MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

  1. Karl Obrietan1,4
  1. 1Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA
  2. 2Department of Pharmaceutical Science & Technology, Catholic University of Daegu, Gyeongbuk, Republic of Korea, 712-702
  3. 3MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom

    Abstract

    Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1−/− mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1−/− mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1−/− mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1−/− animals. MSK1−/− mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

    Footnotes

    • 4 Corresponding author

      E-mail obrietan.1{at}osu.edu

    • [Supplemental material is available for this article.]

    • Received January 24, 2012.
    • Accepted July 29, 2012.
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