Wnt signaling proteins act as forepersons for synapse assembly in developing animals—but they can be called out of retirement to do the same thing in adults. One key to rebooting the system is environmental enrichment, according to a study published May 28 in Neuron from the laboratory of Pico Caroni at the Friedrich Miescher Institute in Basel, Switzerland. For a mouse, that means a big cage with lots of companions, toys and hiding places, and a running wheel. For people, Caroni speculated in an e-mail to ARF, a social network, varied activities, and exercise might have similar benefits. These factors have already been linked to staving off Alzheimer disease (see ARF related news story), in which synaptic connections in the hippocampus are lost.

Caroni, first author Nadine Gogolla, who is now at Harvard University, and colleagues knew that an enriched environment enhanced the complexity of large presynaptic terminals in the hippocampus of mice (Galimberti et al., 2006). In the current work, they start to define the mechanism of the effect. Mice in the enriched environment had higher levels of Wnt7a/b in CA3 pyramidal neurons in the hippocampus than control mice housed pairwise in small, comparatively dull cages. When the scientists infused those same neurons with Wnt7 in control mice, the effect on synapse complexity mimicked that of environmental enrichment. A Wnt inhibitor quashed the increase in synaptic numbers that enriched-environment mice normally experienced.

“The findings suggest strategies to increase synaptic plasticity by enhancing Wnt signaling,” Caroni wrote. “The enhanced plasticity, if properly combined with targeted behavioral training, may be channeled to promote repair upon lesions, and possibly also after strokes.”—Amber Dance


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Paper Citations

  1. . Long-term rearrangements of hippocampal mossy fiber terminal connectivity in the adult regulated by experience. Neuron. 2006 Jun 1;50(5):749-63. PubMed.

Other Citations

  1. ARF related news story

Further Reading


  1. . Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem. 2009 Feb;16(2):147-54. PubMed.
  2. . Wnt signaling in Alzheimer's disease: up or down, that is the question. Ageing Res Rev. 2009 Apr;8(2):71-82. PubMed.
  3. . Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiol Aging. 2010 Nov;31(11):1937-49. PubMed.

Primary Papers

  1. . Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus. Neuron. 2009 May 28;62(4):510-25. PubMed.