Elevated activation of CaMKIIalpha in the CPEB3 knockout hippocampus impairs a specific form of NMDAR-dependent synaptic depotentiation

Wen Hsuan Huang, Hsu-Wen Chao, Li Yun Tsai, Ming-Hung Chung, Yi-Shuian Huang

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18 Citations (Scopus)

Abstract

Cytoplasmic polyadenylation element binding protein (CPEB) 3 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 (PSD) 95. 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 (CaMKIIa), increased Ser831 phosphorylation of GluA1 and slow degradation of PSD95 and GluA1. Because transient pharmacological suppression of CaMKIIa activity during the DPT-initiating phase successfully reversed the long-term potentiation (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 CaMKIIa signaling, which consequently fails to depress synaptic strength under certain stimulation conditions.
Original languageUndefined/Unknown
Pages (from-to)367
Number of pages1
JournalFrontiers in Cellular Neuroscience
Volume8
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Elevated activation of CaMKIIalpha in the CPEB3 knockout hippocampus impairs a specific form of NMDAR-dependent synaptic depotentiation. / Huang, Wen Hsuan; Chao, Hsu-Wen; Tsai, Li Yun; Chung, Ming-Hung; Huang, Yi-Shuian.

In: Frontiers in Cellular Neuroscience, Vol. 8, 2014, p. 367.

Research output: Contribution to journalArticle

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abstract = "Cytoplasmic polyadenylation element binding protein (CPEB) 3 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 (PSD) 95. 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 (CaMKIIa), increased Ser831 phosphorylation of GluA1 and slow degradation of PSD95 and GluA1. Because transient pharmacological suppression of CaMKIIa activity during the DPT-initiating phase successfully reversed the long-term potentiation (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 CaMKIIa signaling, which consequently fails to depress synaptic strength under certain stimulation conditions.",
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AU - Chung, Ming-Hung

AU - Huang, Yi-Shuian

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AB - Cytoplasmic polyadenylation element binding protein (CPEB) 3 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 (PSD) 95. 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 (CaMKIIa), increased Ser831 phosphorylation of GluA1 and slow degradation of PSD95 and GluA1. Because transient pharmacological suppression of CaMKIIa activity during the DPT-initiating phase successfully reversed the long-term potentiation (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 CaMKIIa signaling, which consequently fails to depress synaptic strength under certain stimulation conditions.

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JO - Frontiers in Cellular Neuroscience

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