Posts tagged brain cells
Articles and news from the latest research reports.
New Study Points to a Brain Region Key to Contextual Memories
Dartmouth researchers demonstrate in a new study that a previously understudied part of the brain, the retrosplenial cortex, is essential for forming the basis for contextual memories, which help you to recall events ranging from global disasters to where you parked your car.
An important aspect of memory is the ability to recall the physical place, or context, in which an event occurred. For example, in recalling emotionally charged events such as the September 11 terror attacks or the assassination of President John F. Kennedy, we remember not only the event but also where we were when it happened. Indeed, in discussing such events with others, we often ask, “Where were you when … ?” Processing “where” information is also important for mundane events such as remembering where you parked your car.
Although it is known that a specific network of brain regions is important for contextual memory, it has not been known how different parts of the network contribute to this process. But using a newly developed technology known as “chemogenetics,” Professor David Bucci’s laboratory is beginning to show how different brain structures contribute to contextual learning and memory. Developed at the University of North Carolina School of Medicine, the chemogenetics technique enables researchers to “remotely control” the activity of brains cells. This is accomplished by using a virus to transfers genes for a synthetic receptor into a brain region. The receptors are responsive only to a synthetic drug that is administered through a simple injection. By binding to the receptors, the drug temporarily turns off—or on—brain cells in that region for a short amount of time.
Using this approach, Bucci’s laboratory demonstrated in an experiment with rats that the retrosplenial cortex is critical for forming the basis for contextual memories. It was the first time the chemogenetics technique had been used to turn off cells along the entire retrosplenial cortex. The importance of this finding is underscored by two recent studies showing that the hippocampus, another key brain region involved in contextual memories, is not itself active or necessary for forming the initial associations that underlie contextual memory.
The National Science Foundation recently awarded Bucci a five-year, $725,000 grant to continue this research.
“By providing new insight into the function of this part of the brain, our work will also have implications for understanding the basis for illnesses that impact contextual memory, such as Alzheimer’s disease,” Bucci says. “In fact, recent studies have shown that the retrosplenial cortex is one of the first brain areas that is damaged in persons with Alzheimer’s disease.”
The findings appear in The Journal of Neuroscience.
(Source: now.dartmouth.edu)
Scientists unravel mystery of brain cell growth
In the developing brain, special proteins that act like molecular tugboats push or pull on growing nerve cells, or neurons, helping them navigate to their assigned places amidst the brain’s wiring.
How a single protein can exert both a push and a pull force to nudge a neuron in the desired direction is a longstanding mystery that has now been solved by scientists from Dana-Farber Cancer Institute and collaborators in Europe and China.
Jia-huai Wang, PhD, who led the work at Dana-Farber and Peking University in Beijing, is a corresponding author of a report published in the August 7 online edition of Neuron that explains how one guidance protein, netrin-1, can either attract or repel a brain cell to steer it along its course. Wang and co-authors at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, used X-ray crystallography to reveal the three-dimensional atomic structure of netrin-1 as it bound to a docking molecule, called DCC, on the axon of a neuron. The axon is the long, thin extension of a neuron that connects to other neurons or to muscle cells.
As connections between neurons are established – in the developing brain and throughout life – axons grow out from a neuron and extend through the brain until they reach the neuron they are connecting to. To choose its path, a growing axon senses and reacts to different molecules it encounters along the way. One of these molecules, netrin-1, posed an interesting puzzle: an axon can be both attracted to and repelled from this cue. The axon’s behavior is determined by two types of receptors on its tip: DCC drives attraction, while UNC5 in combination with DCC drives repulsion.
“How netrin works at the molecular level has long been a puzzle in neuroscience field,” said Wang, “We now provide structure evidences that reveal a novel mechanism of this important guidance cue molecule.” The structure showed that netrin-1 binds not to one, but to two DCC molecules. And most surprisingly, it binds those two molecules in different ways.
“Normally a receptor and a signal are like lock-and-key, they have evolved to bind each other and are highly specific – and that’s what we see in one netrin site,” said Meijers. “But the second binding site is a very unusual one, which is not specific for DCC.”
