Wrapping Up

English

Weizmann Institute Scientists reveal a mechanism for healthy nerve development, which may lead to new treatments for neurodegenerative diseases

 

In a host of neurological diseases, including multiple sclerosis (MS) and several neuropathies, the protective covering surrounding the nerves – an insulating material called myelin – is damaged.  Scientists at the Weizmann Institute of Science have now discovered an important new line of communication between nervous system cells that is crucial to the development of myelinated nerves – a discovery that may aid in restoring the normal function of the affected nerve fibers.

 

Nerve cells (neurons) have long, thin extensions called axons that can reach up to a meter and or more in length. Often, these extensions are covered by myelin, which is formed by a group of specialized cells called glia. Glial cells revolve around the axon, laying down the myelin sheath in segments, leaving small nodes of exposed nerve in between. More than just protection for the delicate axons, the myelin covering allows nerve signals to jump instantaneously between nodes, making the transfer of these signals quick and efficient.  When myelin is missing or damaged, the nerve signals can’t skip properly down the axons, leading to abnormal function of the affected nerve and often to its degeneration.

 

In research published recently in Nature Neuroscience, Weizmann Institute scientists Prof. Elior Peles, graduate student Ivo Spiegel and their colleagues in the Molecular Cell Biology Department and in the United States, have now provided a vital insight into the mechanism by which glial cells recognize and myelinate axons.

 

How do the glial cells and the axon coordinate this process? The Weizmann Institute team found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules, so called because they sit on the outer membranes of cells and help them to stick together. Peles and his team discovered that even when removed from their cells, Necl1, normally found on the axon surface, and Necl4, which is found on the glial cell membrane, adhere tightly together. When these molecules are in their natural places, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the cell interior, initiating changes needed to undertake myelination.

 

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon, and as the process of myelination begins. They observed that if Necl4 is absent in the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were contacted by glial cells did not myelinate. In the same time period, myelin wrapping was already well under way around most of the axons in the control group.
 
'What we’ve discovered is a completely new means of communication between these nervous system cells,' says Peles. 'The drugs now used to treat MS and other degenerative diseases in which myelin is affected, can only slow the disease, but not stop or cure it. Today, we can’t reverse the nerve damage caused by these disorders. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we might be able to recreate that process in patients.'

 

Prof. Elior Peles's research is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Nella and Leon Benoziyo Center for Neurological Diseases; the Kekst Family Center for Medical Genetics; The David and Fela Shapell Family Center for Genetic Disorders; the Wolgin Prize for Scientific Excellence; the National Institutes of Health (NIH); the National Multiple Sclerosis Society; the US-Israel Binational Science Foundation; and the Israel Science Foundation.

 

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

 

Weizmann Institute news releases are posted on the World Wide Web at
http://wis-wander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/.
Life Sciences
English
  • Axon
  • Elior Peles
  • Glia
  • Molecular Cell Biology
  • Multiple sclerosis

It’s Only a Game of Chance

English

A leading theory of perception has been called into question by a study at the Weizmann Institute of Science


The validity of a leading theory that has held a glimmer of hope for unraveling the intricacies of the brain has just been called into question. Dr. Ilan Lampl of the Weizmann Institute of Science’s Neurobiology Department has produced convincing evidence to the contrary. His findings recently appeared in the journal Neuron.

Cells in the central nervous system tend to communicate with each other via a wave of electrical signals that travel along neurons. The question is: How does the brain translate this information to allow us to perceive and understand the world before us?
 
It is widely believed that these electrical signals generate spiked patterns that encode different types of cognitive information. According to the theory, the brain is able to discriminate between, say, a chair and a table because each of them will generate a distinct sequence of patterns within the neural system that the brain then interprets. Upon repeated presentation of that object, its pattern is reproduced in a precise and controlled manner. Previous experiments had demonstrated repeating patterns lasting up to one second in duration.
 
But when Lampl and his colleagues recorded the activity of neurons in the brain region known as the cortex in anaesthetized rats and analyzed the data, they found no difference in the number of patterns produced or the time it takes for various patterns to repeat themselves, compared with data that was randomized. They therefore concluded that the patterns observed could not be due to the deterministically controlled mechanisms posited in the theory, but occur purely by chance.
 
