Visualizing Formation Of A New Synapse.

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ScienceDaily (June 25, 2009) — A protein called neuroligin that is implicated in some forms of autism is critical to the construction of a working synapse, locking neurons together like "molecular Velcro," a study lead by a team of UC Davis researchers has found.

Published online in the June issue of the journal Neural Development, the study is accompanied by groundbreaking images that are the first to show two neurons coming together using neuroligin to construct a new synapse.
"Previous research has suggested that neuroligin is critical for the formation and stabilization of synapses," said Kimberley McAllister, an associate professor of neurology in the UC Davis School of Medicine and a researcher at the UC Davis Center for Neuroscience. "Our work suggests that neuroligin is one of the first molecules to be recruited to new synapses and that it also acts as Velcro to strengthen those new connections."
Neuroligin is a member of a family of four protein molecules that bind to another family of proteins, the β-neurexins, across synapses. During the past decade, scientists have observed that neuroligin is critical for synapse formation and function, but it is only recently that a link between the two synapse-forming molecules and autism has been recognized, McAllister said.
Lead study author and UC Davis postdoctoral fellow Stephanie Barrow said that researchers had hypothesized that neuroligin could facilitate the recruitment of other proteins important in building synapses, but no one had been able to directly visualize the process. That's because synapses are less than 1 micron wide — 100 times narrower than a strand of human hair. To view the process, the researchers cultured neurons taken from newly born rats and flourescently labled the proteins — neuroligin, PSD-95 and NMDA — which are critical to synapse formation.
"We are the first to observe that neuroligin zips around dendrites (the branched projections of neurons) before synapses form and can accumulate very soon after contact between cells," Barrow said.
Barrow described what the team was able to visualize: "Axons of one neuron grow toward the dendrites of neighboring neurons. As they do so, finger-like structures called filopodia extend and retract rapidly from the tip of the axons and eventually make a stable contact with the dendrite. We can then see neuroligin accumulate at these new contact sites very rapidly, possibly stabilizing adhesion between the two cells. After a few minutes, more neuroligin accumulates at this contact site, bringing NMDA receptors in with it, which is then followed by a much slower recruitment of PSD-95."
The images that accompany the study show that, indeed, the two synaptic receptor proteins, PSD-95 and NMDA, are independently recruited to the site of synapse formation once the connections are locked in place by neuroligin.
"Synapses are basically specialized sites of cell adhesion that are initially formed during development of the nervous system. Formation of viable synapses is crucial for establishing neuronal circuits that underlie behavior and cognition," said study senior author Philip Washbourne, a UC Davis postdoctoral fellow when the study was initiated and now an assistant professor of biology at the University of Oregon.
McAllister and Barrow are continuing to capture images of the dynamics of other important molecules during synapse formation. Their goal is to create a virtual cinematic representation that includes many of the molecules that play important roles in the formation of a normal, working synapse.
"Many people think that improper synapse formation leads to the symptoms of autism," McAllister said. "This research will allow us to learn more about how synapses form to better understand what aspects of synapse formation might be altered in the disorder."
Other study authors include Faten El-Sabeawy of UC Davis, Eliana Clark, formerly of UC Davis, and University of Oregon postdoctoral fellow John Constable.
The study was funded by the Pew Charitable Trusts, the National Eye Institute, the John Merck Fund, a UC Davis Vision Science Training Grant, the Whitehall Foundation and Autism Speaks.
Adapted from materials provided by University of California - Davis - Health System.

Social Competition May Be Reason For Bigger Brain

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ScienceDaily (June 23, 2009) — For the past 2 million years, the size of the human brain has tripled, growing much faster than other mammals. Examining the reasons for human brain expansion, University of Missouri researchers studied three common hypotheses for brain growth: climate change, ecological demands and social competition. The team found that social competition is the major cause of increased cranial capacity.