Not all of the second binding site connects directly to a receptor. Instead, in a large portion of the binding interface, it requires small molecules that act as middle-men. These intermediary molecules seem to have a preference for UNC5, so if the axon has both UNC5 and DCC receptors, netrin-1 will bind to one copy of UNC5 via those molecules and the other copy of DCC at the DCC-specific site. This triggers a cascade of events inside the cell that ultimately drives the axon away from the source of netrin-1, author Yan Zhang’s lab at Peking University found. The researchers surmised that, if an axon has only DCC receptors, each netrin-1 molecule binds two DCC molecules, which results in the axon being attracted to netrin-1. “By controlling whether or not UNC5 is present on its tip, an axon can switch from moving toward netrin to moving away from it, weaving through the brain to establish the right connection,” said Zhang.
Knowing how neurons switch from being attracted to netrin to being repelled opens the door to devise ways of activating that switch in other cells that respond to netrin cues, too. For instance, many cancer cells produce netrin to attract growing blood vessels that bring them nourishment and allow the tumor to grow, so switching off that attraction could starve the tumor, or at least prevent it from growing.
On the other hand, when cancers metastasize they often stop being responsive to netrin. In fact, the DCC receptor was first identified as a marker for an aggressive form of colon cancer, and DCC stands for “deleted in colorectal cancer.” Since colorectal cancer cells have no DCC, they are ‘immune’ to the programmed cell death that would normally follow once they move away from the lining of the gut and no longer have access to netrin. As a result, these tumor cells continue to move into the bloodstream, and metastasize to other tissues. “Therefore, to understand the molecular mechanism of how netrin works should also have a good impact in cancer biology,” said Wang.
The guidance issue is a very complicated cell biology problem. Meijers, Zhang, Wang and their colleagues are now investigating how other receptors bind to netrin-1, exactly how the intermediary molecules ‘choose’ their preferred receptor, how other guidance molecule binds to DCC, and how the system is regulated. The answers could one day enable researchers to steer a cell’s response to netrin and other guidance cues, ultimately changing its fate.
Study Suggests Disruptive Effects of Anesthesia on Brain Cell Connections Are Temporary
A study of juvenile rat brain cells suggests that the effects of a commonly used anesthetic drug on the connections between brain cells are temporary.
The study, published in this week’s issue of the journal PLOS ONE, was conducted by biologists at the University of California, San Diego and Weill Cornell Medical College in New York in response to concerns, arising from multiple studies on humans over the past decade, that exposing children to general anesthetics may increase their susceptibility to long-term cognitive and behavioral deficits, such as learning disabilities.
An estimated six million children, including 1.5 million infants, undergo surgery in the United States requiring general anesthesia each year and a least two large-scale clinical studies are now underway to determine the potential risks to children and adults.
“Since these procedures are unavoidable in most cases, it’s important to understand the mechanisms associated with the potentially toxic effects of anesthetics on the developing brain, and on the adult brain as well,” said Shelley Halpain, a professor of biology at UC San Diego and the Sanford Consortium for Regenerative Medicine, who co-headed the investigation. “Because the clinical studies haven’t been completed, preclinical studies, such as ours, are needed to define the effects of various anesthetics on brain structure and function.”
“There is concern now about cognitive dysfunction from surgery and anesthesia—how much these effects are either permanent or slowly reversible is very controversial,” said Hugh Hemmings, Jr., chair of anesthesiology at Weill Cornell and the study’s other senior author. “It has been suggested recently that some of the effects of anesthesia may be more lasting than previously thought. It is not clear whether the residual effects after an operation are due to the surgery itself, or the hospitalization and attendant trauma, medications and stress—or a combination of these issues.”
However, he added, “There is evidence that some of the delayed or persistent cognitive effects after surgery are not primarily due to anesthesia itself, but more importantly to brain inflammation resulting from the surgery. But this is not yet clear.”
The team of biologists examined one of the most commonly used general anesthetics, a derivative of ether called “isoflurane” used to maintain anesthesia during surgery.
“Previous studies in cultured neurons and in the intact brains of rodents provided evidence suggesting that exposure to anesthetics might render neurons more susceptible to cell death through a process called ‘apoptosis’,” said Halpain. “While overt cell death could certainly be one way to explain any long-lasting neurocognitive consequences of general anesthesia, we hypothesized that there could be other cellular mechanisms that disrupt neural circuits without inducing cell death per se.”
One such mechanism, she added, is known as “synaptotoxicity.” In this mechanism of neural-circuit disruption, the “synapses,” or junctions between neurons, become weakened or shrink away due to some factor that injures the neurons locally along their axons (the long processes of neurons that transmit signals) and dendrites (the threadlike extensions of neurons that receive nerve signals) without inducing the neurons themselves to die.
