Principles of Psychobiology©
Interactive Study Guide for the Allied Neurosciences

Visit the Principles of Psychobiology home page for details about our innovative software for students in the brain sciences.

Link to this Page (HTML code, Instructions, etc.)
Tell a Friend about this site
Test Your "Brainpower"
Brain Models, charts, study-guides, and more...

Recommended books

Clues about Phantom Pain -- Functional Plasticity in the Somatosensory System

    Researchers at the University of Toronto and The Toronto Hospital have discovered a biological basis for the phantom sensations that are frequently experienced on the missing limbs of amputees. The findings of the study were published in the Jan. 22 issue of Nature.  The researchers found that the neurons in the brain that used to represent sensation in the lost limb were still functional but now driven by the stimulation of other body parts, usually the part of the body closest to the amputated limb. The investigators also found that in patients experiencing phantom pain, the sensation can be recreated by stimulating within the brain. Phantom sensations could not be elicited, however, in amputees without a history of phantom sensations.
    "Many amputees have a sense of their missing limb and frequently these sensations are painful," says investigator Andres Lozano, an associate professor in the department of surgery at U of T and a neurosurgeon at TTH. "Phantom pain can severely compromise the quality of life of patients who have already had to adjust to a change in body image and quite often their activities of daily living."
    The thalamus functions as a relay centre in the brain, receiving messages from the the somatosensory system of the skin (input) and sending these impulses to higher centres in the neocortex (output) (Module 7: Principles of Psychobiology).  In human the somatosensory neocortex interprets where and how the sensation is perceived. "Amputation can change the representation of the body surface in the brain, but until now it has been unclear how these changes relate to phantom sensation," says Professor Jonathan Dostrovsky of the department of physiology at U of T, who was also involved in conducting the study.
    The team of scientists and clinicians at the U of T and TTH treating people experiencing chronic pain and movement disorders through the electrical stimulation of the thalamus identified an opportunity to investigate phantom sensations. They hypothesized that in amputees who experience phantom sensations, the area in the thalamus originally representing the missing limb remains functional and stimulating this area of the thalamus results in phantom sensations.
    The study involved six amputees in the pain/movement management program who all had chronic pain following amputation; four had experienced phantom pain and two people experienced pain in their stump but had not experienced phantom sensations. As part of their treatment for chronic pain, the patients underwent surgery to map the sensory areas in the brain. During the mapping process the investigators were able to stimulate the patients' thalamus and the patients were able to report what they felt because they were conscious, enabling the researchers to learn about sensory output from the thalamus.
    "In addition to providing patients and caregivers with a sense of reassurance knowing that there is a biological basis for phantom pain, the research has helped us understand the ability of neurons to adapt to change, a characteristic referred to as plasticity," says
Karen Davis, an assistant professor in the department of surgery at U of T and neurophysiologist at TTH who, along with Dostrovsky and U of T postdoctoral physiology fellow Lei Luo, were the basic scientists involved in the study. "Although the results won't immediately change how we treat phantom sensations, we can now study a larger group of patients and try to further understand the plasticity of neurons."
    Some amputees develop pain in their phantom or stump and this is frequently very difficult to control with conventional
therapies. Continuous electrical stimulation through electrodes surgically implanted into the thalamus has been found to provide relief of this pain in some patients. "This technique blocks spontaneous neuronal activity in the thalamus that is thought to cause phantom sensations,"explains Lozano who notes the bursting' activity of neurons may be responsible for spontaneous phantom pain, an hypothesis the investigators plan to pursue.
 

