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Thread: Study Zeroes in on Spine's Walking Control Center

  1. #1
    Senior Member Jeremy's Avatar
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    Study Zeroes in on Spine's Walking Control Center

    Study Zeroes in on Spine's Walking Control Center

    Fri Mar 21, 7:49 AM ET Add Health - Reuters to My Yahoo!



    NEW YORK (Reuters Health) - New research into what makes some mice hop like a bunny reveals a bit more about how the spinal cord controls normal movements.

    A better understanding of the spinal cord's role in controlling movement, researchers say, could eventually lead to new treatments for people whose legs are paralyzed.


    Scientists have known that mice that are genetically engineered to lack one of two related spinal-cord molecules do not move as other mice do. Instead of moving one hind leg and then the other, these altered mice move both legs at once, making them hop rather than scurry.


    But how these missing molecules cause mice to hop has been uncertain.


    Now researchers in Europe have identified the neurons in the spinal cord that seem to make mice hop. These neurons are located within spinal-cord networks called central pattern generators.


    A report on the research appears in the March 21st issue of the journal Science. Dr. Klas Kullander of Gothenburg University and AstraZeneca Transgenics and Comparative Genomics in Sweden led the study.


    Normally, the activity of neurons on each side of the spinal cord is balanced. Neurons that encourage movement are balanced out by neurons that inhibit it. This balance leads to smooth movements in normal mice, with the muscles in the right hind leg contracting as the muscles in the left leg relax.


    But in the mutant mice, the neurons Kullander's team identified upset the balance in the spinal cord's central pattern generators. The signal to move overwhelms the signal to rest, which causes both legs to move at once rather than to alternate.


    The researchers were able to use chemicals to restore the balance in the spinal cord, which resulted in normal movements.


    The neurons identified in the study make up just a part of the system that controls movement, but learning more about this system could lead to new treatments for people whose legs are paralyzed, according to Kullander and his colleagues.


    Eventually, they speculate, it may be possible to improve their movements by stimulating the spinal cord circuits that are involved in walking.

  2. #2
    Kangaroo mouse reveals walking metronome

    Molecules behind left-right generator might help spinal cord treatments.
    21 March 2003
    HELEN PEARSON

    Nerves in the spinal cord form a circuit that controls walking.
    テつゥ GettyImages

    Thanks to a mouse that jumps like a kangaroo, researchers have discovered two molecules that drive the ability to walk. They hope that similar results might eventually help people to recover from spinal-cord injuries.

    Many animals' spinal cords house a circuit called the central pattern generator (CPG), which triggers legs to perform a left-right gait. Some therapies for partially paralysed patients attempt to stimulate the CPG by supporting them over a treadmill and sending electrical pulses to the spine.

    But exactly which nerves are involved, and how they work, has been unclear. For Klas Kullander, of Gothenburg University in Sweden, and his colleagues, the clue came from mice genetically engineered to lack two molecules called ephrinB3 and EphA4.

    These molecules it seems, help growing nerves to wire up the CPG correctly. In the mutant animals, nerves that normally hook up to only one side of the spinal cord stray into both1. Electrical signals shoot from both sides of the fork, triggering the legs to kangaroo-kick.

    Michael O'Donovan, who studies spinal cord circuits at the National Institutes for Health in Bethesda, Maryland, is upbeat about the new results. When exploring the CPG, "the main limitation up until now was knowing the molecules involved", he says.

    EphrinB3 and EphA4 are unlikely to make therapies because they are most important when the spine is growing in the embryo. But "if we found a molecule unique to the CPG, that might be a target [for therapy]", says O'Donovan.

    Once researchers have better characterized the CPG's nerves and how they are controlled, they might also find drugs that stimulate them. But any treatment of this kind remains some way in the future, warns spinal-cord researcher Serge Rossignol of the University of Montreal, Canada. "It's always a long shot," he says.

    Rhythm section

    The CPG is intriguing. It drives rhythmic movement without the help of the brain; hence headless chickens can briefly sprint around the yard before keeling over. But, in humans at least, "it's rather an elusive concept", says O'Donovan.

    Brain signals are thought to direct the speed, pace and direction of walking. So although babies can kick, they must still to learn to walk by co-ordinating this ability with balance and movement. The CPG also seems to benefit from feedback signals from the moving legs - this may by why treadmill training helps those with injuries.


    References
    1. Kullander, K. et al. Role of Eph4 and EphrinB3 in loncal neuronal circuits that control walking. Science, 299, 1889 - 1892, (2003). |Homepage|

    http://www.nature.com/nsu/030317/030317-12.html

  3. #3
    Author Topic: テつ* Back and forth with Eph and EphrinNeurons controlling alternating limb movements require a receptor-ligand pair.

