Posts tagged neuron
Articles and news from the latest research reports.
Researchers have taken a key step towards recovering specific brain functions in sufferers of brain disease and injuries by successfully restoring the decision-making processes in monkeys.
By placing a neural device onto the front part of the monkeys’ brains, the researchers, from Wake Forest Baptist Medical Centre, University of Kentucky and University of Southern California, were able to recover, and even improve, the monkeys’ ability to make decisions when their normal cognitive functioning was disrupted.
The study, which has been published today (Sept. 14) in IOP Publishing’s Journal of Neural Engineering, involved the use of a neural prosthesis, which consisted of an array of electrodes measuring the signals from neurons in the brain to calculate how the monkeys’ ability to perform a memory task could be restored.
![Stem Cells Turn Hearing Back On
Scientists have enabled deaf gerbils to hear again—with the help of transplanted cells that develop into nerves that can transmit auditory information from the ears to the brain. The advance, reported in Nature, could be the basis for a therapy to treat various kinds of hearing loss.
In humans, deafness is most often caused by damage to inner ear hair cells—so named because they sport hairlike cilia that bend when they encounter vibrations from sound waves—or by damage to the neurons that transmit that information to the brain. When the hair cells are damaged, those associated spiral ganglion neurons often begin to degenerate from lack of use. Implants can work in place of the hair cells, but if the sensory neurons are damaged, hearing is still limited.
"Obviously the ultimate aim is to replace both cell types," says Marcelo Rivolta of the University of Sheffield in the United Kingdom, who led the new work. "But we already have cochlear implants to replace hair cells, so we decided the first priority was to start by targeting the neurons."
In the past, scientists have tried to isolate so-called auditory stem cells from embryoid bodie—aggregates of stem cells that have begun to differentiate into different types. But such stem cells can only divide about 25 times, making it impossible to produce them in the quantity needed for a neuron transplant.
Rivolta and his colleagues knew that during embryonic development, a handful of proteins, including fibroblast growth factor (FGF) 3 and 10, are required for ears to form. So they exposed human embryonic stem cells to FGF3 and FGF10. Multiple types of cells formed, including precursor inner-ear hair cells, but they were also able to identify and isolate the cells beginning to differentiate into the desired spiral ganglion neurons. Then, they implanted the neuron precursor cells into the ears of gerbils with damaged ear neurons and followed the animals for 10 weeks. The function of the neurons was restored.
"We’ve only followed the animals for a very limited time," Rivolta says. "We want to follow them long-term now"—both to assess the possibility of increased cancer risk and to observe the long-term function of the new neurons, he adds.
"It’s very exciting," says neuroscientist Mark Maconochie of Sussex University in the United Kingdom, who was not involved in the new work. "In the past, there has been work where someone makes a single hair cell or something that looks like one neuron [from stem cells], and even that gets the field excited. This is a real step change."
The question now, he says, is whether the procedure can be fine-tuned to allow more efficient production of the relay neurons—currently, fewer than 20% of the stem cells treated develop into those ear neurons. By combining growth factors other than FGF3 and FGF10 with the stem cell mix, researchers could harvest even more ear progenitor cells, he hypothesizes.
"The next big challenge will be to do something as effective as this for the hair cells," Maconochie adds.](http://41.media.tumblr.com/tumblr_ma9zpdq0n31rog5d1o1_500.jpg)
Stem Cells Turn Hearing Back On
Scientists have enabled deaf gerbils to hear again—with the help of transplanted cells that develop into nerves that can transmit auditory information from the ears to the brain. The advance, reported in Nature, could be the basis for a therapy to treat various kinds of hearing loss.
In humans, deafness is most often caused by damage to inner ear hair cells—so named because they sport hairlike cilia that bend when they encounter vibrations from sound waves—or by damage to the neurons that transmit that information to the brain. When the hair cells are damaged, those associated spiral ganglion neurons often begin to degenerate from lack of use. Implants can work in place of the hair cells, but if the sensory neurons are damaged, hearing is still limited.
"Obviously the ultimate aim is to replace both cell types," says Marcelo Rivolta of the University of Sheffield in the United Kingdom, who led the new work. "But we already have cochlear implants to replace hair cells, so we decided the first priority was to start by targeting the neurons."
In the past, scientists have tried to isolate so-called auditory stem cells from embryoid bodie—aggregates of stem cells that have begun to differentiate into different types. But such stem cells can only divide about 25 times, making it impossible to produce them in the quantity needed for a neuron transplant.
