PMID- 25404896
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141118
LR  - 20200930
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 8
DP  - 2014
TI  - Elevated activation of CaMKIIalpha in the CPEB3-knockout hippocampus impairs a 
      specific form of NMDAR-dependent synaptic depotentiation.
PG  - 367
LID - 10.3389/fncel.2014.00367 [doi]
LID - 367
AB  - Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a 
      sequence-specific RNA-binding protein that confines the strength of glutamatergic 
      synapses by translationally downregulating the expression of multiple 
      plasticity-related proteins (PRPs), including the N-methyl-D-aspartate receptor 
      (NMDAR) and the postsynaptic density protein 95 (PSD95). CPEB3 knockout (KO) mice 
      exhibit hippocampus-dependent abnormalities related not only to long-term spatial 
      memory but also to the short-term acquisition and extinction of contextual fear 
      memory. In this study, we identified a specific form of NMDAR-dependent synaptic 
      depotentiation (DPT) that is impaired in the adult CPEB3 KO hippocampus. In 
      parallel, cultured KO neurons also exhibited delayed morphological and 
      biochemical responses under NMDA-induced chemical long-term depression (c-LTD). 
      The c-LTD defects in the KO neurons include elevated activation of 
      calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIalpha), increased 
      Ser831 phosphorylation of GluA1 and slow degradation of PSD95 and GluA1. Because 
      transient pharmacological suppression of CaMKIIalpha activity during the 
      DPT-initiating phase successfully reversed the LTP in the KO hippocampus, DPT and 
      c-LTD in the two different systems shared common molecular defects due to the 
      absence of CPEB3. Together, our results suggest that CPEB3 deficiency imbalances 
      NMDAR-activated CaMKIIalpha signaling, which consequently fails to depress synaptic 
      strength under certain stimulation conditions.
FAU - Huang, Wen-Hsuan
AU  - Huang WH
AD  - Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.
FAU - Chao, Hsu-Wen
AU  - Chao HW
AD  - Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.
FAU - Tsai, Li-Yun
AU  - Tsai LY
AD  - Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.
FAU - Chung, Ming-Hung
AU  - Chung MH
AD  - Interdisciplinary Program of Life Sciences, National Tsing Hua University 
      Hsinchu, Taiwan.
FAU - Huang, Yi-Shuian
AU  - Huang YS
AD  - Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20141103
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC4217494
OTO - NOTNLM
OT  - CPEB
OT  - CaMKII
OT  - NMDAR
OT  - depotentiation
OT  - synaptic depression
EDAT- 2014/11/19 06:00
MHDA- 2014/11/19 06:01
PMCR- 2014/01/01
CRDT- 2014/11/19 06:00
PHST- 2014/06/24 00:00 [received]
PHST- 2014/10/16 00:00 [accepted]
PHST- 2014/11/19 06:00 [entrez]
PHST- 2014/11/19 06:00 [pubmed]
PHST- 2014/11/19 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2014.00367 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2014 Nov 3;8:367. doi: 10.3389/fncel.2014.00367. eCollection 
      2014.