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Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression

Abstract

To investigate the role of phosphatidylinositol 3 kinase (PI3 kinase) in hippocampal synaptic plasticity, we used whole-cell patch clamp recordings from rat CA1 neurons to determine the effects of PI3 kinase inhibitors on long-term depression (LTD). PI3 kinase blockade caused a loss of synapse specificity of LTD that was dependent on the co-activation of NMDA-type glutamate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), and involved release of Ca2+ from intracellular stores. These findings suggest that the synapse specificity of hippocampal LTD may not be an intrinsic property of this form of homosynaptic plasticity, but rather that it can be regulated by PI3 kinase.

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Figure 1: Blockade of PI3 kinase or PKC reveals heterosynaptic LTD at hippocampal CA1 synapses.
Figure 2: Heterosynaptic LTD depends on the co-activation of NMDARs and mGluRs, and requires intracellular Ca2+ signaling.

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References

  1. Kemp, N. & Bashir, Z.I. Prog. Neurobiol. 65, 339–365 (2001).

    Article  CAS  Google Scholar 

  2. Bliss, T.V.P. & Collingridge, G.L. Nature 361, 31–39 (1993).

    CAS  Google Scholar 

  3. Bear, M.F. Proc. Natl. Acad. Sci. USA 93, 13453–13459 (1996).

    Article  CAS  Google Scholar 

  4. Malenka, R.C. & Nicoll, R.A. Science 285, 1870–1874 (1999).

    Article  CAS  Google Scholar 

  5. Sanes, J.R. & Lichtman, J.W. Nat. Neurosci. 2, 597–604 (1999).

    Article  CAS  Google Scholar 

  6. Osborne, S.L., Meunier, F.A. & Schiavo, G. Neuron 32, 9–12 (2001).

    Article  CAS  Google Scholar 

  7. Toker, A. & Cantley, L.C. Nature 387, 673–676 (1997).

    Article  CAS  Google Scholar 

  8. Kelly, A. & Lynch, M.A. Neuropharmacology 39, 643–651 (2000).

    Article  CAS  Google Scholar 

  9. Raymond, C.R., Redman, S.J. & Crouch, M.F. Neuroscience 109, 531–536 (2002).

    Article  CAS  Google Scholar 

  10. Sanna, P.P. et al. J. Neurosci. 22, 3359–3365 (2002).

    Article  CAS  Google Scholar 

  11. Daw, M.I. et al. Neuron 28, 873–886 (2000).

    Article  CAS  Google Scholar 

  12. Vlahos, C.J., Matter, W.F., Hui, K.Y. & Brown, R.F. J. Biol. Chem. 269, 5241–5248 (1994).

    CAS  PubMed  Google Scholar 

  13. Bortolotto, Z.A. & Collingridge, G.L. Eur. J. Neurosci. 12, 4055–4062 (2000).

    Article  CAS  Google Scholar 

  14. Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M-m. & Kato, K. Nature 408, 584–588 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Eli Lilly and Company for supplying LY294002, and to W. W. Anderson for providing the 'LTP' software. This work was supported by the U.K. Wellcome Trust (S.Z. and J.T.R.I.), Medical Research Council (G.L.C.) and Biotechnology and Biological Sciences Research Council (G.L.C. and J.T.R.I.).

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Correspondence to John T.R. Isaac.

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Daw, M., Bortolotto, Z., Saulle, E. et al. Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression. Nat Neurosci 5, 835–836 (2002). https://doi.org/10.1038/nn903

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