Recommended books

Brain Antibodies Provide Clues to Tourette's Syndrome

    Tourette's syndrome affects approximately five in every 10,000 persons.  Tourette's syndrome affects the inhibitory control of voluntary motor function, and patients oftentimes exhibit "tics" and inappropriate vocalizations.  Because it occurs with high frequency in some families and identical twins, a genetic error has long been suspected as a cause. "However, based on family studies, it appears that for some individuals, an additional factor is required to cause the disease," says says Harvey Singer, M.D., professor of neurology and pediatrics at Johns Hopkins, and lead author a study published in the June 1998 issue of Neurology.
    One hypothesis is that people who have two copies of the Tourette's gene always develop the syndrome, while those who receive one copy of the gene, estimated at about 2 percent of the general population, develop Tourette's only after being exposed to another factor in the environment, such as an infection. The Tourette's gene has not yet been isolated.
     "We think antibodies made by the immune system in response to a bacterial infection may go on to attack brain nerve cells in a subset of the children who develop Tourette's," . "The bacteria streptococcus is a leading suspect, but the search for a triggering factor should not be limited to it."
    With funding from the National Institutes of Health and the Tourette's Syndrome Association, Singer's group took blood samples
from 41 Tourette's patients and a group of 39 control subjects, and tested them for antibodies to proteins in ground-up human brain tissue. The patients had significantly higher levels of antibodies against proteins from the putamen, an area at the base of the brain involved in movement.  For two other brain areas studied, the caudate and the globus pallidus, there were no significant differences between patients and controls.
    "(Previous) Brain imaging studies have shown changes in the shape and size of the putamen in Tourette's patients, reinforcing the idea that these antibodies may contribute to the disorder," says Singer. Strep infection is a leading suspect for the trigger in a small number of patients because scientists have already linked it to another, similar disorder, Sydenham's chorea, and patients have reported cases in which Tourette's began or became worse after a streptococcal infection.

Recommended books

Recovery of Function Might Be Speeded By Direct Electrical Stimulation Of The Brain

    Neurons exhibit the ability to modify both their synaptic connections and their synaptic efficiency.  Such plasticity underlies the ability of the brain to process information and produce motor responses, and it contributes to our ability to recognize, discriminate, and remember stimuli. It is also known that neural plasticity contributes to recovery of function after brain damage, such as that which occurs following stroke.
    Stroke patients often regain a substantial amount of the brain function lost after brain cells die. Exercises to regain control over movements or to recover the ability to speak or to understand language, for example, often lead to significant recovery of function. However, for psychological and neurological reasons, stroke patients often lack the motivation to participate vigorously in rehabilitation programs. And, because brain resources are usually more limited after a stroke, it is often difficult for a patient to voluntarily and reliably produce normal movements or speech.
    If all sensory input was processed equally in the brain, we would probably not learn successfully to adapt and respond to our surroundings. During learning, many brain structures "filter" and "enhance" incoming information to help weigh the importance of stimuli.  Current hypotheses also suggest that certain responses in neurons are "potentiated" during learning so that neurotransmitter released during learning will cause both short- and long-term changes in synaptic connections and efficiency (Module 5: Principles of Psychobiology).  Presumably, these change in brain activity during learning affect certain brain regions, such as the neocortex, that function to further process stimuli during learning.
    It is known that one brain region, the nucleus basalis, is especially important in learning and other cognitive functions. Nucleus basalis has recently been considered in this role because it is known that cells containing the excitatory  are located in nucleus basalis (Module 6: Principles of Psychobiology), axons of nucleus basalis neurons project widely to the neocortex, and cells in the nucleus basalis degenerate during Alzheimer's disease, which produces sensory, motor, and memory disorders.
    Michael Merzenich, Ph.D., Professor of Otolaryngology at UCSF, and graduate student Michael Kilgard reported in the March 13, 1998 issue of Science that the auditory neocortex undergoes a greater degree of plasticity as a function of direct electrical stimulation of nucleus basalis.
    Although the brain normally "focuses" attention to stimuli that are being learned, direct electrical stimulation of the nucleus basalis may bypass this requirement, according to Merzenich.   "Just as direct electrical stimulation in the basal ganglia now is used as a treatment for Parkinson's disease, stimulation of the nucleus basalis to coincide with an important-to-remember stimulus or movement might serve as a means to overcome motivational problems in the early epoch of stroke recovery," Merzenich says. "In essence, this strategy could quickly maximize the full potential for recovery of function in a damaged brain," he adds.  "Our strategy has been to trick the brain into sending a message that says 'save this.'
    To explore and map out in detail the learning-related changes in the auditory cortex, Kilgard exposed normal rats to sounds of assorted frequencies and bandwidths, about 300 times a day for 20 days. The experimental group of 21 rats received auditory stimuli coinciding with mild electrical stimulation of the nucleus basalis. Another group received the auditory stimuli but no electrical stimulation. In the electrically stimulated rats, the auditory cortex became dramatically rearranged to respond to the specific frequencies that were used as sound stimuli. The researchers recorded no changes in rats that were not electrically stimulated.
     It is known that the topographical maps of the sensory neocortices in humans and other mammalian species are determined by both genetic factors, and the history of the organism's sensory stimulation. "The extent of reorganization in the auditory cortex generated by activating the nucleus basalis is substantially larger than the reorganization that is typically observed after several months of intensive behavioral training," according to Merzenich.  Thus, it appears likely that nucleus basalis may be one brain region that contributes the brains ability to engage in synaptic plasticity.

