Circadian rhythms are a natural, internal, roughly 24 hour process that provides important advantages for organisms to adapt behavior to changing environmental conditions. Given how important it is for everyday life, it is imperative to understand how it works in other organisms, so that it may one day be applied to humans. Since fruit flies, otherwise known as Drosophila, share many functional aspects of circadian regulation with humans, they have been an important model organism for identifying how the circadian rhythmicity and cells that are regulated by clock function in the human body.
A fascinating subject of study in this field has to do with the specific relationship between sleep and memory, and in “Developmental emergence of sleep rhythms enables long-term memory capabilities in Drosophila” by Cavanaugh et al., there is not only a focus on studying the precise time point of circadian development in fruit flies, but also a focus on whether circadian developmental sleep differences are relevant and necessary for enduring, long-term (LT) memories. In the beginning of the study, they proposed that when circadian sleep developmentally emerges, it enables more complex cognitive processes, including the beginning of enduring memories. The study was able to uncover the importance of DH44 in maintaining timed arousal in larval 2nd instar, of the connection between DH44 neurons and DN1A neurons and how their connection maintains arousal under clock control, and of the CCHamide-1-receptor in maintaining rhythmic changes in sleep duration and bout number. Once these mechanisms are confirmed in the study and a pathway is traced in larval fruit flies, there is a shift in utilizing a two-odor reciprocal olfactory conditioning paradigm to test memory performance in both 2nd and 3rd instar larvae. In control fruit flies, short term memory was shown to not require the presence of sleep rhythms as a prerequisite, and a knockdown of CCHa1-R in DH44 neurons produced similar results in early 3rd instar larvae, providing further evidence for this fact. Then, to test for long term memory, they utilized a three odor-quinine training cycle to assess aversive long term memory. This test showed that 3rd instar larvae exhibited a strong persistent memory of the aversive cue. Additionally, when using two mutant lines that knocked out clock in the fruit fly bodies, the experiments showed that 3rd instar larvae long term memory is clock-dependent, due to their lack of ability to show long term memory. Additionally, in 3rd instar larvae, knockdown of CCHa1-R in DH44 neurons blocked long term memory, and failed to also exhibit increased arousal threshold that is normally seen in fruit flies during sleep. Further tests that utilized sleep deprivation in between training and tests displayed that long term memory was also disrupted in cases of sleep deprivation. The final finding in the paper, backed up with sufficient data from these experiments, is that early 3rd instar larvae is the part of a fruit fly life cycle where both sleep rhythms emerge, and where long term memory is facilitated.
These findings are mirrored and supported well in the article “The clock gene Per1 may exert diurnal control over hippocampal memory consolidation” by Lauren Bellfy et al. In this article, researchers used the hippocampus-dependent Object Location Memory task to experiment on how the phases of memory - acquisition, consolidation, and retrieval - were regulated across a 24 hour day. After findings confirming the diurnal changes of memory consolidation in mice, better long term memory performance in the day was confirmed, though acquisition and retrieval displayed no changes. However, an added layer of interest to their experiments showed that a mere knockdown of the circadian clock gene Per1 within the dorsal hypothalamus was enough to impact spatial memory, with no need to additionally impact circadian rhythmicity to induce that effect. In the mammalian brain, the suprachiasmatic nucleus regulates the brain’s clock, and Per1 neurons hold a known role in upkeeping that regulation. As such, due to its importance in maintaining rhythmicity, it may even exert diurnal control over memory consolidation in the dorsal hypothalamus.
Though mice and fruit flies have obvious differences between how researchers may conduct tests or impact certain internal structures, it’s interesting to see the similarities between the two articles, and how hyperspecific they both get in vastly different areas. The first article chooses to focus on how developmental circadian rhythmicity may impact sleep, while the second article chooses to focus on specific structures, the different parts of memory formation, and Per1 neurons. It goes to show how complicated the mechanisms behind both circadian rhythmicity and memory are, and how difficult that makes it to narrow down the true answer of what aspects of the concept of circadian rhythmicity impacts memory formation. The topic is vast, and holds potential for many experiments in the future.
References:
Poe, A. R., Zhu, L., Szuperak, M., McClanahan, P. D., Anafi, R. C., Scholl, B., Thum, A. S., Cavanaugh, D. J., & Kayser, M. S. (2023, September 8). Developmental emergence of sleep rhythms enables long-term memory in drosophila. Science advances. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491288/
Ramsey, R. by L. (2023, July 31). Circadian clock gene plays role in memory formation. News. https://www.news-medical.net/news/20230728/Circadian-clock-gene-plays-role-in-memory-formation.aspx
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