In the experiments at UC San Diego headed by Jimcy Platholi, a postdoctoral researcher in Halpain’s lab who is now at Weill Cornell, the scientists used neurons from embryonic rats taken from the hippocampus, a part of the mammalian forebrain essential for encoding newly acquired memories and ensuring that short-term memories are converted into long-term memories. The researchers cultured these brain cells in a laboratory dish for three weeks, allowing the neurons time to mature and to develop a dense network of synaptic connections and “dendritic spines”—specialized structures that protrude from the dendrites and are essential mediators of activity throughout neural networks.
“Evidence from animal studies indicates that new dendritic spines emerge and existing spines expand in size during learning and memory,” explained Halpain. “Therefore, the overall numbers and size of dendritic spines can profoundly impact the strength of neural networks. Since neural network activity underlies all brain function, changes in dendritic spine number and shape can influence cognition and behavior.”
Using neurons in culture, rather than intact animal brains, allowed the biologists to take images of the synapses at high spatial resolution using techniques called fluorescence light microscopy and confocal imaging. They also used time-lapse microscopy to observe structural changes in individual dendritic spines during exposure to isoflurane. Karl Herold, a research associate in the Hemmings laboratory and a co-author of the study, performed some of the image analysis.
“Imaging of human brain synapses at this level of detail is impossible with today’s technology and it remains very challenging even in laboratory rodents,” said Halpain. “It was important that we performed our study using rodent neurons in a culture dish, so that we could really drill down into the subcellular and molecular details of how anesthetics work.”
The researchers wondered whether brief exposure to isoflurane would alter the numbers and size of dendritic spines, so they applied the anesthetic to the cultured rat cells at concentrations and durations (up to 60 minutes) that are frequently used during surgery.
“We observed detectable decreases in dendritic spine numbers and shape within as little as 10 minutes,” said Halpain. “However this spine loss and shrinkage was reversible after the anesthetic was washed out of the culture.”
“Our study was reassuring in the sense that the effects are not irreversible and this fits in with known clinical effects,” said Hemmings. “For the most part, we find that the effects are reversible.”
“We clearly see an effect—a very marked effect on the dendritic spines—from use of this drug that was reversible, suggesting that it is not a toxic effect, but something more relevant to the pharmacological actions of the drug,” he added. “Connecting what we found to the cognitive effects of isoflurane will require much more detailed analysis.”
The team plans to follow up its study with future experiments to probe the molecular mechanisms and long-lasting consequences of isoflurane’s effects on neuron synapses and examine other commonly-used anesthetics for surgery.
How neuro cells turn cancerous
Scientists from the Sloan-Kettering Institute for Cancer Research in New York with the help of Plymouth University Peninsula Schools of Medicine and Dentistry have completed research which for the first time brings us nearer to understanding how some cells in the brain and nervous system become cancerous.
The results of their study are published in the prestigious journal Cancer Cell.
The research team led by Sloan-Kettering researchers studied a tumour suppressor called Merlin.
The results of the study have identified a new mechanism whereby Merlin suppresses tumours, and that the mechanism operates within the nucleus. The research team has discovered that unsuppressed tumour cells increase via a core signalling system, the hippo pathway, and they have identified the route and method by which this signalling occurs.
By identifying the signalling system and understanding how, when present, Merlin suppresses it, the way is open for research into drug therapies which may suppress the signalling in a similar way to Merlin.
Tumour suppressors exist in cells to prevent abnormal cell division in our bodies. The loss of Merlin leads to tumours in many cell types within our nervous systems. There are two copies of a tumour suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin can be caused by random loss of both copies in a single cell, causing sporadic tumours, or by inheriting one abnormal copy and losing the second copy throughout our lifetime as is seen in the inherited condition of neurofibromatosis type 2 (NF2).
No effective therapy for these tumours exists, other than repeated invasive surgery aiming at a single tumour at a time and which is unlikely to eradicate the full extent of the tumours, or radiotherapy.
