Behind Closed Eyes

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Weizmann Institute research shows our brain's sense centers are continuously active. In the absence of a stimulus, however, their electrical activity remains in 'screen saver' mode

 

Even when our eyes are closed, the visual centers in our brain are humming with activity. Weizmann Institute scientists and others have shown in the last few years that the magnitude of sense-related activity in a brain that’s disengaged from seeing, touching, etc., is quite similar to that of one exposed to a stimulus. New research at the Institute has now revealed details of that activity, explaining why, even though our sense centers are working, we don’t experience sights or sounds when there’s nothing coming in through our sensory organs.

 

The previous studies of Prof. Rafael Malach and research student Yuval Nir of the Neurobiology Department used functional magnetic resonance imaging (fMRI) to measure brain activity in active and resting states. But fMRI is an indirect measurement of brain activity; it can’t catch the nuances of the pulses of electricity that characterize neuron activity.

 

Together with Prof. Itzhak Fried of the University of California at Los Angeles and a team at the EEG unit of the Tel Aviv Sourasky Medical Center, the researchers found a unique source of direct measurement of electrical activity in the brain: data collected from epilepsy patients who underwent extensive testing, including measurement of neuronal pulses in various parts of their brain, in the course of diagnosis and treatment.

 

An analysis of this data showed conclusively that electrical activity does, indeed, take place even in the absence of stimuli. But the nature of the electrical activity differs if a person is experiencing a sensory event or undergoing its absence. In results that appeared recently in Nature Neuroscience, the scientists showed that during rest, brain activity consists of extremely slow fluctuations, as opposed to the short, quick bursts that typify a response associated with a sensory percept. This difference appears to be the reason we don’t experience hallucinations or hear voices that aren’t there during rest. The resting oscillations appear to be strongest when we sense nothing at all – during dream-free sleep.

 

The slow fluctuation pattern can be compared to a computer screen-saver. Though its function is still unclear, the researchers have a number of hypotheses. One possibility is that neurons, like certain philosophers, must ‘think’ in order to be. Survival, therefore, is dependant on a constant state of activity. Another suggestion is that the minimal level of activity enables a quick start when a stimulus eventually presents itself, something like a getaway car with the engine running. Nir: ‘In the old approach, the senses are ‘turned on’ by the switch of an outside stimulus. This is giving way to a new paradigm in which the brain is constantly active, and stimuli change and shape that activity.’

 

Malach: ‘The use of clinical data enabled us to solve a riddle of basic science in a way that would have been impossible with conventional methods. These findings could, in the future, become the basis of advanced diagnostic techniques.’ Such techniques might not necessarily require the cooperation of the patient, allowing them to be used, for instance on people in a coma or on young children.  

 

Prof. Rafael Malach’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; Ms. Vera Benedek, Israel; Benjamin and Seema Pulier Charitable Foundation, Inc.; and Ms. Mary Helen Rowen, New York, NY. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.


For the scientific paper, please see:  http://www.nature.com/neuro/journal/v11/n9/full/nn.2177.html


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.
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The Ins And Outs Of Acetylcholine

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A team of scientists from the Weizmann Institute and France's Centre National de la Recherche Scientifique (CNRS) has recently shown that the acetylcholine neurotransmitter plays a double role in learning and memory.

While prior studies had already demonstrated that adding acetlycholine to neuronal junctions during learning affects information reception and storage, subsequent testing of the cell's ability to retrieve the information produced inconsistent results. The findings ranged from significant or slight improvement following acetylcholine application, to the lack of any learning enhancement whatsoever.

In recent years, scientists throughout the world have tried to elucidate the reasons underlying these varying results. Now, a team of researchers headed by Drs. Ehud Ahissar of the Weizmann Institute's Department of Neurobiology and Daniel Shulz of the U.N.I.C. laboratory at the CNRS, have shown how acetylcholine is able to consistently enhance neuronal learning and information retrieval.

The secret, researchers found, is to control the level of acetylcholine at the neuronal junctions during both the 'ins' and 'outs' of information processing - specifically, during information reception and storage, as well as during its retrieval and implementation.

These findings, due to appear in the February 3rd issue of Nature, represent yet another step in unraveling the enigma of learning and memory embodied within the brain, as well as probing the causes of cognitive deficits observed in patients with Alzheimer's and other neurodegenerative diseases.

This research was funded by the Abramson Family Foundation, USA.


