title: FoxO6 regulates memory consolidation and synaptic function.
abstract: 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.
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Dervis A M
authors.initials: DA
authors.lastname: Salih
authors.forename: Asim J
authors.initials: AJ
authors.lastname: Rashid
authors.forename: Damien
authors.initials: D
authors.lastname: Colas
authors.forename: Luis
authors.initials: L
authors.lastname: de la Torre-Ubieta
authors.forename: Ruo P
authors.initials: RP
authors.lastname: Zhu
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Morgan
authors.forename: Evan E
authors.initials: EE
authors.lastname: Santo
authors.forename: Duygu
authors.initials: D
authors.lastname: Ucar
authors.forename: Keerthana
authors.initials: K
authors.lastname: Devarajan
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Cole
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Madison
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Shamloo
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: Azad
authors.initials: A
authors.lastname: Bonni
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
authors.forename: Anne
authors.initials: A
authors.lastname: Brunet
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C525395:Foxo6 protein, mouse; D018006:Myogenic Regulatory Factors