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Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus

  1. J. Z. Kiss‡
  1. *Neuropharmacology and Department of ‡Morphology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland; and §Laboratoire de Génétique et Physiologie du Développement, Centre National de la Recherche Scientifique 9943, Parc Scientifique de Luminy, 13288 Marseille, France

  1. Communicated by Hans Thoenen, Max Planck Institute of Neurobiology, Martinsried, Germany (received for review October 20, 1999)

Abstract

The neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) contribute to long-term potentiation (LTP) in the CA1 hippocampus. Here we report that the deficient LTP found in slices prepared from NCAM knockout mice and in organotypic slice cultures treated with Endo-N, an enzyme that cleaves the PSA moiety of NCAM, can be rescued by brain-derived neurotrophic factor (BDNF). This effect is not reproduced by nerve growth factor, but can be obtained with high concentrations of NT4/5. The effect of BDNF cannot be accounted for by modifications of N-methyl-d-aspartate receptor-dependent responses or of high-frequency bursts. PSA-NCAM, however, could directly interact with BDNF. Exogenous application of PSA residues or recombinant PSA-NCAM also prevents LTP. Furthermore trkB phosphorylation, and thus BDNF signaling, is reduced in both NCAM knockout mice and Endo-N-treated slice cultures. These results suggest that one action of PSA-NCAM could be to sensitize pyramidal neurons to BDNF, thereby modulating activity-dependent synaptic plasticity.

Footnotes

    • ↵† To whom reprint requests should be addressed. E-mail: Dominique.Muller{at}medecine.unige.ch.

  • Abbreviations

    NCAM,
    neural cell adhesion molecule;
    BDNF,
    brain-derived neurotrophic factor;
    PSA,
    polysialic acid;
    LTP,
    long-term potentiation;
    TBS,
    theta burst stimulation;
    EPSP,
    excitatory postsynaptic potential;
    NGF,
    nerve growth factor;
    NMDA,
    N-methyl-d-aspartate
    • Received October 20, 1999.
    • Accepted January 19, 2000.

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