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The Journal of Neuroscience, March 18, 2009, 29(11):3395-3403; doi:10.1523/JNEUROSCI.5352-08.2009

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Behavioral/Systems/Cognitive
Environmental Enrichment Restores Memory Functioning in Mice with Impaired IL-1 Signaling via Reinstatement of Long-Term Potentiation and Spine Size Enlargement

Inbal Goshen,¹ Avi Avital,³ Tirzah Kreisel,¹ Tamar Licht,⁴ Menahem Segal,⁵ and Raz Yirmiya¹

¹Department of Psychology, The Hebrew University, Jerusalem 91905, Israel, ²Department of Psychology and ³The Center for Psychobiological Research, The Max Stern Yezreel Valley College, Emek Yezreel 19300, Israel, ⁴Deparment of Molecular Biology, The Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel, and ⁵Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel

Correspondence should be addressed to Dr. Raz Yirmiya, Department of Psychology, The Hebrew University, Mount Scopus, Jerusalem 91905, Israel. Email: razyirmiya{at}huji.ac.il

Environmental enrichment (EE) was found to facilitate memory functioning and neural plasticity in normal and neurologically impaired animals. However, the ability of this manipulation to rescue memory and its biological substrate in animals with specific genetically based deficits in these functions has not been extensively studied. In the present study, we investigated the effects of EE in two mouse models of impaired memory functioning and plasticity. Previous research demonstrated that mice with a deletion of the receptor for the cytokine interleukin-1 (IL-1rKO), and mice with CNS-specific transgenic over-expression of the IL-1 receptor antagonist (IL-1raTG) display impaired hippocampal memory and long-term potentiation (LTP). We report here a corrective effect of EE on spatial and contextual memory in IL-1rKO and IL-1raTG mice and reveal two mechanisms for this beneficial effect: Concomitantly with their disturbed memory functioning, LTP in IL-1rKO mice that were raised in a regular environment is impaired, and their dendritic spine size is reduced. Both of these impairments were corrected by environmental enrichment. No deficiencies in neurogenesis or hippocampal BDNF and vascular endothelial growth factor secretion were found in IL-1rKO mice that were raised in a regular environment, and both of these variables were increased to a similar degree in enriched IL-1rKO and wild-type mice. These findings suggest that exposure to an enriched environment may be beneficial for individuals with impaired learning and memory related to genetic impairments of IL-1 signaling (and possibly other genetic causes), by reversing impairments in dentate gyrus LTP and spine size and by promoting neurogenesis and trophic factors secretion.

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Received Nov. 5, 2008; revised Dec. 16, 2008; accepted Dec. 30, 2008.

Correspondence should be addressed to Dr. Raz Yirmiya, Department of Psychology, The Hebrew University, Mount Scopus, Jerusalem 91905, Israel. Email: razyirmiya{at}huji.ac.il

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