Recommended books

Fetal Cell Therapy Benefits Some Parkinson's Patients
Source:  NIH-National Institute Of Neurological Disorders And Stroke

    Results from the first randomized, controlled clinical trial of fetal dopamine cell implants for Parkinson's disease show that the surgery helped a small number of Parkinson's patients, but not all who underwent the experimental therapy. These results raise important questions in the search for improved treatments for Parkinson's disease. The study,led by Curt Freed, M.D., at the University of Colorado in Denver, and Stanley Fahn, M.D., at Columbia-Presbyterian Medical Center in New York, included 40 patients with advanced Parkinson's disease. Half the patients received the cell implants, while half had a placebo surgery which appeared very similar to the implant procedure. The results will be announced at the 51st annual meeting of the American Academy of Neurology in Toronto. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS).
    The 40 patients in this study were randomly selected to receive either the cell therapy or the placebo. Patients in the implant group received injections of dopamine-producing cells into the putamen, the area of the brain in which progressive loss of dopamine production triggers the symptoms of Parkinson's disease. Patients given the placebo surgery received four small cosmetic holes in the skull that looked like those made for the implant therapy but which did not penetrate the brain or its tough protective membrane, called the dura. All patients were informed of the risks of the surgery and the possibility that they might initially be in the non-therapeutic placebo group. The patients were evaluated periodically for 1 year after the procedure before they learned whether or not they had received the cell implant therapy. Those originally in the placebo group were then given the opportunity to receive the cell transplants.
    After 1 year, the treated patients under age 60 (9 of the total patients in the trial) showed significant improvements in movement. Patients over age 60 who received the implants, as well as those who had the placebo surgery, showed no significant improvements in any of their symptoms. On another important measure, the study showed that patients did not perceive a benefit from the therapy in terms of their normal daily activities.
    "Any gains against this terrible, common disorder are welcome," said Gerald Fischbach, M.D., Director of NINDS. "We are proud to be the sponsors of this trial. Although not all measured outcomes were positive, there was clear improvement in control of movement in Parkinson's patients 60 years of age or younger. There is reason to be encouraged."
 PET brain scans showed that more than half of the patients who received the implants had a greater than 20 percent increase in dopamine activity in the putamen, regardless of age. There were no significant surgical complications during this clinical trial, confirming that both the implant and the placebo surgery are safe when performed by an experienced surgeon. While there were significantly more severe adverse experiences during the 1-year follow-up period in patients who received the implants than in those who received placebo, these severe adverse experiences showed no consistent or logical pattern that could be associated with the surgery or the implant. "Further studies must clarify adverse reactions which are seemingly unrelated but cannot be ignored," said Dr. Fischbach.
    Previous studies of fetal dopamine cells for Parkinson's disease in the 1980s and 1990s showed what sometimes appeared to be remarkable benefits. Dopamine is a nerve-signalling chemical, or neurotransmitter, that influences many parts of the brain, including those that control movement. Publicity surrounding these early clinical trial results led to great patient demand for cell implant therapy. Until now, however, researchers could not be certain whether the effects seen in these earlier clinical trials were due to the therapy or to psychological factors.
 The 5-year, $5.7 million trial was the first clinical study of fetal tissue implants to receive federal research funding after a ban on funding of this type of research was lifted in 1993. The current Congressional prohibition on use of federal funds for human embryo research extends only to studies in which a human embryo is created for research purposes or is subjected to risks greater than those allowed for fetuses in utero.
    In addition to Dr. Freed and his colleague Robert Breeze, M.D., at the University of Colorado, the research team included Dr. Fahn and colleagues at Columbia-Presbyterian Medical Center, who performed all clinical evaluations of the patients, and David Eidelberg, M.D., and colleagues at North Shore University Hospital -- Cornell University Medical College, Long Island, who performed the PET brain scans to detect any changes in dopamine activity. This collaboration helped ensure that neither the researchers who evaluated the patients nor the patients themselves knew who had received the treatment or the placebo.
    While the study results indicate that fetal cell implants can help some patients younger than age 60, they also raise important questions, including why the treatment did not benefit older patients. Furthermore, the implants did not reduce the need for any drugs that patients in the study were taking for Parkinson's disease. The next steps will be to determine whether the benefits last over time, whether other therapies are more beneficial, and whether there might be different forms of Parkinson's disease depending on the age of the patient. More analysis of the results from this trial and additional years of patient follow-up are needed to answer these questions.