The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
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Innovative Treatment Enables Paralyzed Rats to Regain Partial Use of Their Hind Legs

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REHOVOT, Israel -- June 30, 1998 -- Weizmann Institute scientists have managed to partially heal the damaged spinal cords of laboratory animals, according to a study reported in the July issue of Nature Medicine. A team led by Prof. Michal Schwartz of the Neurobiology Department used an innovative treatment which allowed rats to regain partial movement in their hind legs that had been paralyzed by damage to the spine.

"The results of our experiments are promising," says Prof. Schwartz. "However, for the moment they have only been achieved in rats, and much additional research still needs to be done before the new treatment is available to humans."

It has long been known that "lower" animals, such as fish, can repair damaged fibers in the central nervous system -- the spinal cord and the brain -- and restore lost function. In contrast, mammals, including humans, can only repair injuries to the peripheral nerves, while injuries to the brain or spine leave them permanently paralyzed or otherwise handicapped.

The new approach is based on Schwartz's theory which states that the loss of this repair ability occurred in the course of evolution due to a unique relationship between the central nervous and the immune systems. More specifically, Schwartz believes this loss was probably dictated by the need to protect the mammalian brain from the effects of the immune system: While immune cells normally help to heal damaged tissue, their access to the brain would disrupt the complex and dynamic neuronal networks that build up during an individual's lifetime.

Generally, when tissue damage occurs, immune cells known as macrophages swarm to the injured site where they remove damaged cells and release substances that promote healing. The central nervous system of mammals is different in this regard: when damaged, it is not effectively assisted by the immune system.

Schwartz's team discovered that this is because the mammalian central nervous system has a mechanism that suppresses the macrophages. As a result, macrophages are recruited to central nervous system injuries at a lower rate, and those that are recruited fail to become optimally "activated" and effective.

These findings led to a series of experiments with rats in the course of which the researchers managed to overcome the limited ability of the damaged central nervous system to recruit and activate the macrophages. They isolated macrophages and incubated them in a test tube in the presence of a damaged peripheral nerve. The macrophages, which received the distress signals of the damaged peripheral nerve, became activated.

At this stage, the researchers returned the activated macrophages to the damaged site in the central nervous system of the paralyzed rat. The transplanted macrophages created a growth-inducing environment around the damaged tissue. As a result of the treatment, the rats were able to regain partial motor activity in their previously paralyzed legs. They were able to move their hind legs and several animals were even able to place their weight upon them.

A major innovative aspect of such treatment lies in promoting the animal's own self-repair mechanism. In fact, the new treatment offers the option of using the animal's own cells for this purpose.

Further research is necessary to see if this approach will work in "higher" animals, such as humans.

Yeda Research & Development Co. Ltd., the Weizmann Institute's technology transfer arm, has submitted patent applications for the new treatment. In order to promote this research and develop it further for possible clinical use, Yeda has entered into a licensing agreement with Proneuron Biotechnology Ltd., a start-up company located in the Kiryat Weizmann Industrial Park, adjacent to the Institute.

Prof. Schwartz holds the Maurice and Ilse Katz Chair of Neuroimmunology.
 
 
The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot,    Israel.
Life Sciences
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Personnel Management in the Brain

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The brain acts like a dynamic personnel manager, constantly shifting its "workers," the nerve cells that control nearly all bodily functions, from one cell group to another to deal with a variety of ever-changing demands, according to a Weizmann Institute study published this month in Advances in Processing and Pattern Analysis of Biological Signals.

The study disproves the prevailing notion that nerve cells, or neurons, in the brain either act on their own or form permanent working groups. Instead, neurons were shown to belong to a number of different groups and to change their momentary affiliation in accordance with the task to be performed, thus coordinating the processes involved in seeing, hearing and movement control.

Using a groundbreaking technique that makes it possible to record the electrical activity of many individual neurons at the same time, Prof. Ad Aertsen of the Neurobiology Department and colleagues at the Hebrew University of Jerusalem have shown that two neurons may closely communicate with each other when processing one type of signal, but completely ignore each other when responding to another kind.

If these findings are corroborated, they will have implications for such fields as neurology, where it is vital to know how a task carried out by one set of neurons may affect the function of other brain cells, and computer science, branches of which deal with simultaneous processing of information flowing along multiple paths.



