Published online 3 February 2009 | Nature | doi:10.1038/news.2009.76
Corrected online: 5 February 2009

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Inheriting memory

Mothers that have led rich lives may have offspring with longer memories.

Cerebral cortex cellsThe offspring of environmentally enriched mice performed better in memory tests.Punchstock

A mother's early experiences in life may shape the memories of her children.

Researchers in the United States have shown that genetically induced memory defects in mice can be reversed by providing the mice with a stimulating environment. And what's more, female mice seem to pass these benefits on to their offspring without any changes to the DNA sequence responsible for the defect1.

Biochemist Larry Feig from Tufts University School of Medicine in Boston, Massachusetts, and leader of the group, says that if their results can be repeated in humans, "it really suggests that the effectiveness of one's memory can be influenced by the environmental stimulation experienced by the mother in her youth".

Emma Whitelaw, who studies mammalian gene expression at the Queensland Institute of Medical Research in Australia, says that the differences between human and mouse neurobiology may confound such simple translation. Still, she says the finding is "fascinating", because it suggests that an interesting trait can be passed on down through the generations without changes to gene sequence.

"What is really nice about this study," she adds, "is that it is moving to behavioural phenotypes and the brain's ability to remember and think, and I think that is powerful".

Stimulating the brain

The team came to the finding through a circuitous path. Feig's group had originally been studying cancer genes when they created a knockout mouse that had deficits in long-term potentiation, a strengthening of neuronal connections that seems to be related to memory formation. As lab animals that are given more opportunity to explore, socialize and exercise are known to develop stronger neuronal connections and better memory, Shaomin Li, Feig's postdoc at the time, decided to see whether such environmental enrichment would have any effect on the knockouts.

In 2006, the researchers showed that 14-day-old knockout mice that were exposed to enriched environments for two weeks did indeed show much higher long term potentiation than those raised in conventional cages, and that this improvement lasted for several months. The 'enriched' mice also performed about as well as normal mice in a fear-conditioning test of their memory — tending to freeze with fear when returned to a cage where they had formerly received a mild electric shock.

Furthermore, the improvements seemed to be due to the activation of a biochemical pathway that assists in long-term potentiation and masks the effect of the knocked-out gene2.

In the current study, published today in the Journal of Neuroscience1, the researchers looked at the offspring of such environmentally enriched knockout mice. They found that the offspring have activity in this same pathway. Like their parents, they have higher long term potentiation and do better in fear-conditioning tests than their brethren born to unenriched females. Enriched fathers impart no benefits.

Thanks for the memories

The mental boost for mice born to enriched females wanes after about two months, and their subsequent offspring gain no such memory improvements. Although the mechanism by which the mice pass on their smarts is unclear, Feig speculates that enrichment produces a hormonal change in the mice that persists into adulthood and affects the offspring in utero, activating the auxiliary pathway for memory formation in their developing brains.

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Whitelaw agrees that because the effect is short-lived it doesn't look like changes are being made to the mother's egg cells. Nevertheless, her lab and others have identified heritable traits in mice, such as chemical marks that change the way DNA is regulated, that seem to affect the germline directly and persist for multiple generations.

Such epigenetic changes — alterations that are inherited even though the DNA sequence hasn't been affected — may provide clues about the origins of traits and diseases that seem to be inherited but for which no genetic contributors can be found (see 'The case of the missing heritability'). "It really matters," says Whitelaw. "There's increasing evidence that the environment an embryo grows up in can have fairly permanent consequences." 

Corrected:

A description of the fear-conditioning test given in an earlier version of this piece was incorrect.
  • References

    1. Arai, J. A., Li, S., Hartley, D. M. & Feig, L. A. J. Neurosci. 29, 1496–1502 (2009).
    2. Li, S., Tian, X., Hartley, D. M. & Feig, L. A. Curr. Biol. 16, 2303–2313 (2006). | Article | ChemPort |
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