Understanding Circadian Rhythms

    In preparation for Dr. Cavanaugh’s talk for our class, we read the article “The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms” by Charlene Y.P. Guerrero et al. This article investigates the functions of lateral posterior neurons (LPNs) and its effects on circadian and sleep behavior. LPNs are one of hundreds of types of “clock” neurons involved in maintaining the overall circadian clock, but its primary functions are largely unknown. In the experiment, the researchers first used GAL4 to make a molecular product that could eliminate the production of PER/TIM proteins that drive an LPN’s individual circadian clock in Drosophila melanogaster. They monitored activity and sleep behavior throughout two conditions, light-dark (LD) and constant darkness (DD). This resulted in only slight changes in activity and sleep behavior compared to the control group in both conditions. Next, they used the GAL4-UAS system to drive expression of potassium channel Kir2.1, which hyperpolarized the LPNs and decreased their firing rate. This condition resulted in a significant decrease in sleep consolidation in the daytime in LD and during free-running in DD. The researchers concluded that LPNs are involved in maintaining proper locomotor activity rhythms with the rest of the clock neuronal network. It was also proposed that LPNs can take in input signals from other clock neurons, which is why hardly anything changed when its own circadian system was silenced. 

A similar experiment was performed in “Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons” by Sara Aton et al., which investigates the function of vasoactive intestinal polypeptides (VIPs) which are secreted by neurons in the superchiasmatic nucleus (SCN), the body’s “main circadian clock” . Like LPNs, the role of VIP is not fully understood, but it could be involved with rhythmicity and synchrony. In the experiment, VIP or its receptor Vipr2 was knocked out in lab mice while researchers monitored its activity and circadian behavior in LD and DD conditions. They found that the mutant mice still expressed circadian rhythms, but the SCN neurons showed a significant loss of rhythmicity and synchronization compared to the wild-type mice. 

Both of these research articles show a significant step in the field of neuroscience for slowly deciphering the functions of parts of our circadian clock. Many sleep disorders, such as insomnia, show negative behavioral and physiological symptoms that could be related to a deficit in the functions of circadian clock neurons. Fully understanding all the parts and processes of our circadian systems could be the key to potentially finding a cure for these disorders which affect millions of people. 

References:

    Guerrero, C. Y. P., Cusick, M. R., Samaras, A. J., Shamon, N. S., & Cavanaugh, D. J. (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

  

 Aton, S., Colwell, C., Harmar, A. et al. Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat Neurosci 8, 476–483 (2005). https://doi.org/10.1038/nn1419