The “bug room” at National Tsing Hua University’s Brain Research Center doesn’t even take up 1 ping (3.3 square meters), but it’s jam-packed with hundreds of test tubes containing Drosophila whose genes have been altered in every way imaginable. Some have been given bulimia, and others Parkinson’s disease, while still others have been bred to have insomnia. There are even homosexual fruit flies.

These tiny creatures hold the key to curing some of mankind’s most implacable diseases, and fruit-fly memory in particular offers crucial insights.

Easy to cultivate and champion breeders, Drosophila melanogaster possess only four pairs of chromosomes and 100,000 neurons. Their simplicity combined with their capacity to produce a wide range of mutations has made them one of the most thoroughly studied organisms in all of genetics. (lower photo by Pan Jianhong)

Chen Chun-chao, a PhD candidate at NTHU’s Institute of Biotechnology, explains that neuroscientists identified long ago the main area of the human brain where memories are stored—the cerebral cortex—but trying to determine which of the brain’s 100 billion neurons are engaged in any specific task is like finding a needle in a haystack, writ large.

Fortunately, in terms of basic survival behavior, there isn’t a whole lot separating human beings from Drosophila, yet the flies’ network of neural pathways is considerably simpler. This means that by studying fruit flies, scientists can conjecture intelligently about the mechanisms governing long-term memory storage in the human brain.

Fruit flies, of course, have no ability to communicate with humans, so how do researchers know whether they form memories at all, let alone fix the precise location where they are stored?

The most common—and most effective—method for discerning such things is so-called “classical conditioning,” which involves learning through association. In the case of Drosophila, scientists exposed a group of flies 10 times to two different scents, one leading to a 60-volt electric shock and another completely neutral. In the tests conducted the following day, 70% of them were able to choose the benign smell, a clear indicator of their capacity for long-term memory storage.

The formation of memory in animals requires the building of new proteins. In previous tests, scientists discovered that if a protein inhibitor was applied during the flies’ “study periods,” they were more prone to forgetting the correct solution the following day.

“The only problem with that approach is that the inhibitor reduces protein levels across the board—in the end you can’t tell which cells are involved in forming memory,” explains Chen.

The researchers at NTHU addressed the problem through the tactic of gene control. They applied ricin, a protein inhibitor, only to specific neurons potentially involved in memory.

Much to everyone’s surprise, when they applied the inhibitor to the region commonly believed to be the seat of long-term Drosophila memory, the 2,500 neuron-strong corpora pedunculata or “mushroom bodies,” there was no impact; but when they directed the same strategy towards the dorsal-anterior-lateral (DAL) neurons, the flies’ performance was considerably reduced.

They discovered that the DAL had at least two groups of genes involved in long-term memory: during each of the flies’ test runs, “­CaMKII” and “period” were activated, signifying the participation of these neurons in memory formation.

Brain Research Center director Chiang Ann-shyn points out that current treatment of neurodegenerative diseases like Parkinson’s, Alzheimer’s, and Huntington’s is limited to drugs which retard the progress of the illness. The work being done now, however, may allow scientists and pharmaceuticals companies to develop more effective small-molecule drugs.

Their research also disclosed that Drosophila that were allowed adequate rest during the test period considerably outperformed those that were forced to “study” nonstop. These findings tally well with similar research done on human rest and learning.

“It doesn’t matter whether we’re dealing with fruit flies or people—excessive fatigue is detrimental to learning. So, listen up parents: Don’t make your kids stay up all night studying if you want to achieve optimal results!” quips Chiang.

Seymour Benzer, one of the great pioneering behavioral geneticists, once ecstatically described Drosophila neurons as “a hundred thousand angels dancing on the head of a pin.” The mystical choreography of these angels illuminates the subtlest workings of the human mind.