Re: Fwd: Memories are made of these

From: Scott Chase (
Date: Fri Mar 08 2002 - 20:05:30 GMT

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    From: "Scott Chase" <>
    Subject: Re: Fwd: Memories are made of these
    Date: Fri, 08 Mar 2002 15:05:30 -0500
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    >From: "Wade T.Smith" <>
    >To: "memetics list" <>
    >Subject: Fwd: Memories are made of these
    >Date: Fri, 8 Mar 2002 09:00:52 -0500
    >Memories are made of these
    >by Damaris Christensen, BioMedNet News
    >7 March 2002 16:30 EST
    >Elegant research released today from Nobelist Eric Kandel's laboratory
    >reveals that the cAMP response element binding protein (CREB), long
    >implicated in memory consolidation, primes brain cells to retain
    >long-term memories. Regulated expression of CREB, during or shortly
    >before a memory task, might allow single-trial learning, and eventually
    >lead to development of memory-enhancing drugs, Kandel says.
    >In general, nerve cells become more tightly linked when stimulated by a
    >series of high-frequency electrical pulses, says Kandel, professor of
    >physiology at Columbia University. This increase in synaptic strength -
    >known as long-term potentiation, or LTP - may last for hours, days or
    >even weeks, and is critical in learning and memory formation.
    >Kandel and his colleagues engineered mice to express a chimeric CREB
    >protein with an acidic transactivation domain from HSV-VP16, sensitive to
    >the antibiotic doxycycline. Compared to neurons from wild-type mice,
    >neurons in the engineered mice need a smaller first stimulus to generate
    >a lasting increase in synaptic strength, Kandel says.
    >"You need to store information, and information storage may require new
    >building blocks," said John Lisman, professor of biology at Brandeis
    >University. "This is one more step in showing that CREB has the power to
    >provide these building blocks for a local process of synaptic
    >CREB is thought to activate a number of genes that act in concert to
    >produce synaptic changes associated with LTP. "Overexpressing CREB primes
    >all of the synapses so that if you just weakly kiss any of those synapses
    >you can capture a response to that signal," Kandel explained.
    >In wild-type mice, a single 100 Hz tetanus train - a series of quickly
    >repeated electric pulses - lasting for 1 second, produces a
    >non-saturating, short-lasting LTP. In mice overexpressing CREB, the same
    >tetanic train evoked an enhanced LTP lasting at least 3 hours. The
    >results are published today in Cell.
    >Feeding the VP16-CREB mice with doxycyline, which turns off expression of
    >the chimeric VP16-CREB, for 2-3 weeks reversed the effects, so the mice
    >responded normally to tetanic stimulation, Kandel reports.
    >The transgenic CREB did not affect basal synaptic activity, although it
    >did upregulate a number of genes activated by CREB, Kandel says. "Our
    >data indicate that CRE-mediated transcription is one of the prerequisites
    >for the consolidation of long-term synaptic changes," said Kandel.
    >Specifically, he adds, VP16-CREB activity can lead to cell-wide priming
    >for LTP by seeding the synaptic terminals with proteins and mRNAs
    >required for the stabilization and capture of long-term LTP.
    >That can be good and bad, Kandel says. Preliminary tests of behavior in
    >the engineered mice suggest they have trouble remembering navigational
    >cues. That's because once a nerve cell is primed to respond to one
    >signal, it can't unlearn the signal through depotentiation, and the brain
    >simply overloads.
    >Kandel and his team are now testing whether they can using doxycycline to
    >turn the VP16-CREB on and off so that the mice can be primed to remember
    >certain tasks very well without chronic boosting of LTP. If so, Kandel
    >says, it suggests that it may eventually be possible to design drugs to
    >briefly boost a person's memory.
    Hey Dace, you listening?

    There's also the NMDA receptor thingy amongst other angles related to LTP.
    Something to do with Hebbian synaptic plasticity changes.

    I've been reading William Calvin's take on the Hebbian cell assembly in his
    book _The Cerebral Code_. Those nifty though speculative hexagonal thingies
    sound like the possible basis for engrammatic (or mnemonic) competition for
    limited cortical space.

    Oh, and Dace, wouldn't forgetting kinda resemble deletion of a file from a
    disk as a matter of managing information? Sometimes even people type out a
    word processing document and print it without committing it to the storage
    space of a disk.

    Brain damage from heavy drugs might be analogous to leaving a disk on one's
    dashboard in the hot sun.

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