The consequence of this research is likely to contribute significantly to the ongoing debate on neuronal coding. Lampl: 'Since the 1980’s, many neuroscientists believed they possessed the key for finally beginning to understand the workings of the brain. But we have provided strong evidence to suggest that the brain may not encode information using precise patterns of activity.'

Dr. Ilan Lampl’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Alhadeff Research Award; the Chais Family Foundation; the Clore Foundation; the Grodetsky Family Foundation; the Dr. Pearl H. Levine Foundation for Research in the Neurosciences; the Henry S. and Anne S. Reich Research Fund for Mental Health; and Mr. and Mrs. Gerald M. Lushing, Beverly Hills, CA. Dr. Lampl is the incumbent of the Carl and Frances Korn Career Development Chair in the Life Sciences.
Life Sciences
English
  • Cellular communication
  • Ilan Lampl
  • Neural pathway›Neural mechanism
  • Perception

Lost in Thought

English

 What happens in our brains when we “lose ourselves” in an experience?

 

Can one literally 'lose oneself' in an experience? Many theoretical models of the mind reject this notion, proposing that awareness is dependent on the mediation of areas involved in self representation – a vigilant, self-aware 'observer' network – in the human brain.
 
Prof. Rafael Malach, Ilan Goldberg and Michal Harel of the Weizmann Institute’s Neurobiology Department found a scientific means of addressing this question – by scanning the brains of volunteers performing various mental tasks. The results of their study, which were published recently in the journal Neuron, were unanticipated: When subjects were given outwardly-focused tasks that demanded their full attention, areas of the brain that relate to the self were not only inactive – they appeared to be vigorously suppressed.
 
The functional brain scans were done with an MRI (Magnetic Resonance Imaging) system, which maps brain activity by measuring changes in blood flow and oxygenation. Volunteers either viewed photos or listened to short music segments. For each stimulus, however, participants were asked to perform two different tasks. 

 

In one, 'introspective' assignment, they were asked to think about themselves and how the image or musical selection made them feel. In the second, 'sensory-motor' task, they performed quick recognition exercises – such as identifying pieces that included a trumpet’s sound. The scientists were particularly interested in certain regions in the prefrontal cortex, a part of the brain known to be involved in personality and self-knowledge, among other things. Indeed, the fMRI confirmed that these regions were active during introspection but, when subjects were absorbed in the recognition task, activity in these areas was silenced. (FMRI readings in these areas fell below those measured when subjects were resting.)
 
'It is tempting,' says Malach, 'to put these findings in a broader perspective, one that veers away from traditional western thought, with its emphasis on self-control and for which 'someone is always minding the store,' and toward more eastern perspectives, in which the 'self must be abandoned in order to fully engage with the outside world.'' On a more scientific level, their study suggests that the brain’s self-awareness centers do not function as a critical element that allows perceptual awareness of the outside world. Rather, the self-related areas of the prefrontal cortex appear to be engaged specifically when we are aware both of the sensory experience and of ourselves as the observers of this experience. When we are so occupied with the outside world as to 'forget ourselves,' only local, sensory-specific systems seem to be needed.
  
Prof. Rafael Malach’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Clore Center for Biological Physics; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions; the Edith C. Blum Foundation; and Mr. and Mrs. Irwin Green, Boca Raton, FL. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.

 

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

 

Weizmann Institute news releases are posted on the World Wide Web at
http://wis-wander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/.

Life Sciences
English
  • Brain research
  • Rafael Malach
  • Sensory stimulus
  • fMRI

Getting the Message Across

English

A team of scientists at the Weizmann Institute of Science has identified some basic principles of communication

 

How do we succeed in putting our ideas into words, so that another person can understand them? This complex undertaking involves translating an idea into a one-dimensional sequence, a string of words to be read or spoken one after the other. Of course the person on the receiving end might not get the intended point: The effective expression of one’s ideas is considered an art, or at least a desirable and important skill.

