Long Term Memory of Smell in C. elegans

     Sleep-wake rhythms are one of the most prominent behaviors seen in humans and can have a tremendous impact on one’s daily functions. The scientific community is extremely interested in the relationship between sleep and its advantages, specifically how it could contribute to long-term memory retention. 

    In the article “Developmental emergence of sleep rhythms enables long-term memory capabilities in Drosophila” Daniel Cavanaugh and his research team seek to pinpoint the exact development stage when young animals begin to develop their circadian clock. They found that this occurs during the third instar larvae stage (L3), where a concrete relationship is formed between DN1a clock neurons and arousal-promoting Dh44 neurons. During the third stage, larvae experience “a higher proportion of longer sleep bouts” and when experimented with constant sleep conditions, the molecular clock was disrupted. Additionally, the article explains how the formation of a concrete circadian clock can aid in long-term memory retention. Since 3rd instar larvae experience deeper sleep, this in turn improves their memory retention. This was seen when researchers used a high-intensity light stimulus to mess up the larvae’s circadian clock and make them sleep-deprived. This loss of sleep disrupted their long-term memory retention. As a result of these experimental manipulations, researchers concluded that the circadian clock is formed during L3, and the presence of this system causes long-term memory retention to occur. 

    A similar research study aimed to show how a loss of sleep could impact the memory of smell in C. elegans. Hanna Zwaka, a neuroscientist at Harvard University in Cambridge, Massachusetts wanted to use these worms since they are simple organisms, containing only 302 neurons. Researchers know the individual synapses present in these organisms, which is something that could help them better understand the underlying mechanism behind sleep and memory retention. To test the memory of these worms, researchers trained the worms to ignore the smell of butanone (a compound they normally find attractive) by associating it with the removal of food. Worms that were allowed to rest after training were shown to detect the odor using a neuron called AWC, which connects to a pair of neurons called AIY. Training the worms to avoid the odor resulted in a decrease in AWC-AIY synapses. Some worms were refrained from resting after undergoing the training. These worms were disrupted from their sleep by gently shaking them or removing food from their environment. Determining if a worm was asleep or not was tricky, but researchers used video-based imaging tools to detect certain behaviors of worms that were sleeping. They found that asleep worms had a straight body, besides a crook in their neck and they enjoyed sleep eating. Worms that were not allowed to sleep showed a stronger synaptic connection between AWC and AIY neurons. Researchers concluded that for a smell to become a solidified memory in worms, they have a critical 1-2 hour window for them to sleep after training occurs. When that sleep is disturbed, memory retention is not preserved.

    Both of these research articles show a correlation between sleep and memory retention. In Cavanugh’s research, he demonstrated that it was only during the L3 stage, that long-term memory was established in Drosophila. This function did not occur before this stage because the larvae had not established a circadian clock yet. Without proper, uninterrupted, deep sleep, the brain is not able to hold onto long-term memories. This is also exhibited in Zwaka’s research, where she showed that C.elegans were able to remember the negative association of the butanone smell after they had successfully taken a nap after training. Without the consolidation given through sleep, the worms were not able to remember this connection. Both of these research studies are helpful in better understanding the advantages of sleep when it comes to long-term memory retention 

References:

1. 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). Developmental emergence of sleep rhythms enables long-term memory in Drosophila. Science advances, 9(36), eadh2301. https://doi.org/10.1126/sciadv.adh2301

2. Chandra, R. et al. Cell https://doi.org/10.1016/j.cell.2023.05.006 (2023).

3. https://www.nature.com/articles/d41586-023-01849-6