Brain cells known as neurons process information by joining into complex networks, transmitting signals to each other across junctions called synapses. But "neurons don't just connect to other neurons," emphasizes Z. Josh Huang, Ph.D., "in a lot of cases, they connect to very specific partners, at particular spots." Dr. Huang, a professor at Cold Spring Harbor Laboratory (CSHL), leads a team that has identified molecules guiding this highly specific neuronal targeting in the developing brains of mice.
The researchers report in PLoS Biology that in some cases, these molecular guides -- non-signaling brain cells known as glia -- form a kind of scaffold. This scaffold, in turn, directs the growth of nerve fibers and their connections between specific types of neurons.
As they learn through research like this how the brain develops its complex wiring, the scientists hope they can clarify what goes wrong in disorders like autism.
Science & Technology
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Sculpture depicts overhead view of brain’s cortex (copper) and white matter core.
Sculpture depicts overhead view of brain’s cortex (copper) and white matter core.
Imagine if we could peek through the skull to see what makes one brain smarter than another. Or to discover whether hidden traits might be driving a person's schizophrenia or dyslexia. A new kind of imaging technique is helping scientists observe such evidence, and it is revealing a surprise: intelligence, and a variety of mental syndromes, may be influenced by tracts within the brain made exclusively of white matter.
Gray matter, the stuff between your ears your teachers chided you about, is where mental computation takes place and memories are stored. This cortex is the "topsoil" of the brain; it is composed of densely packed neuronal cell bodies - the decision-making parts of nerve cells, or neurons.
Underneath it, however, is a bedrock of "white matter" that fills nearly half of the human brain - a far larger percentage than found in the brains of other animals.
© Rockefeller University
Warm glow. By exploiting a cell's heat shock response, scientists use transgenes to express green fluorescent protein exclusively in amphid sheath cells, a type of nervous system cell in C. elegans. These cells do not fluoresce until scientists raise the temperature to 34 degrees Celsius.
Warm glow. By exploiting a cell's heat shock response, scientists use transgenes to express green fluorescent protein exclusively in amphid sheath cells, a type of nervous system cell in C. elegans. These cells do not fluoresce until scientists raise the temperature to 34 degrees Celsius.
By exploiting the heat shock response, an ancient mechanism that protects cells from dangerously high temperatures, researchers have developed a new method to introduce foreign genes, called transgenes, into an organism and control when and where these transgenes are expressed. Unlike other techniques, which are labor intensive and inefficient, this new method makes controlling transgene expression as easy as turning the dial on an oven.
During heat shock, a protein called heat shock factor-1 travels from a cell's cytoplasm to the nucleus, where it binds to a specific sequence of DNA. This interaction initiates the transcription of heat shock protein, a shield that deflects excess heat from cells and protects them from damage. Since these two proteins are expressed at a specific time - when organisms experience heat shock at a specific temperature - scientists had long designed transgenes to be expressed the moment heat shock factor-1 binds to this sequence of DNA.
However, while scientists could know when this transgene was expressed, they couldn't limit its expression in specific cell types and study a particular protein's effect on them. To do so, they would have to target a single cell with a laser beam until the heat shock response kicked in for the transgene to be expressed. In Caenorhabditis elegans, that's 34 degrees Celsius.
Glial cells of the nervous system, once thought to function strictly as support cells for neurons, are now thought to actively modulate them. Providing further evidence in support of this theory, researchers at the Department of Neuroscience and the Center for Neuroscience Research (CNR) at Tufts University School of Medicine (TUSM) recently identified a specific population of glial cells that is required for the control of circadian behavior in Drosophila (the fruit fly). Their findings, which confirm and extend their earlier work, are published in the August 2, 2007, issue of Neuron.
"Our results suggest that an autonomous glial mechanism may drive circadian rhythms in the activity of a Drosophila protein known as Ebony," says F. Rob Jackson, PhD, director of the CNR and professor of neuroscience at TUSM. "Ebony activity and the glia containing that activity" explains Jackson, "function independently of, or in concert with, other brain cells (neurons) to control circadian behavior."
"Most organisms," says Jackson, "from Drosophila to humans, have the ability to adapt the timing of behavior or other processes to environmental cycles using an intrinsic time-keeping device called a circadian clock."
"Our results suggest that an autonomous glial mechanism may drive circadian rhythms in the activity of a Drosophila protein known as Ebony," says F. Rob Jackson, PhD, director of the CNR and professor of neuroscience at TUSM. "Ebony activity and the glia containing that activity" explains Jackson, "function independently of, or in concert with, other brain cells (neurons) to control circadian behavior."