 

A team of scientists that included physicists and language researchers at the Weizmann Institute of Science recently investigated this process by applying scientific methods to some of our culture’s most successful models for effective transfer of ideas: classic writings that, by common agreement, get their messages across well. They created mathematical tools that allowed them to trace the development of ideas throughout a book. The international team included Prof. Elisha Moses of the Weizmann Institute’s Physics of Complex Systems Department and Prof. Jean-Pierre Eckmann, a frequent visitor from the University of Geneva, as well as postdoctoral fellow Enrique Alvarez Lacalle and research student Beate Dorow from the University of Stuttgart. The paper describing their research was recently published in the Proceedings of the National Academy of Sciences (PNAS).

 

Because strings of words are one-dimensional, they literally lack depth. Our minds and memories aid us in recreating complex ideas from this string. The narration 'encodes' a hierarchical structure. (An obvious hierarchical structure in a text is chapter - paragraph - sentence). The implication is that our minds decipher the encoded structure, allowing us to comprehend the abstract concept.
 
To test for an underlying structure in strings of words that are known for their ability to convey ideas, the scientists applied their mathematical tools to a number of books, including writings of Albert Einstein, Mark Twain’s Tom Sawyer, Metamorphosis by Franz Kafka and other classics of different styles and periods. They defined 'windows of attention' of around 200 words (about a paragraph) and within these windows, they identified pairs of words that frequently occurred near each other (after eliminating 'meaningless' words such as pronouns). From the resulting word lists and the frequencies with which the single words appeared in the text, the scientists’ mathematical analysis was used to construct a sort of network of 'concept vectors' – linked words that convey the principal ideas of the text.
 
Mathematically, these concept vectors can go in many directions, and reading the text can be thought of as a tour along paths in the resulting network. The multidimensional concept vectors seem to span a 'web of ideas'. The scientists’ work suggests this network is based on a tree-like hierarchy that may be a basic underpinning of language. The reader or listener can reconstruct the hierarchical structure of a text, and thus the multidimensional space of ideas, in his or her mind to grasp 'the author’s meaning.'

 

Moses: 'Philosophers from Wittgenstein to Chomsky have taught us that language plays a central evolutionary role in shaping the human brain, and that revealing the structure of language is an essential step to comprehending brain structure. Our contribution to research in this basic field is in the creation of mathematical tools that can be used to make the connection between concepts or ideas and the words used to express them, making it possible to trace in a speech or text the path of an idea in an abstract mathematical space. We can understand theoretically how the structure of the wording serves to transmit concepts and reconstruct them in the mind of the reader. A deep question that remains open is if and how the correlations we uncovered serve the aesthetics of the text.'


Prof. Elisha Moses research is supported by the Clore Center for Biological Physics; the Center for Experimental Physics; and the Rosa and Emilio Segre Research Award.

 

 

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
 
 Weizmann Institute news releases are posted on the World Wide Web at
http://wis-wander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/.

Life Sciences
English
  • Elisha Moses

Triple Code

English

Three different types of code come into play when rats sense with their whiskers


Is there a universal neural code, similar to the genetic code, in which the complexity of sense and experience can be reduced to a few simple rules? According to Prof. Ehud Ahissar of the Weizmann Institute’s Neurobiology Department, the answer might be no. He and his team have been studying how rats use their whiskers to sense their environment, and have found that the seemingly simple act of feeling out a 3-D object requires three different types of code.

Rats’ whiskers are highly developed sense organs in the normally nocturnal animals. To get a fix on their surroundings, rats whisk their whiskers back and forth as they move. Researchers had previously shown that whisking is crucial to the act of sensing, but how does the rat’s brain perceive a three-dimensional object using this movement?

Sensing begins in the neurons at the whiskers’ bases, which then fire signals off to the brain. The scientists, Marcin Szwed, Knarik Bagdasarian and Ahissar, found that in perceiving each of the three dimensions in the rat’s immediate surroundings – the horizontal, the vertical, and the radial (distance from the whisker base) – the neurons encode information in a completely different form. To sense the horizontal, for instance, the neurons fire with exact temporal precision and the timing of these signals relative to the whisking motion encodes the horizontal placement of an object. The radial, on the other hand, is encoded in quantity, specifically the number of times the neurons fire. The closer an object was to the rat’s snout, the higher the number of neuron-signaling spikes the team recorded. Height seems to be sensed through spacing: Since whisking only takes place in the horizontal plane, the researchers concluded that information about the vertical dimensions of an object is mapped out in the vertical placement of the whiskers, which are arranged grid-like on either side of the snout.

