Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors

Hsu Wen Chao, Li Yun Tsai, Yi Ling Lu, Pei Yi Lin, Wen Hsuan Huang, Hsin Jung Chou, Wen Hsin Lu, Hsiu Chen Lin, Ping Tao Lee, Yi Shuian Huang

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Abstract

Long-term memory requires activity-dependent synthesis of plasticity-related proteins (PRPs) to strengthen synaptic efficacy and consequently consolidate memory. Cytoplasmic polyadenylation element binding protein (CPEB)3 is a sequence-specific RNA-binding protein that regulates translation of several PRP RNAs in neurons. To understand whether CPEB3 plays a part in learning and memory, we generated CPEB3 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent, short-term fear memoryin the contextual fear conditioning test and long-term spatialmemoryin the Morris water maze. The basal synaptic transmission of Schaffer collateral-CA1 neurons was normal but long-term depression evoked by paired-pulse low-frequency stimulation was modestly facilitated in the juvenile KO mice. Molecular and cellular characterizations revealed several molecules in regulating plasticity of glutamatergic synapses are translationally elevated in the CPEB3 KO neurons, including the scaffolding protein PSD95 and the NMDA receptors along with the known CPEB3 target, GluA1. Together, CPEB3 functions as a negative regulator to confine the strength of glutamatergic synapses by downregulating the expression of multiple PRPs and plays a role underlying certain forms of hippocampusdependent memories.

Original languageEnglish
Pages (from-to)17008-17022
Number of pages15
JournalJournal of Neuroscience
Volume33
Issue number43
DOIs
Publication statusPublished - 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chao, H. W., Tsai, L. Y., Lu, Y. L., Lin, P. Y., Huang, W. H., Chou, H. J., Lu, W. H., Lin, H. C., Lee, P. T., & Huang, Y. S. (2013). Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors. Journal of Neuroscience, 33(43), 17008-17022. https://doi.org/10.1523/JNEUROSCI.3043-13.2013