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Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling

Nature Neuroscience volume 14, pages 1112–1114 (2011)Cite this article

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Abstract

Neurons adapt to long-lasting changes in network activity, both in vivo and in vitro, by adjusting their synaptic strengths to stabilize firing rates. We found that homeostatic scaling of excitatory synapses was impaired in hippocampal neurons derived from mice lacking presenilin 1 (Psen1−/− mice) or expressing a familial Alzheimer's disease–linked Psen1 mutation (Psen1M146V). These findings suggest that deficits in synaptic homeostasis may contribute to brain dysfunction in Alzheimer's disease.

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Figure 1: Neurons lacking PS1 do not scale up synaptic strengths in response to chronic activity blockade or inhibition of CaMKIV.
Figure 2: Psen1M146V neurons display synaptic scaling deficits that can be rescued by expression of constitutively active Akt.

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References

  1. De Strooper, B. Neuron 38, 9–12 (2003).

    Article  CAS  Google Scholar 

  2. Tanzi, R.E. & Bertram, L. Neuron 32, 181–184 (2001).

    Article  CAS  Google Scholar 

  3. LaFerla, F.M. Nat. Rev. Neurosci. 3, 862–872 (2002).

    Article  CAS  Google Scholar 

  4. Bezprozvanny, I. & Mattson, M.P. Trends Neurosci. 31, 454–463 (2008).

    Article  CAS  Google Scholar 

  5. Turrigiano, G.G. Cell 135, 422–435 (2008).

    Article  CAS  Google Scholar 

  6. Pozo, K. & Goda, Y. Neuron 66, 337–351 (2010).

    Article  CAS  Google Scholar 

  7. Ibata, K., Sun, Q. & Turrigiano, G.G. Neuron 57, 819–826 (2008).

    Article  CAS  Google Scholar 

  8. Goold, C.P. & Nicoll, R.A. Neuron 68, 512–528 (2010).

    Article  CAS  Google Scholar 

  9. Guo, Q. et al. Nat. Med. 5, 101–106 (1999).

    Article  CAS  Google Scholar 

  10. Baki, L. et al. J. Neurosci. 28, 483–490 (2008).

    Article  CAS  Google Scholar 

  11. Baki, L. et al. EMBO J. 23, 2586–2596 (2004).

    Article  CAS  Google Scholar 

  12. Kang, D.E. et al. J. Biol. Chem. 280, 31537–31547 (2005).

    Article  CAS  Google Scholar 

  13. Hou, Q., Zhang, D., Jarzylo, L., Huganir, R.L. & Man, H.Y. Proc. Natl. Acad. Sci. USA 105, 775–780 (2008).

    Article  CAS  Google Scholar 

  14. Qin, Y. et al. Genes Dev. 19, 2000–2015 (2005).

    Article  CAS  Google Scholar 

  15. Hyman, B.T. Nat. Neurosci. 14, 5–6 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank R.M. Ahlquist and N. Li for excellent technical assistance and R.L. Neve for generously providing the viral constructs. This work was supported by the American Health Assistance Foundation and the US National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS55804, J.M.S.), and the Veteran's Affairs Office of Research and Development Medical Research Service (D.G.C.).

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Author notes

  1. Kara G Pratt & Eric C Zimmerman

    Present address: Present address: Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming, USA (K.G.P.), Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (E.C.Z.).,

Authors and Affiliations

  1. Department of Physiology & Biophysics, University of Washington School of Medicine, Seattle, Washington, USA

    Kara G Pratt, Eric C Zimmerman & Jane M Sullivan

  2. Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Seattle, Washington, USA

    David G Cook

  3. Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA

    David G Cook

  4. Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington, USA

    David G Cook

Authors
  1. Kara G Pratt
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  2. Eric C Zimmerman
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  3. David G Cook
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  4. Jane M Sullivan
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Contributions

K.G.P. and J.M.S. conceived the experiments and, together with E.C.Z., carried them out and analyzed the data. D.G.C. provided critical reagents. All of the authors contributed to writing the paper.

Corresponding author

Correspondence to Jane M Sullivan.

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The authors declare no competing financial interests.

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Pratt, K., Zimmerman, E., Cook, D. et al. Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling. Nat Neurosci 14, 1112–1114 (2011). https://doi.org/10.1038/nn.2893

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