each place cell is responsible for identifying a particular spatial area in the “cave” and sends an electrical signal when the bat is located in that area. Together, the population of place cells provides full coverage of the cave – left and right, up and down.
A closer examination of the areas for which individual place cells are responsible provided an answer to a highly-debated question: Does the brain perceive the three dimensions of space as “equal,” that is, does it sense the height axis in the same way as that of length or width? The findings suggest that each place cell responds to a spherical volume of space, i.e., the perception of all three dimensions is uniform. The researchers note that for those non-flying animals that essentially move in flat space, the different axes might not be perceived at the same resolution. It may be that such animals are naturally more sensitive to changes along the length and width axes than that of height. This question is of particular interest when it comes to humans because on the one hand, humans evolved from apes that moved in three-dimensional space when swinging from branch to branch, but on the other hand, modern, ground-dwelling humans generally navigate in two-dimensional space.
The findings provide new insights into some basic functions of the brain: navigation, spatial memory and spatial perception. To a large extent, this is due to the development of innovative technology that allowed the first glimpse into the brain of a flying animal. Ulanovsky believes that this trend, in which research is becoming more “natural,” is the future wave of neuroscience.
Filed under bats brain cells neurons hippocampus spatial memory navigation three-dimensional space flying neuroscience science
Bat and Rat Brain Rhythms Differ When on the Move
To get a clear picture of how humans and other mammals form memories and find their way through their surroundings, neuroscientists must pay more attention to a broad range of animals rather than focus on a single model species, say two University of Maryland researchers, Katrina MacLeod and Cynthia Moss. Their new comparative study of bats and rats reports differences between the species that suggest the need to revise models of spatial navigation.
In a paper appearing in the April 19, 2013 issue of Science, the UMD researchers and two colleagues at Boston University reported significant differences between rats’ and bats’ brain rhythms when certain cells were active in a part of the brain used in memory and navigation.
These cells behaved as expected in rats, which mostly move along surfaces. But in bats, which fly, the continuous brain rhythm did not appear, said Moss, a professor in Psychology and Biology and the Institute for Systems Research.
The finding suggests that even though rats, bats, humans and other mammals share a common neural representation of space in a part of the brain that has been linked to spatial information and memory, they may have different cellular mechanisms to create or interpret those maps, said MacLeod, an assistant research scientist in Biology.
“To understand brains, including ours, we really must study neural activity in a variety of animals,” MacLeod said. “Common features across multiple species tell us ‘Aha, this is important,’ but differences can occur because of variances in the animals’ ecology, behavior, or evolutionary history.”
The research team focused on a brain region that contains specialized “grid cells,” so named because they form a hexagonal grid of activity related to the animal’s location as it navigates through space. This brain region, the medial entorhinal cortex, sits next to the hippocampus, the place that, in humans, forms memories of events such as where a car is parked. The medial entorhinal cortex acts as a hub of neural networks for memory and navigation.
Grid cells were first noticed in rats navigating their environment, but recent work by Nachum Ulanovsky (Moss’s former postdoctoral researcher at UMD) and his research team at the Weizmann Institute in Rehovot, Israel, has shown these cells exist in bats as well.
In rats, grid cells fire in a pattern called a theta wave when the animals spatially navigate. Theta waves are fairly low-frequency electrical oscillations that also have been observed at the cellular level in the medial entorhinal cortex. The prominence of theta waves in rats suggested they were important. As a result, neuroscientists, trying to understand the relationship between theta waves and grid cells, have developed models of the brain based on the assumption that theta waves are key to spatial navigation in mammals.
However, Moss said, “recordings from the brains of bats navigating in space contain a surprise, because the expected theta rhythms aren’t continuously present as they are in the rodent.”
The new Science study doubles down on the lack of theta in bats by reporting that theta rhythms also are not present at the cellular level. “The bat neurons don’t ‘ring’ the way the rat neurons do,” says MacLeod. “This raises a lots of questions as to whether theta rhythms are actually doing what the spatial navigation theory proposes in rats or even humans.”
Filed under brain cells spatial navigation neural activity brain tissue bats rats brain rhythms neuroscience science
Information from the senses has an important influence on how we move. For instance, you can see and feel when a mug is filled with hot coffee, and you lift it in a different way than if the mug were empty. Neuroscientist Julian Tramper discovered that the brain uses two forms of old information in order to execute new movements well. This discovery can be useful for the field of robotics. Tramper will receive his doctorate on Thursday 24 April from Radboud University Nijmegen
Every time you move, the brain deals with two problems. First, there is a slight delay in the sensory information needed to execute the movement. Second, the command from the brain directing the muscles to move is not entirely clear, because neuronal signals contain a certain amount of natural static interference. According to Tramper, the brain has a clever way of getting around both problems: It combines the old information from the senses with experience gained through similar movements made in the past. This means that our senses use two forms of old information in order to make new movements.