"Most organisms," says Jackson, "from Drosophila to humans, have the ability to adapt the timing of behavior or other processes to environmental cycles using an intrinsic time-keeping device called a circadian clock."
The insulating myelin sheath enwrapping the cable-like axons of nerve cells is the major target of attack of the immune system in multiple sclerosis. Such attack causes neural short-circuits that give rise to the muscle weakness, loss of coordination, and speech and visual loss in the disease.
Now, Douglas Fields of the National Institute of Child Health and Human Development and his colleagues have reported in Neuron that supporting cells called astrocytes in the central nervous system (CNS) promote myelination by releasing an immune system molecule that triggers myelin-forming cells to action. The finding, they say, "may offer new approaches to treating demyelinating diseases."
Astrocytes, so named because of their star-like shape, are the most prominent supporting cells in the nervous system. They provide critical regulatory molecules that enable nerve cells to develop and connect properly.
Now, Douglas Fields of the National Institute of Child Health and Human Development and his colleagues have reported in Neuron that supporting cells called astrocytes in the central nervous system (CNS) promote myelination by releasing an immune system molecule that triggers myelin-forming cells to action. The finding, they say, "may offer new approaches to treating demyelinating diseases."
Astrocytes, so named because of their star-like shape, are the most prominent supporting cells in the nervous system. They provide critical regulatory molecules that enable nerve cells to develop and connect properly.
The key to understanding our brains may lie within a one-millimeter long worm, new research from Rockefeller University indicates. Reporting in the June issue of Developmental Cell, Shai Shaham, Ph.D., and graduate student Elliot Perens use the roundworm, C. elegans, to investigate the mysterious glial cell, which makes up 90 percent of the human brain and, when it malfunctions, can contribute to diseases like Parkinson's disease and schizophrenia.
Studying glial cells is technically difficult as they are essential for neuronal cell survival: disturbing them in any way puts the organism's life in jeopardy. Shaham and Perens show that worms are the perfect model system to study the function of these cells in the nervous system, because the glial cells can be manipulated and the neurons still form and function, though not entirely as normal.
"Glial cells have been traditionally hard to study in vertebrates because it is difficult to ask how they influence neurons beyond how they affect a neuron's survival," says Shaham, head of the Strang Laboratory of Developmental Genetics. "This is the first paper to take a serious crack at glial cells in C. elegans. It shows that the worm really is a great system in which to study glial cells, because we are able to get the kind of answers that could help us understand how they are functioning in the human brain."
Studying glial cells is technically difficult as they are essential for neuronal cell survival: disturbing them in any way puts the organism's life in jeopardy. Shaham and Perens show that worms are the perfect model system to study the function of these cells in the nervous system, because the glial cells can be manipulated and the neurons still form and function, though not entirely as normal.
"Glial cells have been traditionally hard to study in vertebrates because it is difficult to ask how they influence neurons beyond how they affect a neuron's survival," says Shaham, head of the Strang Laboratory of Developmental Genetics. "This is the first paper to take a serious crack at glial cells in C. elegans. It shows that the worm really is a great system in which to study glial cells, because we are able to get the kind of answers that could help us understand how they are functioning in the human brain."
Critical connections that neurons form in the brain during development turn out to rely on common but overlooked cells, called glia. These cells were known to support the neurons in adults, but had never been fingered as players in forming the connections between neurons, known as synapses.
The Stanford University School of Medicine researchers who conducted the work, led by Ben Barres, MD, PhD, professor of neurobiology, also discovered two of the proteins made by glial cells that signal synapse formation. This study, published in the Feb. 11 issue of Cell, could help researchers understand diseases such as epilepsy and addiction in which too many synapses form.
"We knew glia had a close relationship with neurons," Barres said. "We never thought the synapses would entirely fail to form without the glia." In fact, that relationship was considered so unlikely that the grant application was turned down six times because the work was considered too risky.
The Stanford University School of Medicine researchers who conducted the work, led by Ben Barres, MD, PhD, professor of neurobiology, also discovered two of the proteins made by glial cells that signal synapse formation. This study, published in the Feb. 11 issue of Cell, could help researchers understand diseases such as epilepsy and addiction in which too many synapses form.
"We knew glia had a close relationship with neurons," Barres said. "We never thought the synapses would entirely fail to form without the glia." In fact, that relationship was considered so unlikely that the grant application was turned down six times because the work was considered too risky.
Traditionally viewed as supporting actors, cells known as glia may be essential for the normal development of nerve cells responsible for hearing and balance, according to new University of Utah research. The study is reported in the January 6, 2005 issue of Neuron and is co-authored by scientists at the University of Washington.
