Abstract
In contrast to the popular opinion that forgetting is only the opposite of learning and memory, active forgetting explains the intrinsic instability of a labile memory that lasts for hours and has its own signal transduction pathways. However, the detailed mechanisms underlying forgetting are still lacking, though the investigations available in this field offer the first insights into their regulation. To identify the alternative signaling pathways that control the process of forgetting, we used the short-term forgetting model of Caenorhabditis elegans and discovered the involvement of lev-10, a scaffolded transmembrane protein of L-AChR, by screening the candidate genes that potentially functioned in synaptic plasticity. The LEV-9/LEV-10/L-AChR functional complex was confirmed to participate in forgetting occurrence. Furthermore, EGL-9 functioned upstream of LEV-10 and negatively regulated the latter during forgetting. Meanwhile, EGL-9 was also the target of miR-51, and hence the mutation of miR-51 similarly affected the function of L-AChR and delayed the short-term forgetting. Our findings have identified an integrated signaling pathway responsible for active forgetting, which provides the new experimental evidence on the cholinergic forgetting signal.
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Acknowledgements
This work was supported by the National Natural Science Foundation Program of China (grant number 32170184) and the Department of Science and Technology of Yunnan Province (grant number 2019FA046).
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National Natural Science Foundation of China, 32170184, Xiaowei Huang, Yunnan Provincial Science and Technology Department, 2019FA046, Xiaowei Huang.
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XWH designed research; SZN and WHZ performed research; SZN, WHZ and YXL analyzed data; and XWH and SZN wrote the paper. All authors read and approved the final manuscript for publication.
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All data generated or analyzed during this study are included in the published paper and associated supplemental files. Sequencing data were deposited in the National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/) under the accession number PRJNA747144.
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Niu, S., Zhou, W., Li, Y. et al. The signaling pathway of levamisole-sensitive-acetylcholine receptors involved in short-term forgetting of Caenorhabditis elegans. Mol Genet Genomics 297, 1027–1038 (2022). https://doi.org/10.1007/s00438-022-01901-6
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DOI: https://doi.org/10.1007/s00438-022-01901-6