Cool worms delay forgetting – Environmentally induced inner state that extends memory retention in C. elegans nematodes

The Caenorhabditis elegans nematode has a very simple nervous system composed of just 302 neurons, and yet it is capable of forming associative memories. These memories, however, tend to fade quickly. In this work, we discovered that while at normal cultivation temperatures, worms typically forget associations between attractive odors and starvation after 2-3 hours, they are able to retain the memories for as long as they are cooled down on ice. However, as soon as the temperatures return to normal, the worms start forgetting again. We suspected this phenomenon might be biologically regulated, and not caused by an overarching reduction in enzymatic activity, since it was only observed for odors sensed by the AWC pair of sensory neurons. Indeed, environmental induction of cold tolerance had led the worms to lose their ability to delay forgetting when cooled. By combining whole-worm RNA sequencing and behavioral assessment, we identified multiple genes in the diacyl glycerol (DAG) pathway which are required for delayed forgetting on ice. The ASJ neuronal pair were found to regulate both cold tolerance and lithium sensitivity in the past. Interestingly, we found that treating worms with lithium, a drug used for decades to treat bipolar disorder, delays forgetting in cold-sensitive worms. In summary, we explore different cogs within the memory clock that can be adjusted to delay forgetting.