"Using zebrafish as a model, we've demonstrated that glial cells play a previously unidentified role in regulating the development of sensory hair cell precursors -- the specialized neurons found in the inner ear of humans that make hearing possible. This research increases our understanding of how nerve cells develop and whether it may be possible to regenerate these types of cells in humans one day," said Tatjana Piotrowski, Ph.D., assistant professor of neurobiology and anatomy at the University of Utah School of Medicine.
Scientists long have known that glial cells, or simply glia, are essential for healthy nerve cells. However, in the last 10 years scientists have learned that glia aren't just "glue" holding nerve cells together. Glia communicate with each other and even influence synapse formation between neurons.
© Tatjana Piotrowski/University of Utah School of Medicine
Zebrafish Neuromasts: A) The posterior lateral line placode in a 35 h old live larva stained with Bodipy. The placode drops off neuromast precursors as it migrates posteriorly on the trunk. B) Differentiated neuromast with hair bundles in a 4 d old larva. C) 5 d old live larva in which the neuromasts are stained with the fluorescent dye Daspei.
Zebrafish Neuromasts: A) The posterior lateral line placode in a 35 h old live larva stained with Bodipy. The placode drops off neuromast precursors as it migrates posteriorly on the trunk. B) Differentiated neuromast with hair bundles in a 4 d old larva. C) 5 d old live larva in which the neuromasts are stained with the fluorescent dye Daspei.
Scientists long have known that glial cells, or simply glia, are essential for healthy nerve cells. However, in the last 10 years scientists have learned that glia aren't just "glue" holding nerve cells together. Glia communicate with each other and even influence synapse formation between neurons.
DNA that is left in the remains of long-dead plants, animals, or humans allows a direct look into the history of evolution. So far, studies of this kind on ancestral members of our own species have been hampered by scientists' inability to distinguish the ancient DNA from modern-day human DNA contamination.
Now, research by Svante Pääbo from The Max-Planck Institute for Evolutionary Anthropology in Leipzig, published online on December 31st in Current Biology - a Cell Press publication - overcomes this hurdle and shows how it is possible to directly analyze DNA from a member of our own species who lived around 30,000 years ago.
DNA - the hereditary material contained in the nuclei and mitochondria of all body cells - is a hardy molecule and can persist, conditions permitting, for several tens of thousands of years. Such ancient DNA provides scientists with unique possibilities to directly glimpse into the genetic make-up of organisms that have long since vanished from the Earth. Using ancient DNA extracted from bones, the biology of extinct animals, such as mammoths, as well as of ancient humans, such as the Neanderthals, has been successfully studied in recent years.
The ancient DNA approach could not be easily applied to ancient members of our own species. This is because the ancient DNA fragments are multiplied with special molecular probes that target certain DNA sequences.
Now, research by Svante Pääbo from The Max-Planck Institute for Evolutionary Anthropology in Leipzig, published online on December 31st in Current Biology - a Cell Press publication - overcomes this hurdle and shows how it is possible to directly analyze DNA from a member of our own species who lived around 30,000 years ago.
DNA - the hereditary material contained in the nuclei and mitochondria of all body cells - is a hardy molecule and can persist, conditions permitting, for several tens of thousands of years. Such ancient DNA provides scientists with unique possibilities to directly glimpse into the genetic make-up of organisms that have long since vanished from the Earth. Using ancient DNA extracted from bones, the biology of extinct animals, such as mammoths, as well as of ancient humans, such as the Neanderthals, has been successfully studied in recent years.
The ancient DNA approach could not be easily applied to ancient members of our own species. This is because the ancient DNA fragments are multiplied with special molecular probes that target certain DNA sequences.
Tarot readers working for the insecurity outfit McAfee are predicting that hackers will give up trying to turn over Microsoft and focus on Adobe stuff instead.
In 2009, as attacks on client software increased, cybercriminals' favourite products were Adobe Flash and Acrobat Reader. McAfee expects that next year things will get worse with attackers exploiting vulnerabilities in Flash applications via the Web and Acrobat documents via e-mail attachments.
"We expect that in 2010 Adobe product exploitation is likely to surpass that of Microsoft Office applications in the number of desktop PCs being attacked," the report said.
In 2009, as attacks on client software increased, cybercriminals' favourite products were Adobe Flash and Acrobat Reader. McAfee expects that next year things will get worse with attackers exploiting vulnerabilities in Flash applications via the Web and Acrobat documents via e-mail attachments.
"We expect that in 2010 Adobe product exploitation is likely to surpass that of Microsoft Office applications in the number of desktop PCs being attacked," the report said.
