CAN FLIES TELL THE TIME?

Abstract

We all know the feeling - it's been a tough week of getting up early to go to work and you're looking forward to lying in on Saturday. However, your highly efficient internal body clock has other ideas and you are wide-awake and ready to go at 7 am. Circadian rhythms make sure that our bodies are ready for the day ahead and send us to sleep at night. Even the humble fruit fly has an internal clock, which determines when the fly is at its most active in a 24-hour cycle. Brigitte Grima and her colleagues in the Alfred Fessard Neurobiology Institute in France have teased apart how a Drosophila'sbrain controls its activity rhythms.The clock in a fly's brain consists of several groups of neurons that express a protein called Period. The study focused on two groups of these neurons: the lateral ventral neurons, which come in small and large varieties,and the lateral dorsal neurons. Besides expressing Period, most of the ventral neurons also express a protein called Pigment-dispersing factor (PDF), but dorsal neurons do not express this protein. A normal fruit fly kept in a 12 hours dark:12 hours light cycle will show peaks of activity just before and after the lights are turned on or off; however, a mutant fly that doesn't express Period has no such daily rhythms.The team decided to see how the dorsal and ventral clock neurons regulate the flies' morning and evening activity bouts. Starting off with a batch of non-Period expressing mutants, they created a range of mutant flies with restored Period expression in specific neurons in the flies' brains and saw how active each of these mutants were in different light conditions. By restoring Period-expression in different neuron types in each group of mutants, they hoped to identify the exact time-keeping role of each neuron type.The team found that when they restored Period expression in all the lateral ventral neurons in one type of mutant, the flies showed their morning peak of activity when the lights came on, but did not show an evening peak when they were plunged into darkness again 12 hours later. However, when Period expression was restricted to ventral neurons that were also expressing PDF in a different mutant fly, the morning peak of activity again returned, showing that the PDF-expressing lateral ventral neurons are sufficient to restore the morning alarm. The team honed the search down even further and showed that when Period was expressed in the large lateral ventral neurons only, the flies showed no morning or evening peak of activity. This suggests that the large ventral neurons only have an effect when the small ventral neurons are also expressing Period.When the team kept another batch of mutants in complete darkness for days and Period was expressed only in the small lateral ventral neurons, the flies still showed peaks of activity in the morning. This shows that the small lateral ventral neurons form the core of the fly's body clock and are able to form a basic rhythm, acting as a pacemaker even in complete darkness. Evening activity peaks were also dependent on activity in the morning: when Period was expressed in the lateral dorsal neurons the flies were active around lights off, but only when the ventral neurons responsible for morning activity were also expressing Period.The team think that the interaction between the stable pacemaker and the evening clock are vital for the fly to be able to respond to an uncertain environment, but still maintain a basic day-to-day rhythm.