In addition to finding different codes for each dimension, the researchers noted that the nerve cells at the whiskers’ bases seemed to be specialized for the different kinds of encoding. Now the team plans to continue following the whiskers’ signals to find out how the brain interprets all three signals and melds them into one percept.

Prof. Ehud Ahissar’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Carl and Micaela Einhorn-Dominic Institute for Brain Research; the Irving B. Harris Foundation, Chicago, IL; Mrs. Esther Smidof, Switzerland; and the Edith C. Blum Foundation, New York, NY. Prof. Ahissar is the incumbent of the Helen and Sanford Diller Family Professorial Chair in Neurobiology.
Life Sciences
English
  • Ehud Ahissar
  • Neural code
  • Sensory nerves›Sensory signal
  • Whiskers

Weizmann Institute Scientists Suggest that Immune Cells Help to Maintain Cognition and Brain Cell Renewal

English

New findings that may have implications in delaying and slowing down cognitive deterioration in old age

 

REHOVOT, Israel – January 16, 2006 – A team of scientists at the Weizmann Institute of Science, led by Prof. Michal Schwartz of the Neurobiology Department, has come up with new findings that may have implications in delaying and slowing down cognitive deterioration in old age. The basis for these developments is Schwartz's team's observations, published today in the February issue of Nature Neuroscience, that immune cells contribute to maintaining the brain’s ability to maintain cognitive ability and cell renewal throughout life.
 
Until quite recently, it was generally believed that each individual is born with a fixed number of nerve cells in the brain, and that these cells gradually degenerate and die during the person's lifetime and cannot be replaced. This theory was disproved when researchers discovered that certain regions of the adult brain do in fact retain their ability to support and promote cell renewal (neurogenesis) throughout life, especially under conditions of mental stimuli and physical activity. One such brain region is the hippocampus, which subserves certain memory functions. But how the body delivers the message instructing the brain to step up its formation of new cells is yet unknown.

 

The central nervous system (CNS), comprising the brain and spinal cord, has been considered for a long time as "a forbidden city", in which the immune system is denied entry as its activity is perceived as a possible threat to the complex and dynamic nerve cell networks. Furthermore, immune cells that recognize the brain's own components ("autoimmune" cells) are viewed as a real danger as they can induce autoimmune diseases. Thus, although autoimmune cells are often detected in the healthy individual, their presence there was perceived as an outcome of the body's failure to eliminate them.  But Schwartz’s group showed that these autoimmune cells have the potential ability – if their levels are controlled – to fight off debilitating degenerative conditions that can afflict the CNS, such as Alzheimer’s and Parkinson's diseases, glaucoma, amyotrophic lateral sclerosis (ALS), and the nerve degeneration that results from trauma or stroke.

 

In their earlier research, Schwartz and her team provided evidence to suggest that T cells directed against CNS components do not attack the brain but instead, recruit the help of the brain's own resident immune cells to safely fight off any outflow of toxic substances from damaged nerve tissues.

 

In the present study, the scientists showed that the same immune cells may also be key players in the body's maintenance of the normal healthy brain. Their findings led them to suspect that the primary role of the immune system's T cells (which recognize brain proteins) is to enable the "neurogenic" brain regions (such as the hippocampus) to form new nerve cells, thus maintaining the individual's capacity for learning and memory. The work is an outcome of a long-time collaborative effort of Prof. Schwartz and Dr. Jonathan Kipnis (a former student and post-doctoral fellow in Schwartz’s lab and now assistant professor in Nebraska) together with graduate students Yaniv Ziv, Noga Ron and Oleg Butovsky, and in collaboration with Dr. Hagit Cohen of the Ben-Gurion University of the Negev, Beer Sheva. 