Computer versus test subject
Understanding the brain processes behind movement can be of great importance to fields like robotics. Therefore Tramper is trying to model his findings so that it will be possible to use them in robots in the future. He has already succeeded in this for certain hand-eye coordination experiments, to the extent that a computer can perform at about the same level as human test subjects. As a post-doctoral researcher within the Donders Institute, Tramper is researching how these types of models can be integrated into bio-inspired robots (robots based on biological principles).
SpaceCog
Tramper is currently working on a project called SpaceCog. The goal of this project is to develop a robot which can independently orient itself in space, something that humans do automatically. This is difficult to achieve, because each time a robot moves, it must reinterpret the information from its cameras and other sensors in order to determine whether the changes to its input are the result of its own movement or an external cause. The researchers involved in SpaceCog want to figure out how our brain has solved this problem. Tramper has three years to come up with a good computer model addressing this issue.
Looking towards the future
Tramper is studying hand-eye coordination by having test subjects play a special computer game. The subjects use a game controller to move a digital right hand and left hand on a screen. They have to move the two hands independently of one another and make them each follow a particular path in order to reach a final destination (see film 1). It turned out that the test subject’s eyes moved ahead of the digital hands. In other words, the eyes looked at a point that the hands would reach in the future (see film 2). This type of eye movement is called smooth pursuit, and before now it had only been detected in the case of external stimuli, when a subject was following an object’s movement. Tramper detected smooth pursuit eye movements at locations the hands had not yet reached, meaning these movements were triggered by internal stimuli.
Smooth pursuit
Tramper explains, ‘We’d previously demonstrated for other types of eye movement that the eye anticipates and moves in advance of external movement To our surprise, this is also the case with smooth pursuit. It is probable that this is a compromise between where you are at a particular moment and where you want to get to. When moving, you need to keep track of your current location (which is constantly changing) and your target destination. Smooth pursuit eye movements can help you do this by letting your eye “hover” between both locations. If we can teach robots to do something like this, it will help make their movements much more natural. This will increase the number of ways in which robots can be put to work.’
(Source: ru.nl)
Filed under sensory information robots robotics motor movements hand-eye coordination SpaceCog neuroscience science
Exosomes are small, virus-like particles that can transport genetic material and signal substances between cells. Researchers at Lund University, Sweden, have made new findings about exosomes released from aggressive brain tumours, gliomas. These exosomes are shown to have an important function in brain tumour development, and could be utilised as biomarkers to assess tumour aggressiveness through a blood test.
“Current wisdom says that cells are closed entities that communicate through the secretion of soluble signalling molecules. Recent findings indicate that cells can exchange more complex information – whole packages of genetic material and signalling proteins. This is an entirely new conception of how cells communicate”, says Dr Mattias Belting, Professor of Oncology at Lund University and senior consultant in oncology at Skåne University Hospital, Lund, Sweden.
Exosomes are small vesicles of only 30–90 nm. They are produced inside cells and act as “transport vehicles” of genetic material that can be transferred to surrounding cells. Since their first discovery, exosomes have been found in blood, saliva, urine, breast milk and other body fluids.
Mattias Belting’s research group has investigated exosomes released from tumour cells of patients with gliomas. The tiny exosome particles are delivered from the tumour to healthy cells of the brain and may prime normal tissue for efficient spreading of the tumour. The researchers in Lund have now shown that the aggressiveness of the tumour is reflected in the exosome molecular profile.
“We have succeeded in developing a method for the isolation of exosomes from brain tumour patients through a relatively simple blood test. Our analyses indicate that the content of exosomes mirrors the aggressiveness of the tumour in a unique manner”, says postdoctoral researcher Paulina Kucharzewska.
Exosomes could thus be utilised as biomarkers, i.e. to provide guidance on how the patient should be treated and to monitor treatment response. This possibility is particularly attractive with brain tumours that are not readily accessible for tissue biopsy. However, analysis of exosomes from the blood may also prove important with other tumour types. The value of conventional tumour biopsies is limited by the heterogeneity of tumour tissue, i.e. the tissue specimen may not be fully representative of the biological characteristics of a particular tumour. Exosomes, however, may offer more comprehensive information, according to the researchers.
The second international meeting on exosomes has just opened in Boston, and Mattias Belting and members of his team are there.
“It is very exciting to be part of the emergence of a novel research field. It can be anticipated that the most influential researchers in this area may one day be awarded the Nobel Prize”, says Dr Belting.
The results are published in Proceedings of the National Academy of Sciences (PNAS).
(Source: lunduniversity.lu.se)
Filed under glioma brain tumours exosomes brain cells biomarkers neuroscience science
Scientists probe the source of a pulsing signal in the sleeping brain
New findings clarify where and how the brain’s “slow waves” originate. These rhythmic signal pulses, which sweep through the brain during deep sleep at the rate of about one cycle per second, are assumed to play a role in processes such as consolidation of memory. For the first time, researchers have shown conclusively that slow waves start in the cerebral cortex, the part of the brain responsible for cognitive functions. They also found that such a wave can be set in motion by a tiny cluster of neurons.
