Cold and lithium delay forgetting of olfactory memories in Caenorhabditis elegans
The persistence of memory reflects not only how it is formed but also how forgetting is delayed. The mechanisms controlling forgetting remain obscure, and in particular it is unclear to what degree this process is actively regulated. We discovered that cold exposure delays forgetting of specific olfactory memories by more than eight-fold and that adaptation to cold abolishes this effect. To study the underlying mechanism, we performed RNA sequencing, mutant analyses and pharmacological assays. Here we show that regulation of membrane properties underlies the presence and absence of cold-induced delayed forgetting. Furthermore, lithium can also delay forgetting in cold-sensitive worms but not in cold-tolerant worms; this effect involves downregulation of the diacylglycerol pathway in AWC neurons and long-term suppression of activity in the downstream AIY interneurons. Thus, the genetic tractability of worms might be harnessed to study the mechanism of action of lithium and cold exposure and, more fundamentally, how memory is stored and lost.
Authors
- Dror Cohen (ORCID: https://orcid.org/0000-0002-5077-2207)
- Guy Teichman (ORCID: https://orcid.org/0000-0003-2285-1343)
- Yehuda Salzberg (ORCID: https://orcid.org/0000-0003-0605-8038)
- Meital Oren‐Suissa (ORCID: https://orcid.org/0000-0001-9937-8326)
- Priti Agarwal (ORCID: https://orcid.org/0000-0003-0767-5951)
- Hagar Setty (ORCID: https://orcid.org/0000-0002-6857-4583)
- Itai Rieger (ORCID: https://orcid.org/0009-0000-9635-2147)
- Nina S. Levy
- Oded Rechavi (ORCID: https://orcid.org/0000-0001-6172-3024)
- Dror Sagi (ORCID: https://orcid.org/0000-0003-2125-3368)
- Anat Ben‐Zvi (ORCID: https://orcid.org/0000-0003-2477-6519)
- Hila Gingold
- Antonio Miranda–Vizuete (ORCID: https://orcid.org/0000-0002-6856-5396)
- Vladyslava Pechuk (ORCID: https://orcid.org/0000-0002-2813-4997)
- Ronen Zaidel‐Bar (ORCID: https://orcid.org/0000-0002-1374-5007)
- Sarit Anava (ORCID: https://orcid.org/0009-0008-2084-7643)
- Evelina I. Nikelshparg (ORCID: https://orcid.org/0000-0002-9258-938X)
- Kesem Goldstein
- Dana Landschaft-Berliner (ORCID: https://orcid.org/0009-0003-9920-693X)
Institutions
- Ben-Gurion University of the Negev (IL)
- Tel Aviv University (IL)
- National Centre for Biological Sciences (IN)
- Agricultural Research Organization (IL)
- Instituto de Biomedicina de Sevilla (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Weizmann Institute of Science (IL)
- Universidad de Sevilla (ES)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1038/s41593-025-02143-6
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Azrieli Foundation
- National Institutes of Health
- Kreitman School of Advanced Graduate Studies, Ben-Gurion University of the Negev