 

It was reported before that rats kept in an environment rich with mental stimulations and opportunities for physical activity exhibit increased formation of new nerve cells in the hippocampus. In the present work, the scientists showed for the first time that formation of these new nerve cells following environmental enrichment is linked to local immune activity. To find out whether T cells play a role in this process they repeated the experiment using mice with severe combined immune deficiency (scid mice), which lack T cells and other important immune cells. Significantly fewer new cells were formed in those mice. On repeating the same experiment, this time with mice possessing all of the important immune cells except for T cells, they again found impairment of brain-cell renewal, confirming that the missing T cells were an essential requirement for neurogenesis. They observed that the specific T cells that are helping the formation of new neurons are the ones recognizing CNS proteins.

 

To substantiate their observations, the scientists injected T cells into immune-deficient mice with the objective of replenishing their immune systems. The results: cell renewal in the injected mice was partially restored – a finding that supported their theory.

 

In another set of experiments, they found that mice possessing the relevant CNS-specific T cells performed better in some memory tasks than mice lacking CNS-specific T cells. Based on these findings, the scientists suggest that the presence of CNS-specific T cells in mice plays a role in maintaining learning and memory abilities in adulthood.

 

Schwartz points out that the role of the autoimmune T cells is not to affect the level of intelligence or motivation, but rather, to allow the organism to achieve the full potential of its brainpower. "These findings," she says, "give a new meaning to 'a healthy mind in a healthy body'. They show that we rely on our immune system to maintain brain functionality, and so they open up exciting new prospects for the treatment of cognitive loss." Knowledge that the immune system contributes to nerve cell renewal has potential far-reaching implications for elderly populations, because aging is known to be associated with a decrease in immune system function. It is also accompanied by a decrease in new brain cell formation, as well as in memory skills. Therefore, by manipulating and boosting the immune system, it might be possible to prevent or at least slow down age-related loss of memory and learning abilities.

 

Prof.  Michal Schwartz’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Alan T. Brown Foundation to Cure Paralysis; the Carl and Micaela Einhorn-Dominic Institute for Brain Research; Mr. and Mrs. Irwin Green, Boca Raton, FL; and  Mr. and Mrs. Richard D. Siegal, New York, NY.  Prof. Schwartz is the incumbent of the Maurice and Ilse Katz Professorial Chair of Neuroimmunology.

Life Sciences
English
  • Michal Schwartz
  • T cell›T cells in the CNS

In the Loop

English

A Weizmann Institute study finds that signals travel from a rat’s whiskers to its brain along three separate pathways

 

Like blind peoples’ fingers, rats use their whiskers to engage in active sensing – a combination of movement and touch – when trying to figure out the location and identity of a certain object. But how the brain decodes the signals it receives from the whiskers is unclear.
 
Ph.D. student Chunxiu Yu, working together with colleagues Dori Derdikman and Dr. Sebastian Haidarliu in the laboratory of Prof. Ehud Ahissar of the Weizmann Institute's Neurobiology Department, have now provided surprising new insights into the mechanisms involved, suggesting that the signals travel from the whiskers through three distinct regions in the thalamus – a central gateway of the brain – along three separate pathways: One conveying signals relating to whisker movement; the second conveying touch signals (providing information on where an object is); and the third conveying complex combinations of movement and touch signals (providing information on what the object is). They propose that these pathways function within three parallel feedback loops that control various aspects of sensor movements much like thermostats controlling temperature – by constantly monitoring the signals they receive and changing their responses accordingly.
  
The authors suggest that these separate pathways work in parallel on different levels of a brain hierarchy, with the higher, more complex levels (object identification) building on the lower levels (movement and touch) to implement new behaviors.

 

Prof. Ehud Ahissar’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Carl and Micaela Einhorn-Dominic Institute for Brain Research; the Edith C. Blum Foundation; the Irving B. Harris Foundation; and Ms. Esther Smidof, Switzerland. Prof. Ahissar is the incumbent of the Helen Diller Family Professorial Chair in Neurobiology.


The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.


Weizmann Institute news releases are posted on the World Wide Web at
http://wis-wander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/.

