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Neurotrophin-evoked rapid excitation through TrkB receptors

Nature volume 401, pages 918–921 (1999)Cite this article

Abstract

Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons1,2,3. They are also essential for modulating activity-dependent neuronal plasticity4,5,6,7. Here we show that neurotrophins elicit action potentials in central neurons. Even at low concentrations, brain-derived neurotrophic factor (BDNF) excited neurons in the hippocampus, cortex and cerebellum. We found that BDNF and neurotrophin-4/5 depolarized neurons just as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. Neurotrophin-3 produced much smaller responses, and nerve growth factor was ineffective. The neurotrophin-induced depolarization resulted from the activation of a sodium ion conductance which was reversibly blocked by K-252a, a protein kinase blocker which prefers tyrosine kinase Trk receptors8. Our results demonstrate a very rapid excitatory action of neurotrophins, placing them among the most potent endogenous neuro-excitants in the mammalian central nervous system described so far.

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Figure 1: Excitatory action of BDNF in central neurons.
Figure 2: Dose-dependence of BDNF-evoked neuronal firing in hippocampal CA1 pyramidal neurons.
Figure 3: TrkB requirement for the NT-mediated excitation of hippocampal CA1 pyramidal neurons.
Figure 4: Mechanism underlying the BDNF-induced inward current in hippocampal CA1 pyramidal neurons.

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Acknowledgements

We thank R. Trautmann and E. Eilers for expert technical assistance and M. Ashdown for editorial assistance. This study was supported by a fellowship from the DFG to K.W.K. and by grants from the Deutsche Forschungsgemeinschaft and the Human Frontier Science Program to A.K.

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Authors and Affiliations

  1. Institut für Physiologic, Technische Universität München, Biedersteinerstr. 29, München, 80802, Germany

    Karl W. Kafitz, Christine R. Rose & Arthur Konnerth

  2. I. Physiologisches Institut, Universität des Saarlandes, Homburg, 66421, Germany

    Karl W. Kafitz, Christine R. Rose & Arthur Konnerth

  3. Max-Plack-Institut für Neurobiologie, Am Klopferspitz 18A, Martinsried, 82152, Germany

    Hans Thoenen

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  1. Karl W. Kafitz
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  2. Christine R. Rose
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  4. Arthur Konnerth
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Correspondence to Arthur Konnerth.

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Kafitz, K., Rose, C., Thoenen, H. et al. Neurotrophin-evoked rapid excitation through TrkB receptors. Nature 401, 918–921 (1999). https://doi.org/10.1038/44847

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