Recommended books

More on Neurological Substrates of Dyslexia

    Researchers have presented additional neurological evidence that the region of the brain that processes brief, rapidly successive sounds is functionally abnormal in adults with the reading disability known as dyslexia. The findings, documented through simultaneous brain imaging and behavioral tests, indicate that adult dyslexics have an enduring neurological deficit in their ability to process these brief, rapidly successive sounds.  They suspect that the deficiency contributes to difficulties in early speech and language learning, which may lead to a weakness in the ability to learn to read.
    The study was published in the May 24 issue of Proceedings of the National Academy of Science.  Perhaps the most provocative aspect of the finding, the researchers said, is the clear and direct neurological evidence that reading deficits are generated, at least in part, by a deficit at a very fundamental level of cortical processing of sound inputs.
    "Our findings indicate that there is a basic problem in signal reception, as complex sound information streams into the cerebral cortical system underlying aural speech representation," said the senior author of the study, Michael Merzenich, PhD, the Francis A. Sooy Professor of Otolaryngology and a member of the Keck Center for Integrative Neuroscience at UC San Francisco. "The way that the brain processes sound in poor readers is very different from its processing and representation of rapidly changing sound inputs in competent readers."
    "Our research indicates that adult dyslexics are representing the sound parts of words by the activation of cortical neuron populations in a weaker and less salient form within their cortical aural speech processing system. We believe that they, therefore, are not delivering the normal forms of representation of the separable sound parts of words to the regions of the brain involved in speech perception and reading," he said.  The authors emphasize that their findings do not discount the additional involvement of other brain regions in dyslexia, where more complex combinations of information lead to the recognition and interpretation of speech.
    At the same time, they argue that the very elementary defect in the brain's processing of sound must be playing an important role in the generation of relatively weak neuronal representations of the sound parts of aural speech. And this elementary neurological deficit, they said, could provide a target for remedial therapies aimed at training the brain to increase the speed and accuracy with which it processes rapidly successive and rapidly changing sounds.
    The sound-processing function occurs at a base, or entry, level of sound processing in the brain, and is believed to be a primary step in the brain's representation of normal speech sounds and its creation of speech and language-reception abilities. The process ultimately culminates with a listener learning to recognize the sound parts of words, and to translate these word sounds as written letters.
    Previous behavioral studies have suggested that the inability to parse the rapidly successive, changing sounds that make up words, the phonemes of language, may be the primary basis of language-learning impairments in children. Scientists have long argued that children who have difficulty parsing word sounds are destined to have difficulty successfully initiating reading.  Other behavioral studies have indicated that most people with dyslexia, characterized by a difficulty with reading, also have impairments in the fidelity of their auditory reception. However, because most dyslexics ultimately develop facile speech reception and production capabilities, the significance of this problem for the origin of reading impairments has been unclear.
    The researchers conducted their current study in seven dyslexic adults who were of normal intelligence but severely challenged by reading, spelling and writing. Results were compared with those recorded in seven adults of normal intelligence who were competent readers.  The dyslexic adults performed poorly on standardized reading tests. And, as has been shown to be the case with the great majority of adult dyslexics, these poor readers (ages 18-42) also performed poorly on a variety of tests that measured their ability to discern rapidly successive sound stimuli.
    In one of these sound-discerning tests, adults were exposed to two sounds that differed in frequency and that occurred a tenth or a fifth of a second apart. They were then asked to identify the sounds and to replay the sequence in which they were presented. Their brain activity was simultaneously recorded using magnetoencephalographic brain imaging, which measures magnetic field fluctuations generated by spatially localizable human brain activity with millisecond precision.
    In these studies, the UCSF team focused on the activity generated by the rapidly successive sounds evoked from the primary auditory cortical areas, where information about aural speech flows into the cerebral cortex's processing system for language. Poor readers did report hearing the two very brief sounds, and often knew that in some way they weren't the same, but they were unable to identify them, or to reliably reconstruct the sequence in which they were represented.
    "The reason," said Srikantan Nagarajan, PhD, an assistant adjunct professor of otolaryngology and a member of the Keck Center for Integrative Neuroscience at UCSF, and the lead scientist of the study, "was demonstrated by the abnormal way that the brain of the poor-reading subjects responded to these rapidly successive sound events."
    "In normal readers, the auditory cortex generated clear, separate representations of sounds occurring within the time dimensions of a syllable," said Nagarajan. "In poor readers, the brain separately generated only very weak representations of sound events past the first sound.  "In the normal reader, successive intra-syllabic sound events are separately represented in high fidelity within the processing channels of the 'primary' auditory cortex. In the impaired reader, they are not," he said.
    "These findings are consistent with the increasing evidence," said Merzenich, "that language-impaired and reading-impaired children are a very broadly synonymous population. Scientists have historically argued that only a small percentage of dyslexics have a clear history of early language impairment and fundamental auditory processing deficits. To the contrary, we have seen that most poor readers and most language-impaired children share these same fundamental listening and brain processing abnormalities."  Moreover, he said, "The studies show that these fundamental listening problems clearly persist across a lifetime, even while the basic speech reception abilities of these individuals can ultimately achieve a relatively normal competency."

