Neuronal activity determines the protein synthesis dependence of long-term potentiation

2006 ◽  
Vol 9 (4) ◽  
pp. 478-480 ◽  
Author(s):  
Rosalina Fonseca ◽  
U Valentin Nägerl ◽  
Tobias Bonhoeffer
Keyword(s):  
Protein Synthesis ◽  
Neuronal Activity ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals Selective targeting of mRNA and the following protein synthesis of CaMKIIα at the long-term potentiation-induced site

Biology Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. bio042861
Author(s):  
Itsuko Nihonmatsu ◽  
Noriaki Ohkawa ◽  
Yoshito Saitoh ◽  
Reiko Okubo-Suzuki ◽  
Kaoru Inokuchi
Keyword(s):  
Protein Synthesis ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Selective Targeting

scholarly journals Synaptic Tagging and Capture: Differential Role of Distinct Calcium/Calmodulin Kinases in Protein Synthesis-Dependent Long-Term Potentiation

2010 ◽  
Vol 30 (14) ◽  
pp. 4981-4989 ◽  
Author(s):  
R. L. Redondo ◽  
H. Okuno ◽  
P. A. Spooner ◽  
B. G. Frenguelli ◽  
H. Bito ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Synaptic Tagging And Capture

scholarly journals Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation

2013 ◽  
Vol 109 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Charles A. Hoeffer ◽  
Emanuela Santini ◽  
Tao Ma ◽  
Elizabeth C. Arnold ◽  
Ashley M. Whelan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Translation Initiation ◽  
Translational Control ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
General Protein Synthesis ◽  
General Protein

Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes.

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