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Rab3A is essential for mossy fibre long-term potentiation in the hippocampus

Nature volume 388, pages 590–593 (1997)Cite this article

Abstract

Repetitive activation of excitatory synapses in the central nervous system results in a long-lasting increase in synaptic transmission called long-term potentiation (LTP). It is generally believed that this synaptic plasticity may underlie certain forms of learning and memory. LTP at most synapses involves the activation of the NMDA (N-methyl-d-aspartate) subtype of glutamate receptor, but LTP at hippocampal mossy fibre synapses is independent of NMDA receptors and has a component that is induced and expressed presynaptically1. It appears to be triggered by a rise in presynaptic Ca2+(refs 2, 3), and requires the activation of protein kinase A4,5,6, which leads to an increased release of glutamate3,7,8,9,10. Agreat deal is known about the biochemical steps involved in the vesicular release of transmitter11,12,13, but none of these steps has been directly implicated in long-term synaptic plasticity. Here we show that, although a variety of short-term plasticities are normal, LTP at mossy fibre synapses is abolished in mice lacking the synaptic vesicle protein Rab3A.

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Figure 1: Immunohistochemical analysis of the Rab3 proteins in hippocampus.
Figure 2: Mossy fibre synaptic inputs are normal in Rab3eficient mice.
Figure 3: Synaptic transmission in Rab3eficient mice.
Figure 4: Mossy fibre LTP is blocked in Rab3eficient mice.

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Acknowledgements

We thank H. Czerwonka for secretarial assistance. R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research. R.C.M. is a member of the Center for Neurobiology and Psychiatry, and the Center for the Neurobiology of Addiction. R.A.N. and R.C.M. are supported by grants from the NIH. T.C.S. was supported by grants from the HFJP and the W.M. Keck Foundation. R.J. was supported by a postdoctoral fellowship from DFG.

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Author notes

  1. Pablo E. Castillo

    Present address: Departamento de Fisiologia, Facultad de Medicina, Gral Flores 2125, Montevideo, Uruguay

Authors and Affiliations

  1. Departments of Cellular and Molecular Pharmacology, San Francisco, 94143, California, USA

    Pablo E. Castillo & Roger A. Nicoll

  2. Departments of Psychiatry and San Francisco, 94143, California, USA

    Thanos Tzounopoulos & Robert C. Malenka

  3. Departments of Physiology, University of California, San Francisco, 94143, California, USA

    Robert C. Malenka & Roger A. Nicoll

  4. Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, 75235, Texas, USA

    Roger Janz & Thomas C. Sdhof

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Correspondence to Roger A. Nicoll.

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Castillo, P., Janz, R., Sdhof, T. et al. Rab3A is essential for mossy fibre long-term potentiation in the hippocampus. Nature 388, 590–593 (1997). https://doi.org/10.1038/41574

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