The circadian rhythm is responsible for organizing countless physiological and behavioral processes across many species. During his talk Dan Cavanaugh emphasized that circadian rhythms are not controlled by just one singular cell, but instead, it comes from the activity of many coordinated neurons working together. In his paper “The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms” (Cavanaugh et al., 2025), demonstrated this network-based idea in what I found a really surprising way: some neurons that participate in circadian timing don’t actually need their individual molecular clocks to regulate daily behavior. This challenged the common assumption that every clock neuron must keep track of time within themselves.
In Drosophila (flies), about 240 clock neurons form a network that coordinates daily patterns of activity. Cavanaugh focused on a subset called the lateral posterior neurons (LPNs). These neurons were thought to rely on their own intrinsic molecular clocks to support circadian behavior. However, by genetically disrupting the molecular clock only within LPNs, Cavanaugh et al. found that transitions, and rest-activity structure remained despite the absence of an intrinsic clock in these cells. The reason is that the LPNs receive timing cues from other clock neurons, they don’t just function alone. But when Cavanaugh silenced the LPN completely using neuronal inhibition, the flies’ circadian rhythms weakened significantly. This shows that communication within the network is more essential than each neuron having its own cycle (Cavanaugh et al., 2025).
This network-based view of circadian timing is similar in human neuroscience. In his article from 2025, “Brain circadian clocks timing the 24 hour rhythm of behavior,” Mendoza reviews recent research showing that human circadian rhythms also comes from suprachiasmatic nucleus (SCN) which is traditionally described as the “master peacemaker,” Mendoza explains that many other brain regions, including the hypothalamus, brainstem, and cortex, contain their own molecular clocks that interact with one another. These regions communicate through hormonal, metabolic, and neural pathways to generate a stable 24 hour rhythm (Mendoza, 2025). Just like the flies, coordination among nodes is seen to be more important than perfecting timing within every individual node.
What makes the two papers connect so well is their combined message that circadian rhythms are at their core network phenomena. Cavanaugh’s LPN study illustrates this idea on a cellular level that shows some neurons can lose their intrinsic clock without disrupting behavior because the rest of the network carries them. Mendoza’s review expands on this concept just on a larger scale–the human brain. This highlighted that the circadian stability depends on synchrony and communication, not isolated oscillators. When that communication fails in these systems, and rhythms break down, whether that is in a small fly or across the human brain.
The broader message of these findings are the most important. Understanding the circadian system as a distributed network helps explain why sleep and activity rhythms usually hold up to cellular-level distributions, but are still extremely sensitive to metabolic disorders. Both papers emphasize that future research should look into going beyond singular cells or singular genes and rather look into how circadian information is transmitted, integrated and lined up across the system.
Together, Cavanaugh’s seminar and the research papers discussed in this post reinforce and back up the idea that biological timing isn’t focused on having perfect clocks in all individual neurons but it's more so about how those neurons can communicate with one another. Whether it's in flies or humans the brain is able to keep timing via the collaborative activity of the neurons.
References
Cavanaugh, D. J., Guerrero, C. Y. P., Cusick, M. R., Samaras, A. J., & Shamon, N. S. (2025). The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms. Neurobiology of Sleep and Circadian Rhythms, 18, 100124. https://doi.org/10.1016/j.nbscr.2025.100124
Mendoza, J. (2025). Brain circadian clocks timing the 24 h rhythms of behavior. NPJ Biological Timing & Sleep, 2(1). https://www.nature.com/articles/s44323-025-00030-8
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