Recommended books

More on Cellular Differences in Depression

    Scientists at the University of Mississippi Medical Center have provided further evidence that two types of brain cells are abnormal in the brains of people who suffer from clinical depression and most of whom committed suicide.
Dr. Grazyna Rajkowska, associate professor of psychiatry and human behavior, looked at the region of the brain known as the prefrontal cortex. This "gray matter" -- located just behind the forehead -- is responsible for higher intellectual functions and regulation of emotional and motivational behavior.  The results of Rajkowska's work appear in the lead article in the May issue of the journal, Biological Psychiatry.
    Earlier work that scanned the same region of the brain in living subjects indicated that this region of the brain was smaller in those who suffered from depression than in the brains of those who did not.  "The decrease in volume was an indication to me that something was unusual in the cell architecture and that there might be cellular changes in that area," she said.
    The changes Rajkowska noted were in neurons and glial cells. The neurons are the basic unit of the brain, transmitting and receiving signals and processing information. Glial cells form the "support system" for the neurons. They don't transmit impulses, but they control the nutrients the neurons get from the blood, are active in the immune response and generally facilitate the work of the neurons. While other scientists pinpointed changes in glial cells in one region of the cerebral cortex in individuals with depression, Rajkowska's work at the same time found changes in both types of cells in three different regions of the cerebral cortex.
    Rajkowska's career has been spent examining changes in the brain in several types of psychiatric and neurological illnesses including schizophrenia, manic-depressive illness and Huntington's disease. Her current research in depression showed there are fewer glial cells in the brains of people with depression and that the neurons in the same brains were smaller than normal and lower in density. The opposite is true in neurodegenerative diseases such as Huntington?s chorea. "In these kinds of brain illnesses, neurons die, and the glial cells try to compensate and support the neurons that are still alive. That's why there are more glial cells in diseases classified as neurodegenerative," Rajkowska said.
    Further studies will show whether the changes in the brain were the result of depression or anti-depressant medication prescribed to help depression.
    To sort out that information, Rajkowska will work with neuroendocrinolgist Dr. Garth Bissette, professor of psychiatry at UMC, who has an animal model for depression in rats and will look at rats given antidepressants and those not given medication.  "If the structural changes we're seeing do, in fact, coincide with clinical depression, we could be looking at a major step toward designing better antidepressants," she said. "We will certainly know more about the mechanisms of depression."
    Rajkowska's work also points to depression as more than a "chemical imbalance," as it's been called. "It's actually a complicated physiological illness that involves both brain structure and biological processes," she said.  Rajkowska uses brain tissue collected by Dr. Craig Stockmeier of the University Hospitals of Cleveland and Case Western Reserve University in Cleveland, Ohio. There, researchers seek permission from the families of suicide victims for donation of brain tissue and an interview. By asking certain key questions, the interviewer determines if the person who committed suicide also had major depression or another type of psychiatric illness. In addition, donations of brain tissue are sought from people who had no history psychiatric illness.
    "These control subjects are valuable standards for comparison with the suicide victims," Stockmeier said. "They enable us to identify abnormalities in the brains of people with clinical depression." 

