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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Nature Neuroscience volume 4, pages 1086–1092 (2001)Cite this article

Abstract

Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure–function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.

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Figure 1: Two-photon excitation of MNI-glutamate in cultured hippocampal neurons.
Figure 2: Functional mapping of glutamate sensitivities in hippocampal neurons.
Figure 3: Functional mapping of glutamate sensitivities in hippocampal neurons.
Figure 4: Spine geometry and expression of functional AMPA receptors.
Figure 5: Correlation between spine geometry and glutamate sensitivities.
Figure 6: Non-stationary fluctuation analysis of AMPA receptors in a mushroom spine.

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Acknowledgements

We thank S. Adams for a sample of azid-1, H. Tsubokawa for helpful suggestions on hippocampal slice experiments, R. Nichols for comments on the manuscript and R. Ijuin for technical assistance. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation (JST); the Research for the Future program of the Japan Society for the Promotion of Science (JSPS); Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology; and NIH (GM53395). M.M. was a JSPS research fellow.

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Authors and Affiliations

  1. Department of Cell Physiology, National Institute for Physiological Sciences, and the Graduate University for Advanced Studies, Myodaiji, 444-8585, Okazaki, Japan

    Masanori Matsuzaki, Tomomi Nemoto & Haruo Kasai

  2. CREST, Japan Science and Technology Corporation, Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Masanori Matsuzaki, Tomomi Nemoto, Masamitsu Iino & Haruo Kasai

  3. University of Tokyo School of Medicine, Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan

    Masanori Matsuzaki, Tomomi Nemoto, Yasushi Miyashita & Masamitsu Iino

  4. Department of Pharmacology and Physiology, MCP Hahnemann University, Philadelphia, 19102, Pennsylvania, USA

    Graham C. R. Ellis-Davies

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Correspondence to Haruo Kasai.

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Matsuzaki, M., Ellis-Davies, G., Nemoto, T. et al. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4, 1086–1092 (2001). https://doi.org/10.1038/nn736

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