scholarly journals Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity

Author(s):  
Benjamin Chew ◽  
Jae Ryun Ryu ◽  
Teclise Ng ◽  
Dongliang Ma ◽  
Ananya Dasgupta ◽  
...  
2008 ◽  
Vol 15 (4) ◽  
pp. 252-260 ◽  
Author(s):  
C. Kluge ◽  
C. Stoppel ◽  
C. Szinyei ◽  
O. Stork ◽  
H.-C. Pape

2016 ◽  
Vol 41 (12) ◽  
pp. 2862-2871 ◽  
Author(s):  
Ana Patrícia Simões ◽  
Nuno J Machado ◽  
Nélio Gonçalves ◽  
Manuella P Kaster ◽  
Ana T Simões ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Iyo Koyanagi ◽  
Kazuhiro Sonomura ◽  
Toshie Naoi ◽  
Takaaki Ohnishi ◽  
Naoko Kaneko ◽  
...  

AbstractMetabolites underlying brain function and pathology are not as well understood as genes. Here, we applied a novel metabolomics approach to further understand the mechanisms of memory processing in sleep. As hippocampal dentate gyrus neurons are known to consolidate contextual fear memory, we analyzed real-time changes in metabolites in the dentate gyrus in different sleep–wake states in mice. Throughout the study, we consistently detected more than > 200 metabolites. Metabolite profiles changed dramactically upon sleep–wake state transitions, leading to a clear separation of phenotypes between wakefulness and sleep. By contrast, contextual fear memory consolidation induced less obvious metabolite phenotypes. However, changes in purine metabolites were observed upon both sleep–wake state transitions and contextual fear memory consolidation. Dietary supplementation of certain purine metabolites impaired correlations between conditioned fear responses before and after memory consolidation. These results point toward the importance of purine metabolism in fear memory processing during sleep.


2021 ◽  
Vol 15 ◽  
Author(s):  
Madeline Musaus ◽  
Kayla Farrell ◽  
Shaghayegh Navabpour ◽  
W. Keith Ray ◽  
Richard F. Helm ◽  
...  

Strong evidence supports that protein ubiquitination is a critical regulator of fear memory formation. However, as this work has focused on protein degradation, it is currently unknown whether polyubiquitin modifications that are independent of the proteasome are involved in learning-dependent synaptic plasticity. Here, we present the first evidence that atypical linear (M1) polyubiquitination, the only ubiquitin chain that does not occur at a lysine site and is largely independent of the proteasome, is critically involved in contextual fear memory formation in the amygdala in a sex-specific manner. Using immunoblot and unbiased proteomic analyses, we found that male (49) and female (14) rats both had increased levels of linear polyubiquitinated substrates following fear conditioning, though none of these protein targets overlapped between sexes. In males, target protein functions involved cell junction and axonal guidance signaling, while in females the primary target was Adiponectin A, a critical regulator of neuroinflammation, synaptic plasticity, and memory, suggesting sex-dependent functional roles for linear polyubiquitination during fear memory formation. Consistent with these increases, in vivo siRNA-mediated knockdown of Rnf31, an essential component of the linear polyubiquitin E3 complex LUBAC, in the amygdala impaired contextual fear memory in both sexes without affecting memory retrieval. Collectively, these results provide the first evidence that proteasome-independent linear polyubiquitination is a critical regulator of fear memory formation, expanding the potential roles of ubiquitin-signaling in learning-dependent synaptic plasticity. Importantly, our data identify a novel sex difference in the functional role of, but not a requirement for, linear polyubiquitination in fear memory formation.


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