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Proteins linked to synaptic 'memory.'

Proteins linked to synaptic 'memory'

Several investigators have noted that when individual neurons are given brief but intense bursts of high-frequency electrical stimulation, their electrical properties change and chemical transmissions across their connecting synapses increase for hours or days. This process, known as long-term potentiation and readily demonstrated in cells from a small brain structure called the hippocampus, may play a crucial role in the formation of memories.

Stanford University School of Medicine researchers report that the protein kinases -- several related substances involved in the regulation of chemical messengers and their receptors in neurons -- are key to the chemical mechanisms underlying long-term potentiation.

Physiologist Roberto Malinow and his colleagues used two protein-kinase-inhibiting substances to study long-term potentiation in rat hippocampus cells. When either of the two substances -- sphingosine or a synthetic compound called H7 -- is applied to hippocampal synapses shortly before high-frequency stimulation, long-term potentiation is blocked, the investigators note in the Oct. 27 NATURE.

But sphingosine, which subdues the activity of two protein kinases, does not dampen the increased electrical charge associated with long-term potentiation when applied immediately after the stimulation. In contrast, H7 -- which interferes with the activity of additional protein kinases -- inhibits long-term potentiation even after high-frequency stimulation clearly establishes the effect. Surprisingly, the researchers add, when H7 degrades after several hours, there is an almost complete recovery of the original long-term potentiation.

The results indicate a "sphingosine-sensitive process" is critical to induce long-term potentiation, the researchers suggest, whereas an unidentified protein kinase affected by H7 is crucial for its maintenance.

Unfortunately, writes biologist Mary B. Kennedy of the California Institute of Technology in Pasadena in an accompanying comment, both sphingosine and H7 are insufficiently specific to distinguish among the several known protein kinases. Even if the critical protein kinases are pinned down, says Kennedy, much remains to be explained about long-term potentiation. There are now indications that one class of postsynaptic receptors involved in this process releases a chemical messenger able to travel back and forth across the synapse.

"Other entirely new messenger systems may be awaiting discovery," Kennedy concludes.
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Author:Bower, Bruce
Publication:Science News
Date:Nov 5, 1988
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