To test the three hypotheses, MU researchers collected data from 153 hominid (humans and our ancestors) skulls from the past 2 million years. Examining the locations and global climate changes at the time the fossil was dated, the number of parasites in the region and estimated population density in the areas where the skulls were found, the researchers discovered that population density had the biggest effect on skull size and thus cranial capacity.
"Our findings suggest brain size increases the most in areas with larger populations and this almost certainly increased the intensity of social competition," said David Geary, Curator's Professor and Thomas Jefferson Professor of Psychosocial Sciences in the MU College of Arts and Science. "When humans had to compete for necessities and social status, which allowed better access to these necessities, bigger brains provided an advantage."
The researchers also found some credibility to the climate-change hypothesis, which assumes that global climate change and migrations away from the equator resulted in humans becoming better at coping with climate change. But the importance of coping with climate was much smaller than the importance of coping with other people.
"Brains are metabolically expensive, meaning they take lots of time and energy to develop and maintain, making it so important to understand why our brains continued to evolve faster than other animals," said Drew Bailey, MU graduate student and co-author of the study. "Our research tells us that competition, whether healthy or not, sets the stage for brain evolution."
Journal reference:
David Geary and Drew Bailey. Hominid Brain Evolution. Human Nature, (in press)
Adapted from materials provided by University of Missouri-Columbia.

Brain Detects Happiness More Quickly Than Sadness

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ScienceDaily (June 21, 2009) — Our brains get a first impression of people's overriding social signals after seeing their faces for only 100 milliseconds (0.1 seconds). Whether this impression is correct, however, is another question. Now an international group of experts has carried out an in-depth study into how we process emotional expressions, looking at the pattern of cerebral asymmetry in the perception of positive and negative facial signals.

The researchers worked with 80 psychology students (65 women and 15 men) to analyze the differences between their cerebral hemispheres using the "divided visual field" technique, which is based on the anatomical properties of the visual system.
"What is new about this study is that working in this way ensures that the information is focused on one cerebral hemisphere or the other", J. Antonio Aznar-Casanova, one of the authors of the study and a researcher at the University of Barcelona (UB), tells SINC.
The results, published in the latest issue of the journal Laterality, show that the right hemisphere performs better in processing emotions. "However, this advantage appears to be more evident when it comes to processing happy and surprised faces than sad or frightened ones", the researcher points out.
"Positive expressions, or expressions of approach, are perceived more quickly and more precisely than negative, or withdrawal, ones. So happiness and surprise are processed faster than sadness and fear", explains Aznar-Casanova.
The two faces of the brain
This research study adds to previous ones, which had revealed asymmetries in the way the brain processes emotions, and enriches the international debate in cognitive-emotional neuroscience in terms of how to define the exact way in which human beings process these facial expressions.
People make deductions from the expressions on people's faces. "These inferences can strongly influence election results or the sentences given in trials, and have been studied before in fields such as criminology and the pseudoscience of physiognomy", the neuroscientist tells SINC.
Two theories are currently "competing" to explain the pattern of cerebral asymmetry in processing emotions. The older one postulates the dominance of the right hemisphere in the processing of emotions, while the second is based on the approach-withdrawal hypothesis, which holds that the pattern of cerebral asymmetry depends upon the emotion in question, in other words that each hemisphere is better at processing particular emotions (the right, withdrawal, and the left, approach).
"Today there is scientific evidence in favour of both these theories, but there is a certain consensus in favour of the lateralisation of emotional processing predicted by the approach-withdrawal hypothesis", concludes Aznar-Casanova.
Journal reference:
Alves et al. Patterns of brain asymmetry in the perception of positive and negative facial expressions. Laterality Asymmetries of Body Brain and Cognition, 2008; 14 (3): 256 DOI: 10.1080/13576500802362927
Adapted from materials provided by Plataforma SINC.

First Image Of Memories Being Made

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ScienceDaily (June 19, 2009) — The ability to learn and to establish new memories is essential to our daily existence and identity; enabling us to navigate through the world. A new study by researchers at the Montreal Neurological Institute and Hospital (The Neuro), McGill University and University of California, Los Angeles has captured an image for the first time of a mechanism, specifically protein translation, which underlies long-term memory formation.