Professor Oliver Hanemann, Director of the Institute of Translational and Stratified Medicine at Plymouth University Peninsula Schools of Medicine and Dentistry, and who led the Plymouth aspect of the study, commented:
“We have known for some time that the loss of the tumour suppressor Merlin resulted in the development of nervous system tumours, and we have come tantalisingly close to understanding how this occurs. Our joint study with colleagues at the Sloan-Kettering Institute for Cancer Research shows for the first time how this mechanism works. By understanding the mechanism, we can use this knowledge to develop effective drug therapies – in some cases adapting existing drugs – to treat patients for whom current therapies are limited and potentially devastating.”
(Source: www5.plymouth.ac.uk)
Researchers find epigenetic tie to neuropsychiatric disorders
Dysfunction in dopamine signaling profoundly changes the activity level of about 2,000 genes in the brain’s prefrontal cortex and may be an underlying cause of certain complex neuropsychiatric disorders, such as schizophrenia, according to UC Irvine scientists.
This epigenetic alteration of gene activity in brain cells that receive this neurotransmitter showed for the first time that dopamine deficiencies can affect a variety of behavioral and physiological functions regulated in the prefrontal cortex.
The study, led by Emiliana Borrelli, a UCI professor of microbiology & molecular genetics, appears online in the journal Molecular Psychiatry.
“Our work presents new leads to understanding neuropsychiatric disorders,” Borrelli said. “Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA.”
Dopamine is a neurotransmitter that acts within certain brain circuitries to help manage functions ranging from movement to emotion. Changes in the dopaminergic system are correlated with cognitive, motor, hormonal and emotional impairment. Excesses in dopamine signaling, for example, have been identified as a trigger for neuropsychiatric disorder symptoms.
Borrelli and her team wanted to understand what would happen if dopamine signaling was hindered. To do this, they used mice that lacked dopamine receptors in midbrain neurons, which radically affected regulated dopamine synthesis and release.
The researchers discovered that this receptor mutation profoundly altered gene expression in neurons receiving dopamine at distal sites in the brain, specifically in the prefrontal cortex. Borrelli said they observed a remarkable decrease in expression levels of some 2,000 genes in this area, coupled with a widespread increase in modifications of basic DNA proteins called histones – particularly those associated with reduced gene activity.
Borrelli further noted that the dopamine receptor-induced reprogramming led to psychotic-like behaviors in the mutant mice and that prolonged treatment with a dopamine activator restored regular signaling, pointing to one possible therapeutic approach.
The researchers are continuing their work to gain more insights into the genes altered by this dysfunctional dopamine signaling.
(Source: news.uci.edu)
Could boosting brain cells’ appetites fight disease? New research shows promise
Deep inside the brains of people with dementia and Lou Gehrig’s disease, globs of abnormal protein gum up the inner workings of brain cells – dooming them to an early death.
But boosting those cells’ natural ability to clean up those clogs might hold the key to better treatment for such conditions.
That’s the key finding of new research from a University of Michigan Medical School physician scientist and his colleagues in California and the United Kingdom. They reported their latest findings this week in the journal Nature Chemical Biology.
Though the team showed the effect worked in animals and human neurons from stem cells, not patients, their discoveries point the way to find new medicines that boost the protein-clearing cleanup process.
The work also shows how an innovative microscope technique can help researchers see what’s going on inside brain cells, as they labor to clear out the protein buildup.
The researchers focused on a crucial cell-cleaning process called autophagy – a hot topic in basic medical research these days, as scientists discover its important role in many conditions. In autophagy, cells bundle unwanted materials up, break them down and push the waste products out.
In the newly published research, the team showed how the self-cleaning capacity of some brain cells gets overwhelmed if the cells make too much of an abnormal protein called TDP43. They found that cells vary greatly in how quickly their autophagy capacity gets swamped.
In brain cells that were made from stem cells derived from ALS patients, treatment with two drugs that stimulate autophagy led to longer cell survival (middle two lines).
But they also showed how three drugs that boost autophagy – speeding up the clean-out process – could keep the brain cells alive longer.
Longer-living, TDP43-clearing brain cells are theoretically what people with Lou Gehrig’s disease (amyotrophic lateral sclerosis or ALS) and certain forms of dementia (called frontotemporal) need. But only further research will show for sure.
Sami Barmada, M.D., Ph.D., the U-M neurologist and scientist who is first author of the new study, says the new findings are encouraging – and so is the success of a microscope technique used in the research. His new lab, in the U-M Department of Neurology, is continuing to refine ways to view the inner workings of nerve cells.
