Flies offer clues to anesthesia-resistant memory

A fruit fly gene called radish, and the newly identified protein it encodes, have opened doors to understanding the genes and neuronal networks that govern a special type of memory, termed anesthesia-resistant memory. Researchers had previously known that for most animals — not just humans — loss of consciousness from anesthesia causes amnesia for recently experienced events. In contrast, for reasons that are not well understood, older memories are resistant to the effects of anesthesia. With the help of model organisms such as Drosophila, different types of memory are also now beginning to be identified on the basis of genetic requirements. This week, new analysis of a fly gene required for anesthesia-resistant memory sheds light on the nature of this memory type, and what makes it different from other kinds of stable memories.

The new work, reported by Josh Dubnau and colleagues at Cold Spring Harbor Laboratory in New York, was based on some well established observations regarding learning and memory in the fruit fly. In Drosophila, memory of an odor-electric shock association is at first easily erased by anesthesia-induced loss of consciousness. Within the first hour after this memory forms, however, it becomes more resistant to anesthesia. For over a decade, memory researchers have known that this form of memory, anesthesia-resistant memory, does not form in a mutant strain of flies bearing a mutation in the gene called radish. Until now, however, the molecular basis for the radish memory defect has been a mystery.

Dubnau and colleagues have now identified the radish gene, and shown that it encodes a protein known as a phospholipase-A2, an enzyme that cleaves phospho-lipids on the cell membrane to release a chemical called arachidonic acid (AA). While the mechanism of action of AA in stabilizing memory still is unknown, this molecule has already been implicated in memory formation in chickens and rodents. The current genetic findings from flies therefore suggest that the radish/phospholipase A2-dependent form of memory spans distantly related animal phyla. The authors also traced expression of the radish gene in the fly brain, leading them to identify a network of neurons that had not been previously known to function in memory. The new insights into radish gene function provide geneticists with a valuable foothold to investigate the cellular mechanisms of anesthesia-resistant memory.

Ann-Shyn Chiang, Allison Blum, Jody Barditch, Ying-Hsiu Chen, Shu-Ling Chiu, Michael Regulski, J. Douglas Armstrong, Tim Tully, and Josh Dubnau: “radish Encodes a Phospholipase-A2 and Defines a Neural Circuit Involved in Anesthesia-Resistant Memory”

Published in Current Biology, Volume 14, Number 4 February 17, 2004, pages 263-272.