Fwd: Toggling nature's auto-erase

From: Wade T.Smith (wade_smith@harvard.edu)
Date: Wed Mar 14 2001 - 03:10:01 GMT

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    Toggling nature's auto-erase

    Mice tests show how gene controls a memory feature

    By Richard Saltus, Globe Staff, 3/9/2001

    http://www.boston.com/dailyglobe2/068/nation/Toggling_nature_s_auto_eraseP.
    shtml

    orgetting too much can be bad, but remembering too much can also be a
    handicap.

    Evolution equipped the brains of animals with an automatic-erase feature
    that prevents a torrent of trivial events from clogging long-term memory.

    Now, scientists have shown they can switch this device off and on in
    mice. When it is disabled, the mice perform feats of superior learning
    and memory. Switched back on, the rodents become pedestrian learners
    again.

    Dr. Eric R. Kandel, a Nobel laureate neuroscientist at Columbia
    University, headed a team that's reporting the memory advance in today's
    issue of the journal Cell.

    ''I think this is one of a number of steps toward finding targets in the
    brain'' for future drugs to improve or restore memory, Kandel said in an
    interview.

    Larry Squire, a memory researcher at the University of California in San
    Diego, agreed but cautioned that tinkering with nature's balance of
    memory and forgetting could be risky.

    ''It's been said that a better memory isn't necessarily an optimal
    memory; you can remember too much,'' Squire said in a telephone
    interview. ''But if you have people with failing memories, that's a
    different story.''

    Kandel, whose coauthors included Gael Malleret at Columbia and Isabelle
    M. Mansuy of the Swiss Federal Institute of Technology, said the brain is
    regulated by molecular switches that can make memories easier or harder
    to form. Memories are processed for storage in a part of the brain called
    the hippocampus.

    A molecule called calcineurin is the key player in the balance of brain
    chemicals that determines whether a thought vanishes instantly or gets
    encoded as a long-term memory. The more active calcineurin is, the harder
    it is for the hippocampus to store a thought. When calcineurin is less
    active, thoughts become memories more easily.

    Kandel's team bred mice with a foreign gene that could be turned on and
    off by giving the rodents a common antibiotic, doxycycline. The gene made
    calcineurin more or less active.

    Then they compared the performance of those mice and normal mice on
    standard memory tests. In one set of tests, the mice were shown a novel
    object, and the mice, by their behavior, indicated how long they
    remembered it was new to them.

    In another set of tests, mice had to learn and remember how to swim to a
    submerged, hidden platform that allowed them to stand safely in a water
    bath.

    When mice were given doxycycline and their calcineurin was turned down by
    the gene switch, they learned faster and remembered longer, said the
    report. For as long as a week after the experiment, the mice that
    received the drug remembered the object was new. But by two weeks, the
    memory had faded.

    Then the scientists ended the dosage of doxycycline, which allowed
    calineurin to be more active and memories harder to form. Given the same
    test, the mouse no longer had superior memories.

    ''I would call this a real but modest enhancement of memory,'' said
    Kandel. The genetic switching didn't improve extremely long-term memory,
    and it didn't affect so-called working memory, holding two or three
    things in mind while performing a task.

    Kandel next wants to test the system on aging mice, to determine whether
    blocking calcineurin will prevent the erosion of memory with age.

    This story ran on page 4 of the Boston Globe on 3/9/2001. © Copyright
    2001 Globe Newspaper Company.

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