“Using this new visualization technique, we could truly see how the protein was being cleared, and therefore which compounds could enhance the pace of clearance and shorten the half-life of TDP43 inside cells,” he says. “This allowed us to see that increased autophagy was directly related to improved cell survival.”
Barmada worked on the team at the Gladstone Institutes and the University of California San Francisco headed by Steven Finkbeiner, M.D., Ph.D., that published the new findings. The team used stem cells derived from the cells of people who have ALS to grow neurons and astrocytes – the two types of brain cell most crucial to normal brain function.
Because he both sees patients in clinic and studies neurological disease in the laboratory, Barmada brings a special perspective to the research.
At U-M, he specializes in treating patients who have neurological diseases that affect both thinking and muscle control. About a third of ALS patients develop signs of frontotemporal dementia, also called FTD – and about 10 percent of people with FTD also have a motor neuron disease that affects their brain’s ability to control muscle movement.
One of the drugs tested in the study, an antipsychotic drug developed in the 1960s to treat people with schizophrenia, had actually shown some anti-dementia promise in human ALS patients, but comes with many side effects. Barmada notes that Finkbeiner’s team at the Gladstone Institute is already working to identify other compounds that could produce the effect with fewer side effects.
Interestingly, small studies have suggested that people with schizophrenia who take antipsychotic drugs are much less likely to develop ALS.
Barmada’s work at U-M now focuses on the connection between brain cells’ ability to clear abnormal proteins. He also studies the cells’ regulation of RNA molecules created as part of expressing protein-encoding genes. Looking further upstream in the protein-producing process could yield further clues to why disease develops and what can be done about it, he says.
(Source: uofmhealth.org)
Schizophrenia-Associated Gene Variation Affects Brain Cell Development
Johns Hopkins researchers have begun to connect the dots between a schizophrenia-linked genetic variation and its effect on the developing brain. As they report July 3 in the journal Cell Stem Cell, their experiments show that the loss of a particular gene alters the skeletons of developing brain cells, which in turn disrupts the orderly layers those cells would normally form.
(Image caption: Left, human neural stem cells form rosettes as they grow into different cell types, with ringlike patterns of PKCλ protein in the center. A neural rosette with a 15q11.2 microdeletion, a risk factor for schizophrenia, appears disorganized and lacks the ringlike PKCλ protein structure, right, suggesting that this risk factor acts early in the neurodevelopmental process. Credit: Ki-Jun Yoon/Johns Hopkins Medicine)
“This is an important step toward understanding what physically happens in the developing brain that puts people at risk of schizophrenia,” says Guo-li Ming, M.D., Ph.D., a professor of neurology and neuroscience in the Johns Hopkins University School of Medicine’s Institute for Cell Engineering.
While no single genetic mutation is known to cause schizophrenia, so-called genome wide association studies have identified variations that are more common in people with the condition than in the general population. One of these is a missing piece from an area of the genome labeled 15q11.2. “While the deletion is linked to schizophrenia, having extra copies of this part of the genome raises the risk of autism,” notes Ming.
For the new study, Ming’s research group, along with that of her husband and collaborator, neurology and neuroscience professor Hongjun Song, Ph.D., used skin cells from people with schizophrenia who were missing part of 15q11.2 on one of their chromosomes. (Because everyone carries two copies of their genome, the patients each had an intact copy of 15q11.2 as well.)
The researchers grew the human skin cells in a dish and coaxed them to become induced pluripotent stem cells, and then to form neural progenitor cells, a kind of stem cell found in the developing brain.
“Normally, neural progenitors will form orderly rings when grown in a dish, but those with the deletion didn’t,” Ming says. To find out which of the four known genes in the missing piece of the genome were responsible for the change, the researchers engineered groups of progenitors that each produced less protein than normal from one of the suspect genes. The crucial ingredient in ring formation turned out to be a gene called CYFIP1.
The team then altered the genomes of neural progenitors in mouse embryos so that they made less of the protein created by CYFIP1. The brain cells of the fetal mice turned out to have similar defects in structure to those in the dish-grown human cells. The reason, the team found, is that CYFIP1 plays a role in building the skeleton that gives shape to each cell, and its loss affects spots called adherens junctions where the skeletons of two neighboring cells connect.
Having less CYFIP1 protein also caused some neurons in the developing mice to end up in the wrong layer within the brain. “During development, new neurons get in place by ‘climbing’ the tendrils of neural progenitor cells,” Ming says. “We think that disrupted adherens junctions don’t provide a stable enough anchor for neural progenitors, so the ‘rope’ they form doesn’t quite get new neurons to the right place.”