"The brain is a rhythm machine, producing all kinds of rhythms all the time," says Prof. Arthur Konnerth of the Technische Universitaet Muenchen (TUM). "These are clocks that help to keep many parts of the brain on the same page." One such timekeeper produces the so-called slow waves of deep sleep, which are thought to be involved in transmuting fragments of a day’s experience and learning into lasting memory. They can be observed in very early stages of development, and they may be disrupted in diseases such as Alzheimer’s.
Previous studies, relying mainly on electrical measurements, have lacked the spatial resolution to map the initiation and propagation of slow waves precisely. But using light, Konnerth’s Munich-based team – in collaboration with researchers at Stanford and the University of Mainz – could both stimulate slow waves and observe them in unprecedented detail. One key result confirmed that the slow waves originate only in the cortex, ruling out other long-standing hypotheses. “The second major finding,” Konnerth says, “was that out of the billions of cells in the brain, it takes not more than a local cluster of fifty to one hundred neurons in a deep layer of the cortex, called layer 5, to make a wave that extends over the entire brain.”
New light on a fundamental neural mechanism
Despite considerable investigation of the brain’s slow waves, definitive answers about the underlying circuit mechanism have remained elusive. Where is the pacemaker for this rhythm? Where do the waves start, and where do they stop? This study – based on optical probing of intact brains of live mice under anesthesia – now provides the basis for a detailed, comprehensive view.
"We implemented an optogenetic approach combined with optical detection of neuronal activity to explore causal features of these slow oscillations, or Up-Down state transitions, that represent the dominating network rhythm in sleep," explains Prof. Albrecht Stroh of the Johannes Gutenberg University Mainz. Optogenetics is a novel technique that enabled the researchers to insert light-sensitive channels into specific kinds of neurons, to make them responsive to light stimulation. This allowed for selective and spatially defined stimulation of small numbers of cortical and thalamic neurons.
Access to the brain via optical fibers allowed for both microscopic recording and direct stimulation of neurons. Flashes of light near the mouse’s eyes were also used to stimulate neurons in the visual cortex. By recording the flux of calcium ions, a chemical signal that can serve as a more spatially precise readout of the electric activity, the researchers made the slow waves visible. They also correlated optical recordings with more conventional electrical measurements. As a result, it was possible to watch individual wave fronts spread – like ripples from a rock thrown into a quiet lake – first through the cortex and then through other brain structures.
A new picture begins to emerge: Not only is it possible for a tiny local cluster of neurons to initiate a slow wave that will spread far and wide, recruiting multiple regions of the brain into a single event – this appears to be typical. “In spontaneous conditions,” Konnerth says, “as it happens with you and me and everyone else every night in deep sleep, every part of the cortex can be an initiation site.” Furthermore, a surprisingly simple communication protocol can be seen in the slow wave rhythm. During each one-second cycle a single neuron cluster sends its signal and all others are silenced, as if they are taking turns bathing the brain in fragments of experience or learning, building blocks of memory. The researchers view these findings as a step toward a better understanding of learning and memory formation, a topic Konnerth’s group is investigating with funding from the European Research Council. They also are testing how the slow waves behave during disease.
Filed under sleep deep sleep brainwaves cerebral cortex optogenetics neurons neuroscience science
Researchers at the University Department of Neurology at the MedUni Vienna have identified a gene behind an epilepsy syndrome, which could also play an important role in other idiopathic (genetically caused) epilepsies. With the so-called “next generation sequencing”, with which genetic changes can be identified within a few days, it was ascertained that the CNTN2 gene is defective in this type of epilepsy.
This was investigated by a team led by Elisabeth Stögmann in collaboration with Cairo’s Ain Shams University and the Helmholtz Centre Munich with reference to a particular Egyptian family, in which five sick children have resulted from the marriage of one healthy cousin to his, likewise healthy, second cousin. The children affected suffer from a specific epilepsy syndrome, in which different types of epileptic attacks occur. This constellation has the “advantage”, according to Stögmann, that both alleles of the gene, which is how one designates different forms of the gene, demonstrate this defect: “As a result the defect becomes symptomatic and identifiable.
"20,000 to 25,000 genes, including all the "protein coding" ones, were sequenced for this. When this was done a mutation was found in the CNTN2 gene. CNTN2 undertakes an important function in the anchoring of potassium channels to the synapses. The mutation makes it no longer possible to generate this protein and, as a consequence, the potassium channels no longer remain affixed to the synapses. The researchers suspect that the epilepsy in this family is triggered by the altered function of the potassium channels.
This discovery, which has now been published in the top journal “Brain”, is providing the stimulus for further research to investigate this particular gene in other epilepsy patients as well. Approximately one percent of the population suffers from active epilepsy in which regular epileptic fits occur. The danger of suffering from an epileptic fit once in your life lies at approximately four to five percent. Genetic factors play a major part in the occurrence of epilepsies.
(Source: meduniwien.ac.at)
Filed under epilepsy genes mutations synapses potassium channels neuroscience science
