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The Journal of Neuroscience, February 4, 2009, 29(5):1496-1502; doi:10.1523/JNEUROSCI.5057-08.2009

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Development/Plasticity/Repair
Transgenerational Rescue of a Genetic Defect in Long-Term Potentiation and Memory Formation by Juvenile Enrichment

Junko A. Arai,1 * Shaomin Li,1 * Dean M. Hartley,2 and Larry A. Feig1

1Sackler School of Biomedical Sciences and Departments of Biochemistry and Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, and 2Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612

Correspondence should be addressed to Larry A. Feig at the above address. Email: larry.feig{at}tufts.edu

The idea that qualities acquired from experience can be transmitted to future offspring has long been considered incompatible with current understanding of genetics. However, the recent documentation of non-Mendelian transgenerational inheritance makes such a "Lamarckian"-like phenomenon more plausible. Here, we demonstrate that exposure of 15-d-old mice to 2 weeks of an enriched environment (EE), that includes exposure to novel objects, elevated social interactions and voluntary exercise, enhances long-term potentiation (LTP) not only in these enriched mice but also in their future offspring through early adolescence, even if the offspring never experience EE. In both generations, LTP induction is augmented by a newly appearing cAMP/p38 MAP kinase-dependent signaling cascade. Strikingly, defective LTP and contextual fear conditioning memory normally associated with ras-grf knock-out mice are both masked in the offspring of enriched mutant parents. The transgenerational transmission of this effect occurs from the enriched mother to her offspring during embryogenesis. If a similar phenomenon occurs in humans, the effectiveness of one's memory during adolescence, particularly in those with defective cell signaling mechanisms that control memory, can be influenced by environmental stimulation experienced by one's mother during her youth.

Key words: synaptic plasticity; LTP; kinase; environmental; fear; memory formation

Received Oct. 17, 2008; revised Dec. 14, 2008; accepted Dec. 16, 2008.

Correspondence should be addressed to Larry A. Feig at the above address. Email: larry.feig{at}tufts.edu






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