The researchers say they also found that CYFIP1 is part of a complex of proteins called WAVE, which is key to building the cellular skeleton.
Many people with a CYFIP1 deletion do not get schizophrenia, so the team suspected the condition was more likely to arise in people with a second defect in the WAVE complex.
Analyzing data from genomewide association studies, they found a variation in the WAVE complex signaling gene ACTR2/Arp2 that, combined with the CYFIP1 deletion, increased the risk of schizophrenia more than either genetic change by itself.
In adding to science’s understanding of schizophrenia, the study also shows how other mental illnesses might be similarly investigated, the researchers say. “Using induced pluripotent stem cells from people with schizophrenia allowed us to see how their genes affected brain development,” says Song. “Next, we’d like to investigate what effects remain in the mature brain.”
(Source: hopkinsmedicine.org)
Fatal cell malfunction ID’d in Huntington’s disease
Researchers believe they have learned how mutations in the gene that causes Huntington’s disease kill brain cells, a finding that could open new opportunities for treating the fatal disorder. Scientists first linked the gene to the inherited disease more than 20 years ago.
Huntington’s disease affects five to seven people out of every 100,000. Symptoms, which typically begin in middle age, include involuntary jerking movements, disrupted coordination and cognitive problems such as dementia. Drugs cannot slow or stop the progressive decline caused by the disorder, which leaves patients unable to walk, talk or eat.
Lead author Hiroko Yano, PhD, of Washington University School of Medicine in St. Louis, found in mice and in mouse brain cell cultures that the disease impairs the transfer of proteins to energy-making factories inside brain cells. The factories, known as mitochondria, need these proteins to maintain their function. When disruption of the supply line disables the mitochondria, brain cells die.
“We showed the problem could be fixed by making cells overproduce the proteins that make this transfer possible,” said Yano, assistant professor of neurological surgery, neurology and genetics. “We don’t know if this will work in humans, but it’s exciting to have a solid new lead on how this condition kills brain cells.”
The findings are available online in Nature Neuroscience.
Huntington’s disease is caused by a defect in the huntingtin gene, which makes the huntingtin protein. Life expectancy after initial onset is about 20 years.
Scientists have known for some time that the mutated form of the huntingtin protein impairs mitochondria and that this disruption kills brain cells. But they have had difficulty understanding specifically how the gene harms the mitochondria.
For the new study, Yano and collaborators at the University of Pittsburgh worked with mice that were genetically modified to simulate the early stages of the disorder.
Yano and her colleagues found that the mutated huntingtin protein binds to a group of proteins called TIM23. This protein complex normally helps transfer essential proteins and other supplies to the mitochondria. The researchers discovered that the mutated huntingtin protein impairs that process.
The problem seems to be specific to brain cells early in the disease. At the same point in the disease process, the scientists found no evidence of impairment in liver cells, which also produce the mutated huntingtin protein.
The researchers speculated that brain cells might be particularly reliant on their mitochondria to power the production and recycling of the chemical signals they use to transmit information. This reliance could make the cells vulnerable to disruption of the mitochondria.
Other neurodegenerative conditions, including Alzheimer’s disease and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, have been linked to problems with mitochondria. Scientists may be able to build upon these new findings to better understand these disorders.
(Source: news.wustl.edu)
Scientists show how bigger brains could help us see better
It has become increasingly common to hear reports that big brains are not necessary, or even an evolutionary fluke. However, the new article found that increases in the size of brain areas, such as the visual cortex, are an essential element of evolution.
As part of the study, the researchers found that an increase in the size of the visual part of the brain in different primate species, including humans, apes, and monkeys, is associated with enhanced visual processing.
It is controversial whether overall brain size can predict intelligence. However the size of specialised areas within the brain is associated with specific changes in behaviour such as reducing the susceptibility to visual illusions and increasing the visual acuity or fine details that can be seen.
First author, Dr Alexandra de Sousa explained: “Primates with a bigger visual cortex have better visual resolution, the precision of vision, and reduced visual illusion strength. In essence, the bigger the brain area, the better the visual processing ability.
“The size of brain areas predicts not only the number of neurons (brain cells) in that area, but also the likelihood of connections between neurons. These connections allow for increasingly complex computations to be made that allow for more accurate, and more difficult, visual perception.”