    Max

    Member posted Mar 21, 2003 03:57 PM テつ*
    ------------------------------------------------------------------------
    Back and forth with Eph and EphrinNeurons controlling alternating limb movements require a receptor-ligand pair. | By Richard Robinson



    The rhythmic, alternating movements of locomotion have a sizeable local spinal control element, and can be generated even in the absence of stimulus from the brain, but how these patterns are organized and controlled on a cellular level has been unclear. In the March 21 Science, Klas Kullander and colleagues at Gothenburg University, Sweden, show that neurons bearing the EphA4 receptor play a pivotal role, and that the absence of either EphA4 or its ligand disrupts normal locomotor development and activity (Science, 299:1889-1892, March 21, 2003).

    Kullander et al. examined neurophysiologic activity in isolated spinal cords from mice null for EphA4 or its ligand, ephrinB3. Opposing ventral nerve roots displayed synchronous activity in both mouse types, versus alternating activity in wild-type mice, giving rise to a rabbit-like gait pattern. Heterozygotes displayed a mixed or drifting pattern. In mice homozygous null for either gene, neurons whose growth was normally restricted to one side of the spinal cord grew across the midline to make contact on the other side. Normal locomotion could be restored by application of an inhibitory neurotransmitter, indicating Eph4A synapses play an excitatory role in central locomotor pattern generation.

    The authors emphasize that further understanding of the molecular basis of normal locomotion "is essential in the ongoing effort to reestablish locomotor function in patients with spinal cord injury."

    Links for this article
    O Kjテδヲrulff et al., "Distribution of networks generating and coordinating locomotor activity in the neonatal rat spinal cord in vitro: A lesion study," Journal of Neuroscience, 16:5777-5794, 1996.
    http://www.jneurosci.org/cgi/content/full/16/18/5777

    K Kullander et al., "Role of EphA4 and EphrinB3 in local neuronal circuits that control walking," Science, 299:1889-1892, March 21, 2003.
    http://www.sciencemag.org

    Gothenburg University
    http://www.gu.se/



    http://www.biomedcentral.com/news/20030321/01/
    ------------------------------------------------------------------------
    Posts: 4443テつ*|テつ*From: Montreal,Province of Quebec, CANADAテつ*|テつ*Registered: 07-25-01

  4. #4
    Senior Member Max's Avatar
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    Kangaroo mouse reveals walking metronome

    Kangaroo mouse reveals walking metronome
    Molecules behind left-right generator might help spinal cord treatments.
    21 March 2003
    HELEN PEARSON


    Nerves in the spinal cord form a circuit that controls walking.
    テつゥ GettyImages



    Thanks to a mouse that jumps like a kangaroo, researchers have discovered two molecules that drive the ability to walk. They hope that similar results might eventually help people to recover from spinal-cord injuries.

    Many animals' spinal cords house a circuit called the central pattern generator (CPG), which triggers legs to perform a left-right gait. Some therapies for partially paralysed patients attempt to stimulate the CPG by supporting them over a treadmill and sending electrical pulses to the spine.

    But exactly which nerves are involved, and how they work, has been unclear. For Klas Kullander, of Gothenburg University in Sweden, and his colleagues, the clue came from mice genetically engineered to lack two molecules called ephrinB3 and EphA4.

    These molecules it seems, help growing nerves to wire up the CPG correctly. In the mutant animals, nerves that normally hook up to only one side of the spinal cord stray into both1. Electrical signals shoot from both sides of the fork, triggering the legs to kangaroo-kick.

    Michael O'Donovan, who studies spinal cord circuits at the National Institutes for Health in Bethesda, Maryland, is upbeat about the new results. When exploring the CPG, "the main limitation up until now was knowing the molecules involved", he says.

    EphrinB3 and EphA4 are unlikely to make therapies because they are most important when the spine is growing in the embryo. But "if we found a molecule unique to the CPG, that might be a target [for therapy]", says O'Donovan.

    Once researchers have better characterized the CPG's nerves and how they are controlled, they might also find drugs that stimulate them. But any treatment of this kind remains some way in the future, warns spinal-cord researcher Serge Rossignol of the University of Montreal, Canada. "It's always a long shot," he says.

    Rhythm section

    The CPG is intriguing. It drives rhythmic movement without the help of the brain; hence headless chickens can briefly sprint around the yard before keeling over. But, in humans at least, "it's rather an elusive concept", says O'Donovan.

    Brain signals are thought to direct the speed, pace and direction of walking. So although babies can kick, they must still to learn to walk by co-ordinating this ability with balance and movement. The CPG also seems to benefit from feedback signals from the moving legs - this may by why treadmill training helps those with injuries.


    References
    Kullander, K. et al. Role of Eph4 and EphrinB3 in loncal neuronal circuits that control walking. Science, 299, 1889 - 1892, (2003). |Homepage|


    テつゥ Nature News Service / Macmillan Magazines Ltd 2003

    http://www.nature.com/nsu/030317/030317-12.html

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