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Publication : FoxO6 regulates memory consolidation and synaptic function.

First Author  Salih DA Year  2012
Journal  Genes Dev Volume  26
Issue  24 Pages  2780-801
PubMed ID  23222102 Mgi Jnum  J:191193
Mgi Id  MGI:5461238 Doi  10.1101/gad.208926.112
Citation  Salih DA, et al. (2012) FoxO6 regulates memory consolidation and synaptic function. Genes Dev 26(24):2780-801
abstractText  The FoxO family of transcription factors is known to slow aging downstream from the insulin/IGF (insulin-like growth factor) signaling pathway. The most recently discovered FoxO isoform in mammals, FoxO6, is highly enriched in the adult hippocampus. However, the importance of FoxO factors in cognition is largely unknown. Here we generated mice lacking FoxO6 and found that these mice display normal learning but impaired memory consolidation in contextual fear conditioning and novel object recognition. Using stereotactic injection of viruses into the hippocampus of adult wild-type mice, we found that FoxO6 activity in the adult hippocampus is required for memory consolidation. Genome-wide approaches revealed that FoxO6 regulates a program of genes involved in synaptic function upon learning in the hippocampus. Consistently, FoxO6 deficiency results in decreased dendritic spine density in hippocampal neurons in vitro and in vivo. Thus, FoxO6 may promote memory consolidation by regulating a program coordinating neuronal connectivity in the hippocampus, which could have important implications for physiological and pathological age-dependent decline in memory.
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