title: Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors.
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 memory in the contextual fear conditioning test and long-term spatial memory in 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 hippocampus-dependent memories.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan and Taiwan International Graduate Program, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Hsu-Wen
authors.initials: HW
authors.lastname: Chao
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Tsai
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lu
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Lin
authors.forename: Wen-Hsuan
authors.initials: WH
authors.lastname: Huang
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Chou
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Lu
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Lin
authors.forename: Ping-Tao
authors.initials: PT
authors.lastname: Lee
authors.forename: Yi-Shuian
authors.initials: YS
authors.lastname: Huang
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D000076122:Disks Large Homolog 4 Protein; D005239:Fear; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D036881:Long-Term Synaptic Depression; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C477603:Cpeb3 protein, mouse; C501447:Dlg4 protein, mouse