Rivolta and his colleagues knew that during embryonic development, a handful of proteins, including fibroblast growth factor (FGF) 3 and 10, are required for ears to form. So they exposed human embryonic stem cells to FGF3 and FGF10. Multiple types of cells formed, including precursor inner-ear hair cells, but they were also able to identify and isolate the cells beginning to differentiate into the desired spiral ganglion neurons. Then, they implanted the neuron precursor cells into the ears of gerbils with damaged ear neurons and followed the animals for 10 weeks. The function of the neurons was restored.
"We’ve only followed the animals for a very limited time," Rivolta says. "We want to follow them long-term now"—both to assess the possibility of increased cancer risk and to observe the long-term function of the new neurons, he adds.
"It’s very exciting," says neuroscientist Mark Maconochie of Sussex University in the United Kingdom, who was not involved in the new work. "In the past, there has been work where someone makes a single hair cell or something that looks like one neuron [from stem cells], and even that gets the field excited. This is a real step change."
The question now, he says, is whether the procedure can be fine-tuned to allow more efficient production of the relay neurons—currently, fewer than 20% of the stem cells treated develop into those ear neurons. By combining growth factors other than FGF3 and FGF10 with the stem cell mix, researchers could harvest even more ear progenitor cells, he hypothesizes.
"The next big challenge will be to do something as effective as this for the hair cells," Maconochie adds.
Scientists discover how the brain ages
Researchers at Newcastle University have revealed the mechanism by which neurons, the nerve cells in the brain and other parts of the body, age.
The research, published in Aging Cell, opens up new avenues of understanding for conditions where the ageing of neurons are known to be responsible, such as dementia and Parkinson’s disease.
The ageing process has its roots deep within the cells and molecules that make up our bodies. Experts have previously identified the molecular pathway that react to cell damage and stems the cell’s ability to divide, known as cell senescence.
However, in cells that do not have this ability to divide, such as neurons in the brain and elsewhere, little was understood of the ageing process. Now a team of scientists at Newcastle University, led by Professor Thomas von Zglinicki have shown that these cells follow the same pathway.
This challenges previous assumptions on cell senescence and opens new areas to explore in terms of treatments for conditions such as dementia, motor neuron disease or age-related hearing loss.
Newcastle University’s Professor Thomas von Zglinicki who led the research said: “We want to continue our work looking at the pathways in human brains as this study provides us with a new concept as to how damage can spread from the first affected area to the whole brain.”
Working with the University’s special colony of aged mice, the scientists have discovered that ageing in neurons follows exactly the same rules as in senescing fibroblasts, the cells which divide in the skin to repair wounds.
DNA damage responses essentially re-program senescent fibroblasts to produce and secrete a host of dangerous substances including oxygen free radicals or reactive oxygen species (ROS) and pro-inflammatory signalling molecules. This makes senescent cells the ‘rotten apple in a basket’ that can damage and spoil the intact cells in their neighbourhood. However, so far it was always thought that ageing in cells that can’t divide - post-mitotic, non-proliferating cells - like neurons would follow a completely different pathway.
Now, this research explains that in fact ageing in neurons follows exactly the same rules as in senescing fibroblasts.
Professor von Zglinicki, professor of Cellular Gerontology at Newcastle University said: “We will now need to find out whether the same mechanisms we detected in mouse brains are also associated with brain ageing and cognitive loss in humans. We might have opened up a short-cut towards understanding brain ageing, should that be the case.”
Dr Diana Jurk, who did most of this work during her PhD in the von Zglinicki group, said: “It was absolutely fascinating to see how ageing processes that we always thought of as completely separate turned out to be identical. Suddenly so much disparate knowledge came together and made sense.”
(Source: ncl.ac.uk)
![Scientists have found that one gene is responsible for variability in locomotion in horses and mice.
Traits such as height are controlled by the interaction of up to 700 genes. So it came as quite a shock to researchers from Uppsala University (UU) and their international collaborators that the mutation of just a single gene is responsible for variability in locomotion in horses and mice. Furthermore, the research team discovered that this gene, DMRT3, is expressed in a previously unknown set of neurons in the spinal cord. These findings provide insight into the neural circuits that coordinate movement in vertebrates.
“The amazing result was that we found one very strong signal on one chromosome which by further work led to the discovery of the DMRT3 mutation,” explains Leif Andersson, co-author of the paper published in Nature, from UU and Swedish University of Agricultural Sciences. “This was unexpected since we had [anticipated] a much more complex genetic background for a trait like this.”](http://33.media.tumblr.com/tumblr_ma13qp01ib1rog5d1o1_500.gif)
Scientists have found that one gene is responsible for variability in locomotion in horses and mice.