Recommended books

Molecules That Guide Nerve Cells During Development

     When nerve cells migrate from their birthplace to their permanent home in the brain, how do they find  their way? Researchers have discovered the first molecular guide, a known protein called Slit. This protein doesn't attract young cells to where they need to go. It repels them, like a dog herding a flock of sheep.
  "This is the first demonstration of a diffusible molecule that directs migrating neurons," says Yi Rao, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "Such a repulsive molecule might be useful for controlling the unwanted migration of tumor cells or for delivering therapeutic cells to specific regions of the brain in patients with Parkinson?s disease or Alzheimers?"
   Rao and Jane Y. Wu, M.B., Ph.D., assistant professor of pediatrics and of molecular biology and pharmacology, directed the research. Visiting research technician Wei Wu, from the Chinese Academy of Sciences in Shanghai, was first author of the paper, which appears in the July 22 issue of Nature.
   "This finding has important conceptual implications," says Pasko Rakic, M.D., Ph.D., professor and chair of neurobiology at Yale University School of Medicine. "Although it previously has been suggested that some brain structures may release factors that repulse neurons, Rao and his colleagues are the first to identify specific genes whose products perform this function."
  In the early 1970s, Rakic obtained the first definitive electron microscopic evidence of neuronal migration and proposed that interactions among different types of cells help direct it. In the past decade, he and others have identified several families of genes and molecules that recognize the "highways" for cell  movement. "The novelty of the finding by the St. Louis group is that their molecules are diffusible and are distributed as  concentration gradients that migrating cells can read," Rakic says.
  Scientists realized in 1888 that brain cells might migrate. Now it is known that the majority travel, even after birth. In humans, for example, young neurons continue their migration to the cerebellum-- the part of the brain that controls movement -- during the first two months of life.
  Nerve cell migration can't be studied directly in humans, so the researchers worked with rats. They looked at the olfactory bulb, which gives rodents their all-important sense of smell. During the first two weeks of life, this structure continues to enlarge as a cell nursery in the brain, the subventricular zone, sends it nerve cell precursors. The subventricular zone and the olfactory bulb are several millimeters apart, so the young neurons have to travel several thousand times their length to reach their target. But until now, the molecular signposts have remained obscure.
   During the course of a different study, Rao and Wu became interested in Slit, which is secreted by cells in the midline of the embryo. Since 1996, they have cloned slit genes from several  different animals. They also showed that two of the three slit genes are active in the midline of the rat septum. This part of the forebrain was known produce a substance that repels migrating neurons. Studying brain tissue from rats 4 days to 7 days of age, the researchers placed pieces of subventricular zone into gel. This enabled them to observe the neurons that flocked away from the tissue in all directions. But when they also added a piece of septum to the gel, the migration pattern changed as the majority of the migrating cells traveled away from the direction of the septum.
  To determine whether this repulsive activity was due to Slit or some other substance from the septum, the researchers cultured pieces of subventricular zone with kidney cells, which normally don't make Slit. The young neurons migrated in a symmetrical pattern.  But when they used kidney cells that had been genetically altered to make Slit, the neurons migrated in the opposite direction.
  The researchers then placed a piece of subventricular zone midway between two masses of Slit-producing kidney cells. The young neurons migrated symmetrically. But when one mass was farther away than the other, the neurons migrated away from the closest mass. So it appears that a concentration gradient rather  than a certain amount of Slit guides the migration of young neurons.
