Sci. Aging Knowl. Environ., 10 December 2003
Vol. 2003, Issue 49, p. nw168
[DOI: 10.1126/sageke.2003.49.nw168]


What's That Smell?

Aging flies lose middle-term memory

R. John Davenport

Key Words: amnesiacduncerutabagaradish • Pavlovian olfactory conditioning

Elderly flies lose the capacity to identify evil odors, but memories don't flee immediately after the insects take a sniff, according to new research. The work reveals that old age impairs a middle stage of memory storage, and it links the deficit to a known memory-control gene. The connection provides a starting point for deciphering why brain retention falters with age.

Cognitive decay from Alzheimer's disease or other forms of dementia is a horrific prospect, but more commonly, memory worsens due to old age rather than disease (see "All in Your Mind"). Researchers are just beginning to track down age-related brain changes and have enlisted model organisms such as rodents and fruit flies to dissect the mechanisms. Previous studies suggested that memory formation in the fruit fly Drosophila melanogaster occurs in stages after a learning test. In the new work, Tamura and colleagues investigated which steps aging impairs.

The researchers gave a common recall test to fruit flies of various ages--from youthful 1-day-old flies to nearly dead 50-day-olds. They trained flies to associate a particular odor with an electric shock, then they tested the animals' aversion to the odor at different times after the training session. One hour after training, 20-day-old flies showed significantly poorer memory than did 1- or 10-day-old insects, and older flies performed even worse. Immediately after the training, however, approximately the same percentage of insects in each age group scurried away from the odor; 7 hours later, memory had deteriorated to the same degree in all the groups. Together the results suggest that aging doesn't alter either short-term or more persistent memory of the odor-shock connection, but it does degrade "middle-term" memory.

Further experiments revealed that the pattern of memory loss in aged flies mirrors that observed in flies with mutations in amnesiac, a gene that, when damaged, hinders middle-term memory. To determine whether the defective version of amnesiac contributes to age-related memory loss, the team performed the same odor-learning test in old amnesiac mutant flies. One hour after training, the middle-term memory time point, old and young mutants displayed the same degree of memory loss. Mutations in genes that disrupt other stages of memory did not erase a decline in memory with age, however. Together, the results suggest that age-related memory loss and glitches in amnesiac disrupt the same circuitry.

"The study characterizes for the first time age-dependent decline in memory" in a system that's easy to manipulate genetically, says Mani Ramaswami, a molecular biologist at the University of Arizona in Tucson. Molecular neuroscientist Ronald Davis of Baylor College of Medicine in Houston, Texas, agrees and says "they've put together a convincing case" that age-related memory loss mirrors that of amnesiac mutants. The amnesiac gene encodes a neuropeptide that cranks up production of a signaling molecule. Both researchers note that although amnesiac mutants stop making the neuropeptide, old flies still produce it, suggesting that aging snarls a later step in the pathway spurred by the molecule. Probing that idea might help reveal why fly--and perhaps human--memories become fleeting with age.

--R. John Davenport

December 10, 2003
  1. T. Tamura et al., Aging specifically impairs amnesiac-dependent memory in Drosophila. Neuron 40, 1003-1011 (2003). [Abstract] [Full Text] [Medline]
Citation: R. J. Davenport, What's That Smell? Sci. Aging Knowl. Environ. 2003 (49), nw168 (2003).

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