GeneSet Information

Tier III GS213200 • Expression changes in the regulation of memory consolidation and synaptic function in FoxO6 vs. wild-type mice

DESCRIPTION:

The novel object recognition test was performed on two independent cohorts of mice according to Nilsson et al. (2007). One cohort consisted of mice on the mixed C57BL/6J-129sv background, and the second cohort consisted of mice that had been backcrossed to the C57BL/6J strain for at least four generations. mRNA samples were collected from the hippocampus from FoxO6 mutant and wild-type siblings before (basal) or after novel object learning. 250 ng of total RNA was reverse-transcribed to cDNA, and cDNA was hybridized to the Mouse Gene 1.0 ST array (Affymetrix). 176 genes were up-regulated significantly following object learning in wild-type mice compared with FoxO6 mutant mice (P < 0.05 for interaction between the factors genotype and learning, two-way ANOVA; P < 0.05 for wild-type sibling basal vs. learning, one-way ANOVA).

LABEL:

FoxO6 memory/synapses

SCORE TYPE:

P-Value

DATE ADDED:

None

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Salih DA, Rashid AJ, Colas D, de la Torre-Ubieta L, Zhu RP, Morgan AA, Santo EE, Ucar D, Devarajan K, Cole CJ, Madison DV, Shamloo M, Butte AJ, Bonni A, Josselyn SA, Brunet A

TITLE:

FoxO6 regulates memory consolidation and synaptic function.

JOURNAL:

Genes &amp;amp; development Dec 2012, Vol 26, pp. 2780-801

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. PUBMED: 23222102
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Annotation Information

No sequence read archive data associated with this GeneSet.


Growth (D006128)
Social Control, Formal (D012926)
Mammals (D008322)
Family (D005190)
Family Characteristics (D005191)
RNA (D012313)
Memory (D008568)
Aging (D000375)
Mice (D051379)
Spine (D013131)
Fear (D005239)
Conditioning (Psychology) (D003213)
Adult (D000328)
RNA, Messenger (D012333)
Neurons (D009474)
Dendritic Spines (D049229)
Genotype (D005838)
Insulin (D007328)
In Vitro (D007176)
Siblings (D035781)
Viruses (D014780)
Transcription Factors (D014157)
Learning (D007858)
DNA, Complementary (D018076)
Injections (D007267)
Cognition (D003071)
Analysis of Variance (D000704)
Hippocampus (D006624)
hippocampus (MA:0000191)
no abnormal phenotype detected (MP:0002169)
aging (GO:0007568)
growth (GO:0040007)
dendritic spine (GO:0043197)
learning (GO:0007612)
memory (GO:0007613)
signaling (GO:0023052)
cognition (GO:0050890)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351