The finding provides the first visual evidence that when a new memory is formed new proteins are made locally at the synapse - the connection between nerve cells - increasing the strength of the synaptic connection and reinforcing the memory. The study published in Science, is important for understanding how memory traces are created and the ability to monitor it in real time will allow a detailed understanding of how memories are formed.
When considering what might be going on in the brain at a molecular level two essential properties of memory need to be taken into account. First, because a lot of information needs to be maintained over a long time there has to be some degree of stability. Second, to allow for learning and adaptation the system also needs to be highly flexible.
For this reason, research has focused on synapses which are the main site of exchange and storage in the brain. They form a vast but also constantly fluctuating network of connections whose ability to change and adapt, called synaptic plasticity, may be the fundamental basis of learning and memory.
"But, if this network is constantly changing, the question is how do memories stay put, how are they formed? It has been known for some time that an important step in long-term memory formation is "translation", or the production, of new proteins locally at the synapse, strengthening the synaptic connection in the reinforcement of a memory, which until now has never been imaged," says Dr. Wayne Sossin, neuroscientist at The Neuro and co-investigator in the study. "Using a translational reporter, a fluorescent protein that can be easily detected and tracked, we directly visualized the increased local translation, or protein synthesis, during memory formation. Importantly, this translation was synapse-specific and it required activation of the post-synaptic cell, showing that this step required cooperation between the pre and post-synaptic compartments, the parts of the two neurons that meet at the synapse. Thus highly regulated local translation occurs at synapses during long-term plasticity and requires trans-synaptic signals."
Long-term memory and synaptic plasticity require changes in gene expression and yet can occur in a synapse-specific manner. This study provides evidence that a mechanism that mediates this gene expression during neuronal plasticity involves regulated translation of localized mRNA at stimulated synapses. These findings are instrumental in establishing the molecular processes involved in long-term memory formation and provide insight into diseases involving memory impairment.
This study was funded by the National Institutes of Health, the WM Keck Foundation and the Canadian Institutes of Health Research.
Adapted from materials provided by McGill University, via EurekAlert!, a service of AAAS.

How Young Mice Phone Home: Study Gives Clue To How Mothers' Brains Screen For Baby Calls

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ScienceDaily (June 11, 2009) — Emory University researchers have identified a surprising mechanism in the brains of mother mice that focuses their awareness on the calls of baby mice. Their study, published June 11 in Neuron, found that the high-frequency sounds of mice pups stand out in a mother's auditory cortex by inhibiting the activity of neurons more attuned to lower frequency sounds.

"Previous research has focused on how the excitation of neurons can detect or interpret sounds, but this study shows the key role that inhibition may play in real situations," said Robert Liu, assistant professor of biology and senior author of the study.
In 2007, Liu and colleagues were the first to demonstrate that the behavioral context in which communication sounds are heard affects the brain's ability to detect, discriminate and respond to them. Specifically, the researchers found that the auditory neurons of female mice that had given birth were better at detecting and discriminating vocalizations from mice pups than auditory neurons in virgin females.
Experiments on awake mice
While that experiment was done with anesthetized mice, the current study by Liu's lab is the first to record the activity of neurons in the auditory cortex of awake mice. Both female mice that had given birth and virgin female mice with no experience caring for mice pups were used in the study.
When exposed to the high-frequency whistles of mice pups, which fall into the 60 to 80 kilohertz range, a large area of neurons in the auditory cortex of the mother mice was more strongly inhibited than in the virgin mice. The pattern of excitation of neurons was similar, however, for both the mothers and virgins.
"Something different is happening in the mothers' brains when they are processing the same sound, and this difference is consistent," Liu said. "The inhibition of neurons appears to be enhancing the contrast in the sound of mice pups, so they stand out more in the acoustic environment."
Showing neural plasticity
Liu's research focuses on how the brain evolves to process sounds in the natural environment. "By understanding normal functioning of the auditory processes in the brain, then we can begin to understand what is breaking down in disease situations, such as following a stroke or brain lesion," he said.
Until recently, it had been widely assumed that the auditory cortex acted simply as a static filter, and that areas downstream in the brain did the complex task of learning to parse meaning from sounds.
"What our experiments help demonstrate is that even at this relatively early stage of cortical sound processing, responses are dynamic," Liu said. "The auditory cortex has plasticity, so that sounds that become behaviorally relevant to us can get optimized."
More research is needed, he added, to determine whether the changes in the brains of mother mice is due to hormonal shifts, the behavioral experience of caring for pups, or both.
The study authors include Edgar Galindo-Leon, a post-doctoral fellow in Liu's lab, and Frank Lin, a graduate student in the lab. Their research was funded by the National Institute for Deafness and Communication Disorders and the NSF Center for Behavioral Neuroscience.
Journal reference:
Edgar E. Galindo-Leon, Frank G. Lin, Robert C. Liu. Inhibitory Plasticity in a Lateral Band Improves Cortical Detection of Natural Vocalizations. Neuron, 2009; DOI: 10.1016/j.neuron.2009.05.001
Adapted from materials provided by Emory University, via EurekAlert!, a service of AAAS.

