Sleep-wake patterns in most adult animals are controlled by the circadian rhythm, a network of genes and proteins that act like an internal clock, but these patterns cycle independently of this clock in early life in many of these species.1,2 How sleep comes under circadian control and its advantages remains poorly understood. Matthew Kayser, a sleep scientist at the University of Pennsylvania, uses fly larvae to explore the relationships between behavioral patterns, the circadian rhythm, and development in early life. 

In a recent article, Kayser and his team identified the time that sleep synchronized to this circadian clock in larvae and showed that this prompted long-term memory formation in the animals.3

     A confocal microscopy image of a larval fly brain lobes shows that arousal neurons, labeled in green, are concentrated at the top of the lobe and clock neurons, labeled in red, extend down the far side of the lobe away from the center and arousal neurons.
Researchers in the Kayser lab studied arousal neurons (green) and clock neurons (red) in stage three larval brains to explore when sleep synchronized to the circadian rhythm.
Amy Poe

The researchers quantified sleep duration and frequency in mid to late larval stages by visualizing neurons and assessing their connections during development. They found that neurons responsible for arousal acted independently of clock signals until late in the last developmental stage when they physically connected to clock neurons. 

“As soon as that happens, then suddenly that arousal cue that's unchecked comes under control of our timing mechanisms,” Kayser said.

Circadian-controlled sleep allowed for deeper sleep, which promotes memory formation in adult flies, so the team investigated if circadian-controlled sleep influenced this in larvae.4 Using an odor conditioning assay, the team found that only larvae in the last developmental stage formed a long-term memory after training.

“The level and quantity of evidence they brought to really tracing that circuit—it's so definitive,” said Michael Antle, a chronobiologist who studies circadian rhythms in rodents at the University of Calgary and was not involved in the study. 

Kayser’s team next intends to study the trigger that promotes the connection between arousal and clock neurons.


  1. Vitaterna MH, et al. Alcohol Res Health 2001;25(2):85-93
  2. Wager-Smith K, Kay SA. Nat Genet. 2000;26(1): 23-27
  3. Poe AR, et al. Sci Adv.2023; 9(36)eadh2301
  4. Dag U, et al. Neuroscience. 2019;8:e42786