Life Sciences
English
  • Ehud Ahissar
  • Neural pathway
  • Whiskers

Weizmann Institute Scientists Devise an Approach For 'Recruiting' an Immune System Response to Partial Spinal Cord Injuries

English

Severing the spinal cord causes complete paralysis of the organs innervated by the central nervous system, from the point of injury downwards. In fact, even a partial injury of the spinal cord may cause complete paralysis. The main reason for this is that damaged fibers create a 'hostile environment' which harms other, undamaged fibers. As a result, even in cases of partial spinal cord injury, the damage continues to spread, intensifying the paralysis. Blocking the spread of damage may therefore save the nerve cells undamaged by the initial trauma, and with them - at least some of the patient's motor activity. This is what the Weizmann Institute scientists hope to achieve.

 

Damage Control

Several years ago, a team of researchers led by Prof. Michal Schwartz of the Weizmann Institute's Neurobiology Department found that following neuronal injury, immune cells known as macrophages may be 'recruited' to encourage repair and renewed growth of damaged nerve fibers.

 

Profs. Schwartz and Irun R. Cohen of the Immunology Department now hope to take this research one step further. They propose adding additional immune cells, known as T-cells, to the damage-control battalion aimed at blocking the spread of spinal cord damage.

 

At first glance, this idea seems to oppose the widespread view of immune cells as potentially damaging to the central nervous system (brain and spinal cord). However, this revolutionary treatment has already been successfully tested on laboratory animals, as described by the researchers in their article appearing in the current issue of the medical journal The Lancet.

 

Seek Out and Destroy

T-cells function to prevent infection by seeking out and destroying pathogenic 'enemies' that infiltrate the body. But the body may also possess T-cells that are directed against its own components. The accepted notion is that such anti-self T-cells are harmful factors that may cause autoimmune diseases, such as multiple sclerosis and diabetes. However, the Institute scientists have now shown that a controlled amount of these autoimmune cells, when directed against specific neuronal components, can assist in curbing injury-induced neuronal damage.

 

Following treatment with anti-self T-cells, rats with partial injuries of the spinal cord regained some motor activity in their previously paralyzed legs, while untreated rats developed increasing paralysis, and sometimes even total paralysis. These findings may lead to an innovative clinical treatment for preventing total paralysis after partial spinal cord injury. This treatment will be based on extracting immune cells from the patient's blood, increasing their amount, and then re-introducing them into the damaged neuronal area. 'The concept is to work together with the body's existing self repair mechanism, which apparently requires encouragement and monitoring,' explains Prof. Michal Schwartz.

 

The scientists participating in this study were Ehud Hauben, Uri Nevo, Eti Yoles, Gila Moalem, and Eugenia Agranov, in collaboration with Prof. Michal Neeman from the Weizmann Institute and Prof. Solang Akselrod from Tel Aviv University.

 

The study was funded by Proneuron Ltd.

 

Prof. Michal Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology. Prof. Irun Cohen holds the Helen and Morris Mauerberger Chair in Immunology.

 

The Weizmann Institute of Science is a major scientific research graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science.

Life Sciences
English
  • Immunology
  • Macrophage
  • Michal Schwartz
  • Spin›Spinal cord injury
  • T cell

Functional MRI Will Enable Non-Invasive Visualization of brain Cortical Columns

English

The issue of the scientific journal Nature Neuroscience (24.1.00) includes two articles describing scientific findings based on functional MRI (fMRI) and optical imaging technology, that may considerably advance the field of brain research as well treatment of neurological disorders. The accomplishment is the result of parallel research efforts made by scientists from Minnesota University USA, and the Weizmann Institute of Science.


Brain researchers throughout the world aspire to accurately map nerve cell clusters in action --'conversing' with their peers in the form of electrical impulses, while processing sensory information or performing cognitive functions.

Each cluster, containing thousands of nerve cells performing a given processing task, is called a 'cortical column.' Cortical columns are the 'microprocessors' of the brain. Brain researchers maintain that the ability to obtain an exact mapping of the cortical column is critical to understanding how the human brain can perform its remarkable functions. Yet, until now they have been unable to do so directly, and have had to rely on several indirect methods such as Positron-Emission-Tomography (PET), optical imaging and fMRI.
 

