The Network Is the Clock

Circadian rhythms can be explained as every clock neuron has its own 24-hour timer, running through the same loops over and over throughout the day. But the researchers in the Guerrero & Cavanaugh (2025) study challenge that idea about the Drosophila lateral posterior neurons (LPNs). In the study, the researchers deleted the internal clock machinery inside the LPN neurons using CRISPR. What would be expected is that it would completely ruin the fly’s daily rest activity pattern. However, it doesn't, and the flies still showed normal circadian behavior. LPNs were still firing in a rhythm, even though their internal clock genes were gone. What actually disrupted the rhythm was silencing the neurons entirely. Once the researchers used Kir2.1 to shut down the LPNs, the flies rest activity rhythms got weak, and their sleep structure changed. That finding meant the timing didn’t come from inside the LPNs, but from the network they are connected to. LPNs are able to send and receive signals, while the rest of the circadian system puts them into rhythm. They aren’t really “clock cells” because of their own internal clock, but are clock cells because the network connection makes them clock cells.

A 2025 review in the NPJ Biological Timing and Sleep makes a similar point but in mammals, including humans. The review explains that the Suprachiasmatic Nucleus (SCN) acts as the brain's master clock. The review explained how SCN neurons don't have strong enough oscillators on their own, and human clock neurons also depend on the network of signals instead of their own independent internal clocks. Once you compare these two studies to each other, the connection is obvious. Flies and humans, two very different species, both show that circadian rhythms come from communication of a neural network, not just from the genetics of a single clock cell. The fly LPNs keep time even without their clock genes because the rest of the circuit forces them into sync. Human SCN neurons are doing a similar thing. Weak lone rhythms are put back into rhythm because the network couples them together to create our circadian rhythms.

The reason this comparison is interesting is that it changes the old view of how the clocks for our circadian rhythm are multiple clocks running independently is actually not fully accurate. There is an entire circadian rhythm system that works to keep the right rhythm pattern and keep it stable. Losing the molecular clock in some neurons is not as catastrophic or bad because the network has and will be kept in check by the entire circadian system. Just like the fly study used a cell with no clock to reveal how important the network is in keeping the circadian rhythm, the human review shows the same thing, just on a bigger scale. Both of the studies point to the same idea that circadian rhythms are less about single genes and more about the linkage of neurons to each other to maintain their clock.

Works Cited:

Guerrero G, Cavanaugh D, et al. The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest–activity rhythms. Neurobiology of Sleep and Circadian Rhythms. 2025.

Mendoza J. Brain circadian clocks timing the 24h rhythms of behavior. npj Biological Timing and Sleep. 2025;2:13. https://doi.org/10.1038/s44323-025-00030-8