A pioneering study conducted at Brandeis has shed light on seasonal behavioral changes in fruit flies, knowledge that could eventually translate into a better understanding of seasonal physical and mental changes in humans that occur between the brighter and darker months.The study-published April 6 in Cell, a leading biology journal-showed that the neurons which control the fruit fly's daily rhythm of sleep and activity, known as the circadian rhythm, form a network that underlies the insect's seasonal behavior adjustments. The model proposed by the study is the first experimentally based explanation of seasonal adaptation.

In two earlier papers, the same research team established that one group of cells governed the flies' behavior in the morning, while another governed their evening behavior. Prof. Michael Rosbash (BIO), whose National Center for Behavioral Genomics lab conducted the study, called the latest work the "culmination of this trilogy."

Prof. Jeffrey Hall (BIO), who will retire after this year, was a major contributer to this research.

The current study suggests a connection between depression and biological rhythm. In it, researchers show that a gene called "shaggy" goes to make up a key part of the pathway traveled by light to the brain centers that affect circadian behavior.

Though researchers said more work needs to be done to determine whether this discovery could apply to humans and other mammals, Dan Stoleru, the study's lead author, said one potential application of the research could be the treatment of seasonal depression.

Previous studies have shown that lithium-a medicine used to treat various depressive disorders-targets gene GSK-3, essentially the human equivalent of shaggy, Rosbash said. The relationship of GSK-3 with both lithium and light has intrigued researchers, Stoleru said, because exposure to specific amounts of light has been suggested as another effective therapy for depression in general and seasonal depression in particular.

Stoleru, a postdoctoral fellow working under Rosbach, said that while working on his second paper, he was surprised to notice that the flies became indifferent to changes in light when he manipulated them to overexpress shaggy, meaning they produce more than the normal amount of shaggy protein.

Jerome Menet, another of the study's authors and also a postdoctoral fellow, said that even though the flies' vision was preserved after shaggy was overexpressed, light no longer affected their sleep-wake pattern.

While ordinary flies exposed to constant light normally become "insomniacs," Rosbash said, the flies that overexpressed shaggy continue to operate as if there were an alternation between light and dark.

"The question was, 'What was the biological meaning of this?'" Rosbash said.

The current study, "The Drosophila Circadian Network Is a Seasonal Timer," looked for an answer to that question by placing the flies in tubes with motion detectors that recorded their activity patterns, Menet said.

The researchers mimicked the summer by exposing the flies to 14 hours of light and 10 hours of dark and then winter by reversing that cycle. They observed the seasonal differences in the flies' behavior by monitoring shifts in the flies' peaks of activity at night and during the day.

In each "season," the researchers observed some flies with genetically-manipulated morning cells and others with genetically-modified evening cells. They found that during summers, the temporal pattern of behavior is driven by the evening cells, while morning cells generate the winter-specific pattern.

Rosbash said that theories have existed for years suggesting that seasonal behavior change would be provided by "two biochemically distinct clocks," as if the behavior of a person were timed by an analog and a digital watch. He added that the study suggested instead that the two clocks were "anatomically separate ... but not biochemically different.