Brain-Vein Mapping

These methods are based on the more than 100 years old discovery made by Lord Sherrington of a connection between the brain's electrical activity and changes in blood circulation. For example, PET is based on injecting a radioactive substance into the blood stream and mapping the locational alterations in blood flow in response to electrical activity in the brain. Using fMRI, scientists track changes in the levels of oxygen bound to hemoglobin in the blood stream, resulting from hemoglobin supplying oxygen to active nerve cells. fMRI is entirely non-invasive, hence its advantage over PET, which relies on the injection of radioactive tracers. Therefore, fMRI may be used to explore the same brain for many years, thereby potentially enabling researchers to track and map memory traces, aging processes, or functional recovery from trauma or stroke.


Until recently, the level of mapping accuracy rendered by these techniques was fairly limited: they could map an active area in the human brain at an accuracy level of 1-3mm (fMRI) or 3-7mm (PET), and thus were unable to map the brain's basic processing units - the 0.5mm wide 'microprocessors.'

Mapping Brain microprocessors

In the last 15 years, Prof. Amiram Grinvald of the Weizmann Institute's Neurobiology Department has developed a novel optical imaging brain-mapping approach based on tracking color changes in the blood supplying oxygen to the active microprocessors. Using this technology, Grinvald was able to identify the exact time and place in which nerve cells consume oxygen from the blood-dense microcirculation system. The high resolution achieved by optical imaging permitted him to fully map individual cortical columns - the brain's 'microprocessors.' These included visual system microprocessors related to shape, color, and motion perception. Optical imaging also laid the foundation for the development of functional MRI, which is more suitable for non-invasive human brain research and clinical applications. Initially, scientists hoped that using fMRI would enable brain mapping at the same level of accuracy achieved by the optical imaging technology. Indeed, both methods detect a considerable 'activity crest' that appears roughly 6 seconds after the onset of electrical activity. Unfortunately, the fMRI systems could not detect the 'initial dip,' a negative signal that appearsearlier, which is clearly visible by optical imaging systems.

'Initial Dips' and 'Activity Crests'

This is where things stood until recently. Two months ago, however, Ivo Vanzetta and Amiram Grinvald of the Weizmann Institute of Science, published a paper in Science in which they proposed how the fMRI system's resolution could be greatly enhanced. A team of scientists from Minnesota University, led by Prof. Kamil Ugurbil, has adopted this 'recipe.' First, they found the missing 'initial dip' with fMRI, thus showing that the two techniques can monitor the same vascular events provided the fMRI is done in a strong magnetic field. (Just like with optical imaging, the 'initial dip' provides a much smaller signal relative to the delayed 'activity crest.' Therefore, naturally, fMRI researchers had previously used the greater 'activity crest' to map the exact location of electrical activity.)


However, Dae-Shik Kim, Timothy Duong, and Seong-Gi Kim from the Minnesota group report today in Nature Neuroscience that this 'activity crest' cannot be used to monitor the precise location of electrical activity with fMRI. The major finding of their report is that the exact location of 'firing' indeed corresponds to the location of the 'initial dip.' Utilization of this small signal enabled the first exact mapping of 'orientation columns' -- the microprocessors responsible for shape perception in early processing areas of the visual cortex.


The current Nature Neuroscience contains a News and Views article written by Amiram Grinvald, Hamutal Slovin and Ivo Vanzetta of the Weizmann Institute, in which they discuss the accomplishment achieved by the Minnesota team, and provide new data from optical imaging. Taken together, these articles suggest that by focusing on the 'initial dip,' fMRI will enable non-invasive mapping of cortical columns in human brain research as well.


Scientists believe that the pivotal improvement in MRI accuracy will greatly advance scientific research aimed at better understanding the fundamental mechanisms underlying human perception and higher cognitive functions. Additionally, it may have valuable significance in improving the capacity for early diagnosis and perhaps prevention of diverse mental disorders.


Prof. Grinvald, who holds the Helen and Norman Asher Professorial Chair in Brain Research, is head of the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions and of the Wolfson Center for Applied Scientific Research in Functional Brain Imaging at the Weizmann Institute.
This study was supported by the German Israeli Foundation for Scientific Research and Development, the Horace W. Goldsmith Foundation, of New York and Ms. Margaret Enoch of New York.


