CaMKII regulates proteasome phosphorylation and activity and promotes memory destabilization following retrieval. Neurobiol Learn Mem 2016 Feb;128:103-9
Date
01/19/2016Pubmed ID
26779588Pubmed Central ID
PMC4754128DOI
10.1016/j.nlm.2016.01.001Scopus ID
2-s2.0-84954515218 (requires institutional sign-in at Scopus site) 91 CitationsAbstract
Numerous studies have suggested that memories "destabilize" and require de novo protein synthesis in order to reconsolidate following retrieval, but very little is known about how this destabilization process is regulated. Recently, ubiquitin-proteasome mediated protein degradation has been identified as a critical regulator of memory trace destabilization following retrieval, though the specific mechanisms controlling retrieval-induced changes in ubiquitin-proteasome activity remain equivocal. Here, we found that proteasome activity is increased in the amygdala in a CaMKII-dependent manner following the retrieval of a contextual fear memory. We show that in vitro inhibition of CaMKII reversed retrieval-induced increases in proteasome activity. Additionally, in vivo pharmacological blockade of CaMKII abolished increases in proteolytic activity and activity related regulatory phosphorylation in the amygdala following retrieval, suggesting that CaMKII was "upstream" of protein degradation during the memory reconsolidation process. Consistent with this, while inhibiting CaMKII in the amygdala did not impair memory following retrieval, it completely attenuated the memory impairments that resulted from post-retrieval protein synthesis blockade. Collectively, these results suggest that CaMKII controls the initiation of the memory reconsolidation process through regulation of the proteasome.
Author List
Jarome TJ, Ferrara NC, Kwapis JL, Helmstetter FJAuthor
Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
ATPases Associated with Diverse Cellular ActivitiesAmygdala
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Conditioning, Classical
Fear
Male
Memory Consolidation
Mental Recall
Phosphorylation
Proteasome Endopeptidase Complex
Rats, Long-Evans