  The researchers then studied Slit's effect on neurons in their natural surroundings. Wei Wu isolated sections of forebrain that  contained the subventricular zone, the olfactory bulb and the  pathway between them - the RMS (rostral migratory stream). By  labeling the neuronal precursors with dye, the researchers were  able to see them migrating in the RMS. But when they placed  Slit-producing kidney cells on the RMS, very few young neurons  ventured forth. "This experiment provides strong evidence that  Slit can repulse neurons in their natural setting," Jane Wu says.
  In the intact rat brain, the subventricular zone lies around the septum. "So neurons run away from it anteriorly into the olfactory  bulb, their final destination," says Rao.
  In four papers in the March 19 issue of Cell, the Washington University researchers and scientists in California reported that  Slit interacts with a cell-surface protein called Roundabout  (Robo). This receptor is made by certain neurons in the olfactory  bulb. In the present study, the Washington University researchers  engineered mammalian cells that produced and secreted RoboN,  the extracellular fragment of Robo. Then they used the RoboN to  prevent Slit from interacting with the normal Robo receptor.
  They placed pieces of septum on top of the kidney cells and  cultured them with pieces of subventricular zone. When they used  normal kidney cells, the septum repelled migrating neurons. But  when they used the kidney cells that made RoboN, the septum had  much less effect on neuronal migration. "Again, this suggests that  Slit is the substance in the septum that repels migrating neurons,"  Jane Wu says.
  The four papers in Cell revealed that Slit guides the growth of  axons, the long cables that extend from nerve cell bodies toward  other nerve cells. It functions as a repellent, preventing axons  from crossing the body's midline. Now the Washington University  researchers have shown that Slit guides the migration of the cell  bodies themselves, it appears that the same protein enables nerve  cells to reach their correct locations and to link up with each  other as they settle in. "There have been two schools of thought,"  Rao says. "One is that projecting axons and migrating neurons are  quite different. The other is that there are similarities between  them. Our study supports the latter."
  Axon guidance involves molecules that attract axons as well as  repulsive molecules. "You can have a mother who is encouraging  you to do something or a mother who makes you insecure and  drives you away," Rao says. "For neuronal migration, we have  found a molecule acting like a mother that drives you away."
  The discovery of a repulsive guidance molecule suggests a  possible strategy for treating neurodegenerative diseases. "If you  wanted to transplant neurons, you might not be able to inject them  into the right part of the brain without damaging other cells," says  Rao. "But perhaps you could inject them into a less vulnerable  part of the brain and use Slit to drive them to the intended region."

Recommended books

What's the Critical Period for Language Acquisition?

Scientists have new insights into how and when language develops. NPR presents the extraordinary case of a British child, who had half his brain removed at age eight because of a rare disease, that acquired speech very rapidly at the age of nine.  This observation suggests the window for learning language is open years longer than previously believed.

More on this development from National Public Radio...
Click Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)

Recommended books

Was Einstein's Brain Different?

Structure-function relationships have been tested for over a century, particularly in attempts to identify possible localization of function.  Perhaps the most intriguing analysis is that of Einstein's brain.  Functionally, we know that Einstein was able to propose and solve some of the most perplexing scientific problems that have ever existed for the human mind.  But, was his brain any different from the rest of us?  NPR discusses observations relating to Einstein' brain.

More on this development from National Public Radio...
Click Here For NPR© Link (REAL AUDIO (tm) INTERVIEW)