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NMDA receptor activation limits the number of synaptic connections during hippocampal development

Nature Neuroscience volume 4, pages 1102–1107 (2001)Cite this article

Abstract

Activity-dependent synaptic plasticity triggered by N-methyl-d-aspartate (NMDA) receptor activation is a fundamental property of many glutamatergic synapses and may be critical for the shaping and refinement of the structural and functional properties of neuronal circuits during early postnatal development. Using a combined morphological and electrophysiological approach, we showed that chronic blockade of NMDA receptors in hippocampal slice cultures during the first two weeks of postnatal development leads to a substantial increase in synapse number and results in a more complex dendritic arborization of CA1 pyramidal cells. Thus, the development of excitatory circuitry in the hippocampus is determined by two opposing processes: NMDA receptor-independent synapse formation and NMDA receptor-dependent attenuation of synaptogenesis.

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Figure 1: Chronic NMDA receptor blockade leads to an increase in mEPSC frequency in CA1 pyramidal cells.
Figure 2: The probability of release is not increased in CPP-treated slices.
Figure 3: Chronic NMDA receptor blockade does not affect the AMPA/NMDA ratio of evoked and miniature EPSCs.
Figure 4: Chronic NMDA receptor blockade increases the density of putative presynaptic boutons.
Figure 5: Chronic NMDA receptor blockade increases the complexity of dendritic arborization.
Figure 6: Effects of chronic NMDA receptor blockade on dendritic spines.

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Acknowledgements

We thank L. Heeb, L. Rietschin and R. Schöb for technical assistance and U. Gerber, P. Streit and M. Scanziani for discussions and for reading the manuscript. Supported by Norvatis Pharma Ltd., the Basque Government, and the Dr Eric Slack-Gyr and Swiss National Science (31-41829.94) Foundations.

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  1. Andreas Lüthi

    Present address: Department of Pharmacology/Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056, Basel, Switzerland

Authors and Affiliations

  1. Brain Research Institute, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland

    Andreas Lüthi, Lucia Schwyzer, José María Mateos, Beat H. Gähwiler & R. Anne McKinney

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Correspondence to R. Anne McKinney.

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Lüthi, A., Schwyzer, L., Mateos, J. et al. NMDA receptor activation limits the number of synaptic connections during hippocampal development. Nat Neurosci 4, 1102–1107 (2001). https://doi.org/10.1038/nn744

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