Co-author, Dr Michael Proulx, Senior Lecturer (Associate Professor) in Psychology, added: “This paper is a novel attempt to bring together the micro and macro anatomy of the brain with behaviour. We link visual abilities, the size of brain areas, and the number of neurons that make up those brain areas to provide a framework that ties brain structure and function together.
“The theory of brain size that we discuss can be tested in the future with more behavioural tests of other species, gathering more comparative neuroanatomical data, and by testing other senses and multi-sensory perception, too. We might be able to even predict how well extinct species could sense the world based on fossil data.”
For the study, Dr Alexandra de Sousa, an expert in brain evolution, provided brain size measurements from her and other’s neuroanatomical research. Dr Michael Proulx, an expert in perception, found psychological studies of visual illusions and visual acuity in the same species or general of animals.
The paper ‘What can volumes reveal about human brain evolution? A framework for bridging behavioral, histometric and volumetric perspectives’ is published today in Frontiers in Neuroanatomy – an online, open access journal.
(Source: bath.ac.uk)
Neuroscientists explain how mutated X-linked mental retardation protein impairs neuronal function
There are new clues about malfunctions in brain cells that contribute to intellectual disability and possibly other developmental brain disorders.
(Image caption: False color image of a mouse hippocampal neuron (cell
body is at lower right) with branchlike dendrites that provide surfaces at which projections from other neurons can connect, by forming synapses. Van Aelst and colleagues have shown that when the OPHN1 protein is mutated, interfering with its ability to interact with another protein called Homer1b/c, AMPA receptors don’t recycle to the surface at synapses at the rate they normally do. This adversely impacts synaptic plasticity, the process by which neurons adjust the strength of their connections. Such pathology may play a role in X-linked mental retardation.)
Professor Linda Van Aelst of Cold Spring Harbor Laboratory (CSHL) has been scrutinizing how the normal version of a protein called OPHN1 helps enable excitatory nerve transmission in the brain, particularly at nerve-cell docking ports containing AMPA receptors (AMPARs). Her team’s new work, published June 24 in the Journal of Neuroscience, provides new mechanistic insight into how OPHN1 defects can lead to impairments in the maturation and adjustment of synaptic strength of AMPAR-expressing neurons, which are ubiquitous in the brain and respond to the excitatory neurotransmitter glutamate.
Mutations in a gene called oligophrenin-1 (OPHN1) – located on the X chromosome – have previously been linked to X-linked intellectual disability (also known as X-linked mental retardation), a condition that affects boys disproportionately and could account for as much as one-fifth of all intellectual disability among males.
Several different mutations in the OPHN1 gene have been identified to date, all of which perturb nerve cells’ manufacture of OPHN1 protein. Previously, Van Aelst and colleagues demonstrated that OPHN1 has a vital role in synaptic plasticity, the process through which adjacent nerve cells adjust the strength of their connections. Cells in the brain are constantly adjusting connection strength as they respond to streams of stimuli.
The new discovery shows how OPHN1 is involved in the trafficking of AMPARs, an essential feature of plasticity in neurons. Neurons move receptors away from synapses into their interior and then back to the surface of synapses to control connection strength. At the synaptic surface, receptors provide an opportunity for the docking of neurotransmitters, in this case glutamate molecules. After a cell has fired, surface receptors are typically brought back into the interior, where they are recycled for future use.
When OPHN1 is misshapen or missing due to genetic mutation, the CSHL team demonstrated, it can no longer properly perform its role in receptor recycling, thus also impairing neurons’ ability to maintain strong long-term connections with their neighbors, called long-term potentiation.
Van Aelst’s new experiments explain how OPHN1 in complex with another protein called Homer1b/c should normally interact with an area called the endocytic zone (EZ) to provide a pool of AMPARs to be brought to the synapse at a location called the post-synaptic density (PSD). When OPHN1 is mutated, the pool does not form and receptors needed for strengthening synapses are not available. Long-term potentiation is impaired.
“This suggests a previously unknown way in which genetic defects in OPHN1 can lead to dysfunctions in the glutamate system,” says Dr. Van Aelst. “Our earlier studies had already shown that OPHN1 is essential in stabilizing AMPA receptors at the synapse. Together, these two essential roles suggest how defective OPHN1 protein may contribute to pathology that underlies X-linked intellectual disability.”
(Source: cshl.edu)