No neuralyzer needed: The molecular pathways and circuit that trigger forgetting in C. elegans

Four hours after learning two smells, a tiny worm can forget one and still remember the other. In experiments at Kyushu University in Fukuoka, researchers traced how the nematode C. elegans selectively erases a memory of diacetyl while keeping its memory of isoamyl alcohol intact.

The finding, published in Current Biology, offers a close look at forgetting as an active process rather than a simple failure of memory. Scientists have learned a great deal about how memories form and last, but less about how the brain chooses which ones to let go. Forgetting can help an animal adapt, and understanding its biology may reveal how the brain manages memories.

C. elegans is a useful animal for this work because its nervous system has just 302 neurons, and each one has been identified. The worms are blind, but have a strong sense of smell. That makes it possible to follow a smell memory through a small, mapped network of nerve cells.

The Kyushu team built on earlier work from 2013, which showed that AWA neurons hold the memory of an odor and that signals from AWC neurons can erase it. The missing piece was the signal that started the process. First author Yuuki Onishi, a Ph.D. candidate, led the effort to identify it.

The researchers found that AWC neurons release a neuropeptide, a small signaling molecule, called NLP-47. It activates a receptor named GNRR-1 on AIZ neurons. AIZ then releases glutamate, a chemical messenger that acts on the GLR-4 receptor in AWA, where the odor memory is stored. This relay switches on the forgetting of that specific smell.

To test memory, the team trained worms to recognize diacetyl and later presented the smell again. Their response showed whether the memory remained or had faded. In a separate test, worms learned diacetyl and isoamyl alcohol at the same time. Four hours later, the diacetyl memory had faded, while the isoamyl alcohol memory remained. The circuit did not simply wipe out everything learned in that session.

The researchers also used optogenetics, a method that controls nerve-cell activity with light, to suppress AWC and AIZ. The worms then became more resistant to forgetting, supporting the role of those neurons in the process. Together, the results point to a specific chemical route that can weaken one stored odor memory without disturbing another learned alongside it.

Professor Takeshi Ishihara, who led the study at Kyushu University's Faculty of Science, said forgetting deserves attention alongside memory formation and storage. The team’s work does not mean that a complex human memory works like a worm’s odor memory. But by mapping a simple nervous system in detail, researchers can ask precise questions about how selective forgetting is controlled. The next challenge is to understand what decides which memories enter this pathway and how broadly similar mechanisms may apply in other brains.