title: Cdc42-Dependent Forgetting Regulates Repetition Effect in Prolonging Memory Retention.
abstract: Repeated learning is used daily and is a powerful way to improve memory. A fundamental question is how multiple learning trials add up to improve memory. While the major studies so far of such a repetition effect have emphasized the strengthening of memory formation, the current study reveals a molecular mechanism through suppression of forgetting. We find that single-session training leads to formation of anesthesia-resistant memory (ARM) and then activation of the small G protein Cdc42 to cause decay or forgetting of ARM within 24 hr. Repetition suppresses the activation of Cdc42-dependent forgetting, instead of enhancing ARM formation, leading to prolonged ARM. Consistently, inhibition of Cdc42 activity through genetic manipulation mimicked the repetition effect, while repetition-induced ARM improvement was abolished by elevated Cdc42 activity. Thus, only the first session in repetitive training contributes to ARM formation, while the subsequent sessions are devoted not to acquiring information but to inhibiting forgetting.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Lianzhang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory for Orchid Conservation and Utilization, The National Orchid Conservation Center of China and The Orchid Conservation & Research Center of Shenzhen, Shenzhen 518114, China; The Center for Biotechnology and Biomedicine, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: zhongyi@tsinghua.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D004175:Diptera; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020559:Monomeric GTP-Binding Proteins