Traits such as height are controlled by the interaction of up to 700 genes. So it came as quite a shock to researchers from Uppsala University (UU) and their international collaborators that the mutation of just a single gene is responsible for variability in locomotion in horses and mice. Furthermore, the research team discovered that this gene, DMRT3, is expressed in a previously unknown set of neurons in the spinal cord. These findings provide insight into the neural circuits that coordinate movement in vertebrates.
“The amazing result was that we found one very strong signal on one chromosome which by further work led to the discovery of the DMRT3 mutation,” explains Leif Andersson, co-author of the paper published in Nature, from UU and Swedish University of Agricultural Sciences. “This was unexpected since we had [anticipated] a much more complex genetic background for a trait like this.”
Master gene affects neurons that govern breathing at birth and adulthood
When mice are born lacking the master gene Atoh1, none breathe well and all die in the newborn period. Why and how this occurs could provide new answers about sudden infant death syndrome (SIDS), but the solution has remained elusive until now.
Research led by Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital demonstrates that when the gene is lacking in a special population of neurons called RTN (retrotrapezoid nucleus), roughly half the young mice die at birth. Those who survive are less likely to respond to excess levels of carbon dioxide as adults. A report of their work appears online in the journal Neuron.
"The death of mice at birth clued us in that Atoh1 must be needed for the function of some neurons critical for neonatal breathing, so we set out to define these neurons," said Dr. Huda Zoghbi, senior author of the report and director of the Neurological Research Institute and a professor of molecular and human genetics, neuroscience, neurology and pediatrics at BCM. Zoghbi is also a Howard Hughes Medical Institute investigator.
"We took a genetic approach to find the critical neurons," said Wei-Hsiang Huang, a graduate student in the Program in Developmental Biology at BCM who works in Zoghbi’s laboratory. With careful studies to "knockout" the activity of the gene in a narrower and narrower area in the brain, they slowly eliminated possible neurons to determine that loss of Atoh1 in the RTN neurons was the source of the problem.
"Discovering that Atoh1 is indeed critical for the RTN neurons to take their right place in the brainstem and connect with the breathing center helped us uncover why they are important for neonatal breathing," said Zoghbi.
"This population of neurons resides in the ventral brainstem," said Huang. "When there is a change in the makeup of the blood (lack of oxygen or buildup of carbon dioxide), the RTN neurons sense that and tell the body to change the way it breathes." A defect in these neurons can disrupt this response.
"Without Atoh1 the mice have significant breathing problems because they do not automatically adjust their breathing to decrease carbon dioxide and oxygenate the blood," he said.
It turns out the findings from this mouse study are relevant to human studies.
"A paper just published reports that developmental abnormalities in the RTN neurons of children with sudden infant death syndrome or sudden unexplained intrauterine death may be linked to altered ventilatory response to carbon dioxide", said Huang (Lavezzi, A.M., et al., Developmental alterations of the respiratory human retrotrapezoid nucleus in sudden unexplained fetal and infant death, Auton. Neurosci. (2012), doi:10.1016/j.autneu.2012.06.005).
(Source: bcm.edu)
Every activity in the brain involves the transfer of signals between neurons. Frequently, as many as one thousand signals rain down on a single neuron simultaneously. To ensure that precise signals are delivered, the brain possesses a sophisticated inhibitory system. Stefan Remy and colleagues at the German Center for Neurodegenerative Diseases and the University Bonn have illuminated how this system works.
“The system acts like a filter, only letting the most important impulses pass,” explains Remy. “This produces the targeted neuronal patterns that are indispensible for long-term memory storage.”
A Blueprint for ‘Affective’ Aggression
A North Carolina State University researcher has created a roadmap to areas of the brain associated with affective aggression in mice. This roadmap may be the first step toward finding therapies for humans suffering from affective aggression disorders that lead to impulsive violent acts.
Affective aggression differs from defensive aggression or premeditated aggression used by predators, in that the role of affective aggression isn’t clear and could be considered maladaptive. NC State neurobiologist Dr. Troy Ghashghaei was interested in finding the areas of the brain engaged with this type of aggressive behavior. Using mice that had been specially bred for affective aggression by his research associate Dr. Derrick L Nehrenberg, Ghashghaei and former undergraduate student Atif Sheikh were able to locate the regions in the mouse brain that switched on and those that were off when the mice displayed affective aggression.
“The brain works by using clusters of neurons that cross communicate at extremely rapid rates, much like a computer,” Ghashghaei explains. “One region will process a stimulus, and then that region sends messages to other clusters within the brain, like circuits within a computer. We looked at how the switches flipped in the brains of aggressive mice, and compared that with the brains of completely nonaggressive mice in the same setting, to see how the two processed the situation differently.”