Prof. Aertsen collaborated with Prof. Eilon Vaadia of the Hebrew University-Hadassah Medical School and the Center for Neural Computation, the Hebrew University of Jerusalem.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel.
Life Sciences
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Keeping the Memories Alive

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Are our memories recorded in a one-time physical change, like writing permanently on a clay tablet? Prof. Yadin Dudai, Head of the Weizmann Institute's Neurobiology Department, and his colleagues recently discovered that the process of storing long-term memories is highly dynamic, sustained by a molecular machine that must run constantly. They showed that stopping the machine even briefly can erase some types of long-term memories. These findings, which appeared recently in Science, may pave the way to future treatments for memory problems.
 
Dudai and research student Reut Shema, together with Todd Sacktor of the SUNY Downstate Medical Center, trained rats to avoid certain tastes. They then injected a drug to block a specific protein into the taste cortex – an area of the brain associated with taste memory. They believe that this protein acts as a miniature "machine" that keeps memory running by actively maintaining physical, learning-induced changes in the synapses – the conduits for signals between nerves. The scientists reasoned that blocking the protein would reverse those changes. Regardless of the taste the rats were trained to avoid, they forgot their learned aversion after a single application of the drug into the brain, and the signs so far indicate that the unpleasant memories of the taste had indeed disappeared. This is the first time that memories were shown to be susceptible to erasure long after their formation.
 
"This drug is a molecular version of jamming the operation of the machine," says Dudai. "When the machine stops, the memories stop." These findings raise the possibility of developing future, drug-based approaches for boosting and stabilizing memory.
 
Prof. Yadin Dudai's research is supported by the Norman and Helen Asher Center for Brain Imaging; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer's Research Fund; and the Sylvia and Martin Snow Charitable Foundation. Prof. Dudai is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.
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A Rose by Any Other Name

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A rose is a rose is a rose; but do we, the artist and the poet all see the same flower in the same way?

This age-old philosophical question has now been put to the test by scientists at the Weizmann Institute.

While no one can actually “get inside” the head of another, for neurobiologists, modern biological imaging methods such as fMRI are the next best thing. The f stands for “functional,” meaning that the magnetic images record changes in the brain’s blood flow while it is in the process of thinking or experiencing, responding to stimuli or performing set tasks, allowing scientists to accurately pinpoint the areas involved in each function.

To compare individual perceptions of visual experiences, Prof. Rafael Malach and Uri Hasson, along with their colleagues in the Neurobiology Department, showed volunteers a segment of a movie (in this case, the classic Western The Good, the Bad and the Ugly) while they were undergoing brain scans with fMRI.

The scans allowed the scientists to see which areas of the subjects’ brains were active during love scenes or gunfights. Because a movie offers a wealth of different visual stimuli - scenery, faces, action, etc. - the researchers were able to track the brains’ response to a rich, dynamic scene. A change in experimental stimuli turned up surprising results. Rather than showing the subjects carefully selected slides or photos - the typical visual stimuli used in such experiments - the researchers showed them a movie. Essentially, rather than presenting one type of stimulus and then looking for the response, the brain areas themselves were allowed to select their own fare from a smorgasbord of possibilities, and the scientists then took note of the brain’s selections.

What they found was a striking similarity between brain activity patterns in all the subjects; so much so that the patterns of one brain could be used to predict activity in other brains when viewing the same segment. “Despite our strong sense of individuality, such a high level of agreement among subjects implies that our brains ‘tick together’ when exposed to the same visual environment,” says Malach.


Interestingly however, the brain scans also revealed that within an individual brain, different regions are active in viewing different parts of the movie. Because each area is activated by a specific kind of visual cue, it only picks up on those bits that “speak” directly to its specialized preference. For instance, a region known to be involved with face recognition lights up only when close-ups appear on the screen, while scenery elicits a response from another part of the brain that helps us navigate in three-dimensional space. The scientists noted a third area that seemed to be activated when actors performed delicate hand motions. They believe this last area may be part of a network of brain regions used to understand the actions and intentions of others. “While you perceive a single, whole movie, different regions of your brain are each processing a private motion picture of their own,” says Malach. “The unified percept you experience is, in fact, the result of a tremendous ‘jam session’ played by many different, highly specialized brain areas.”

Watching brain patterns

Prof. Malach’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions; the Norman and Helen Asher Center for Brain Imaging; the Edith C. Blum Foundation Inc.; the Mary Ralph Designated Philanthropic Fund and the James S. McDonnell Foundation.

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