Researchers at Kyushu University have identified molecular and neural pathways that allow the nematode Caenorhabditis elegans to actively forget a learned smell. The findings reveal how the worm can erase one memory without necessarily affecting others.
The team found that the neuropeptide NLP-47, released by AWC sensory neurons, activates the GNRR-1 receptor on AIZ neurons. AIZ neurons then release glutamate, which acts on GLR-4 receptors on AWA neurons, where the odor memory is stored. This signaling sequence leads to the memory’s erasure.
To study forgetting, researchers trained the worms to recognize diacetyl, an odor they are naturally attracted to. They later exposed the animals to the smell again and assessed whether they still moved toward it. The team built on earlier work identifying AWA as the memory-storing neurons and AWC as a source of signals that erase that memory.
In experiments involving two odors, diacetyl and isoamyl alcohol, the pathway promoted forgetting of the diacetyl memory while leaving the isoamyl alcohol memory intact. Worms in which NLP-47, GNRR-1 or glutamate signaling was disrupted were more resistant to forgetting. Suppressing AWC and AIZ neuron activity also made the animals less likely to forget.
The study’s senior author, Takeshi Ishihara, said memory research has focused more on how memories form and persist than on how they are lost. The researchers say their findings offer a framework for understanding how specific memories can be selectively eliminated. They note that GNRR-1-like receptors are found in other organisms, including humans, but their role in memory there remains unknown.
The research was published in Current Biology under the title “Neuropeptidergic-glutamatergic circuit regulates selective forgetting of olfactory learning.” The authors suggest the work may help inform future studies of disorders associated with dysregulated forgetting, including dementia and PTSD.}