They found that affectively aggressive mice demonstrated a large difference in the way their “executive centers” operated when the mice encountered another mouse. “Sensory inputs come in and are sent to the executive center, the part of the brain that decides how to respond to the input,” Ghashghaei says. “In the meantime, the information about the response you made gets processed back with either a pleasant or unpleasant association.”
According to Ghashghaei, the affectively aggressive mice could react violently because their brains are hardwiredto respond to certain situations aggressively without assessing whether their response to the situation is appropriate or without regard to the behavior’s consequences. In addition, affectively aggressive mice may be forming pleasant associations with their violent displays, which would reinforce their aggressive tendencies.
“We cannot say which of the two possibilities underlie the persistent aggressive displays by our mice,” Ghashghaei says, “but we can see that the patterns of neuronal activity are very different in the executive centers of these mice. Additionally, there are differences in the neuronal clusters involved with creating pleasant or unpleasant associations to the stimulus or their response. That gives us a few starting spots to begin identifying the mechanisms that underlie these profound behavioral differences.”
The regions of the brain that were involved in affective aggression in the mice are similar across all mammalian species. Ghashghaei hopes that his findings in mice will be useful to researchers studying violent behavior in humans, as well as aggression in other animals.
“With the brain, just knowing where to start looking is huge,” Ghashghaei says. “Once you have a few targets, you can tease out the possibilities and get to the heart of the problem. We are confident that manipulation of some of the identified targets in our study will disrupt displays of affective aggression in our mouse model.”
(Source: news.ncsu.edu)
One biotech startup wants to restore vision in blind patients with a gene therapy that gives light sensitivity to neurons that don’t normally possess it.
The attempt, by Ann Arbor, Michigan-based Retrosense Therapeutics, will use so-called optogenetics. Scientists have used the technique over the last few years as a research tool to study brain circuits and the neural control of behavior by directing neuron activity with flashes of light. But Retrosense and others groups are pushing to bring the technique to patients in clinical trials.
The idea behind Retrosense’s experimental therapy is to use optogenetics to treat patients who have lost their vision due to retinal degenerative diseases such as retinitis pigmentosa. Patients with retinitis pigmentosa experience progressive and irreversible vision loss because the rods and cones of their eyes die due to an inherited condition. If the company is successful, the treatment could also help patients with the most common form of macular degeneration, which affects nearly a million people in the United States. The U.S. Food and Drug Administration hasn’t approved any therapies for either condition.
Robots hunt neurons to record brain activity
Devices could reveal inner workings of neurons and how they communicate with each other.
Automated assistance may soon be available to neuroscientists tackling the brain’s complex circuitry, according to research presented last week at the Aspen Brain Forum in Colorado. Robots that can find and simultaneously record the activity of dozens of neurons in live animals could help researchers to reveal how connected cells interpret signals from one another and transmit information across brain areas — a task that would be impossible using single-neuron studies.
A robot that can access the internal workings of neurons could be scaled up to allow 100 cells to be studied at a time. MIT McGovern Institute/E. Boyden/Sputnik Animation
The robots are designed to perform whole-cell patch-clamping, a difficult but powerful method that allows neuroscientists to access neurons’ internal electrical workings, says Edward Boyden of the Massachusetts Institute of Technology in Cambridge, who is leading the work.
Astrocytes Control the Generation of New Neurons from Neural Stem Cells
August 24th, 2012
Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny just published a research article in a prestigious journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain.
Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain’s response to neurotrauma or stroke.
Reduces brain tissue damage
Prof. Pekny’s laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.
Generation of new neurons
In their current study, the Sahlgrenska Academy researchers show how astrocytes control the generation of new neurons in the brain. An important contribution to this project came from Åbo Academy, one of Sahlgrenska’s traditional collaborative partners.
“In the brain, astrocytes control how many new neurons are formed from neural stem cells and survive to integrate into the existing neuronal networks. Astrocytes do this by secreting specific molecules but also by much less understood direct cell-cell interactions with stem cells”, says Prof. Milos Pekny.
Image shows GFAP stained cortex from a TgAPP mouse showing activated astrocytes from a different study.
Important regulator
“Astrocytes are in physical contact with neural stem cells and we have shown that they signal through the Notch pathway to stem cells to keep the birth rate of new neurons low. We have also shown that the intermediate filament system of astrocytes is an important regulator of this process. It seems that astrocyte intermediate filaments can be used as a target to increase the birthrate of new neurons.”
Target for future therapies
“We are starting to understand some of the cellular and molecular mechanisms behind the control of neurogenesis. Neurogenesis is one of the components of brain plasticity, which plays a role in the learning process as well as in the recovery after brain injury or stroke. This work helps us to understand how plasticity and regenerative response can be therapeutically promoted in the future”, says Prof. Milos Pekny.
Source: Neuroscience News