Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling

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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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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.).

Author information

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.

Correspondence to Jane M Sullivan.

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The authors declare no competing financial interests.

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