Abstract
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.
Funder
Ministry of Education, Culture, Sports, Science and Technology
JST CREST
Japan Society for the Promotion of Science
Shimadzu Science Foundation
Takeda Science Foundation
Kanae Foundation for the Promotion of Medical Science
Research foundation for Opto-Science and Technology
Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
Kato Memorial Bioscience Foundation
Japan Foundation for Applied Enzymology
SENSHIN Medical Research Foundation
Life Science Foundation of Japan
The Uehara Memorial Foundation
Brain Science Foundation
Kowa Life Science Foundation
Inamori Foundation
GlaxoSmithKline
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Molecular Biology
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