Needle Biopsies Safe In 'Eloquent' Areas Of Brain, Study Suggests

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ScienceDaily (June 5, 2009) — After a review of 284 cases, specialists at the Brain Tumor Center at the University of Cincinnati (UC) Neuroscience Institute have concluded that performing a stereotactic needle biopsy in an area of the brain associated with language or other important functions carries no greater risk than a similar biopsy in a less critical area of the brain.

The retrospective study, led by Christopher McPherson, MD, director of the division of surgical neuro-oncology at UC and a Mayfield Clinic neurosurgeon, was published online in May in the Journal of Neurosurgery.
The UC study compared the complication rates of stereotactic biopsies in functional, or “eloquent,” areas of the brain that were associated with language, vision, and mobility to areas that were not associated with critical functions. Eloquent areas included the brainstem, basal ganglia, corpus callosum, motor cortex, thalamus, and visual cortex. Complications were defined as the worsening of existing neurological deficits, seizures, brain hemorrhaging and death.
“Needle biopsies in eloquent areas have generally been acknowledged to be safe, because the needle causes only a small amount of disruption to the brain,” McPherson explains. “But until now, researchers had not actually documented that biopsies in eloquent areas were as safe as those in non-eloquent areas.”
To make that comparison, McPherson’s team studied records of 284 stereotactic needle biopsies performed by 19 Mayfield Clinic neurosurgeons between January 2000 and December 2006. In the 160 biopsies that involved eloquent areas of the brain, complications occurred in nine cases (5.6 percent of the total). In the 124 biopsies that involved non-eloquent areas, complications occurred in 10 cases (8.1 percent). The difference was not statistically significant.
Overall, 19 of the 284 patients, or 6.7 percent, suffered complications. Thirteen of those patients recovered completely or somewhat from their complications, while six (2.1 percent of the total number of patients biopsied) experienced permanent neurological decline.
“Diagnosing and treating brain tumors always carries risk,” McPherson says. “Within that context, the results of this large sampling of biopsies are encouraging overall and reinforce our belief that stereotactic biopsy is a valuable diagnostic tool. Stereotactic biopsy is a safe way for us to remove a tissue sample for the diagnosis of a brain tumor, even when the tumor is in a challenging and dangerous part of the brain.”
Additional co-authors of the study are Ronald Warnick, MD, director of the UC Brain Tumor Center and chairman of the Mayfield Clinic; James Leach, MD, associate professor of neuroradiology at UC and a neuroradiologist at Cincinnati Children’s Hospital Medical Center and the UC Neuroscience Institute; and Ellen Air, MD, PhD, a resident in the UC Department of Neurosurgery.
Journal reference:
Air et al. Comparing the risks of frameless stereotactic biopsy in eloquent and noneloquent regions of the brain: a retrospective review of 284 cases. Journal of Neurosurgery, 2009; 090501065138063 DOI: 10.3171/2009.3.JNS081695
Adapted from materials provided by University of Cincinnati Academic Health Center.