The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science
 
 
Life Sciences
English
  • Amiram Grinvald
  • Brain
  • Nerve cell
  • Optical imaging
  • fMRI

New Understanding Of A Key Control Mechanism In The Brain

English


Despite more than a century of research on inhibitory neurons, very little is known on how this small population (10-20% of brain neurons) exerts its controlling effect on the brain. Pivotal for normal brain development, learning, and memory, it is not surprising that inhibitory neurons are involved in most neurological disorders. A recent study at the Weizmann Institute, published in the January 2000 issue of Science, reveals key principles underlying the design and function of this inhibitory system.


By repressing the level of activity in neighboring neurons, inhibitory neurons (I-neurons) prevent the brain from quickly spinning out of control into hyper-excited states or full-blown epilepsy. One of the problems that children with autism and attention deficit hyperactivity disorders (ADHD) have is I-neuron malfunction: their inhibitory system does not effectively suppress unwanted information, impeding their ability to make choices. I-neuron malfunction is involved in memory disorders (such as Alzheimer's disease), neural trauma, and addictions. It also plays a role in a wide range of psychiatric disorders, such as depression, obsessive compulsive disorders, and schizophrenia.


In the past, researchers basically thought that I-neurons just sprayed an inhibitory neurotransmitter called GABA onto their neighbors. But this did not explain how they inhibited the right neurons at exactly the right time and to the right degree. The new study carried out in the laboratory of Prof. Henry Markram of the Weizmann Institute's Neurobiology Department shows how they achieve this.


Controlling the Neuron Crowd

The research team found new types of I-neurons, revealing that this tiny population is several times more diverse than previously thought. Further, using new methods that they developed, the researchers succeeded in recording directly how individual inhibitory neurons control their neighbors. They found that I-neurons build complex synapses (connections) onto their target neurons. The synapses selectively filter inhibitory messages, enabling I-neurons to shut down the activity in neighbors as required. These synapses act as fast-switching 'if-then' filtering gates that allow inhibition to be applied only at the exact millisecond and to the right degree.


Each I-neuron establishes complex if-then gates onto thousands of neighboring neurons and is therefore 'in charge' of controlling their activity. The gates allow I-neurons to rapidly switch their focus onto any one neuron that they are connected to. This ingenious design principle is what enables the small group of I-neurons to exert such a sophisticated effect, simultaneously 'giving personal attention' to the activity of each of the neurons to which they are connected.


At the Negotiating Table

The researchers showed that a 'discussion' between I-neurons and target neurons is involved in deciding which type of if-then gate should be set up to filter the inhibitory message. This decision-making process could allow each neuron in the brain to be inhibited in a potentially unique way. Dubbed the 'interaction principle', this process generates maximal diversity of if-then gates, allowing more complex and finer control over large numbers of neurons.


A Potential Brain-Mapping Tool

The researchers went on to reveal a remarkable ability of I-neurons: they can sense neurons that share the same functions in the brain. I-neurons 'select' groups of target neurons to construct the same type of if-then gates, possibly enabling the I-neurons to control groups of neurons collectively. It also means that I-neurons can 'smell-out' neurons in the brain that collaborate in the most elementary functions even if they seem different in almost every other way (i.e., they can identify neurons descended from the same 'ancestors').


'I-neurons can trace family trees of neurons. In other words, they could help us to work out how neurons are related to each other. This could one day enable us to map the functional aspect of the brain according to the genealogy of neurons - an organizing principle that we never dreamt possible,' says Markram. The researchers believe that the ability to detect functionally related groups in the brain, called 'the homogeneity principle,' results from common signal molecules released by target cells. I-neurons may use the signal molecules to determine what kind of if-then gates to build. Future research designed to identify the nature of these molecules could yield a potent tool for mapping the functional structure of the brain.


This research was funded by the Human Frontier Science Program Organization, the Israel Ministry of Science, the Israel Science Foundation, the US Navy, Minna James Heineman Stiftung, the Abramson Family Foundation and the Nella and Leon Benoziyo Center for Neurosciences.


The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.

Life Sciences
English
  • Brain
  • Henry Markram
  • Neuron

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