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Cooperation between independent hippocampal synapses is controlled by glutamate uptake

An Erratum to this article was published on 01 May 2002

Abstract

Localized action of released neurotransmitters is the basis for synaptic independence. In the hippocampal neuropil, where synapses are densely packed, it has been postulated that released glutamate, by diffusing out of the synaptic cleft, may also activate postsynaptic receptors at neighboring synapses. Here we show that neighboring excitatory synapses on hippocampal CA1 pyramidal cells can cooperate in the activation of postsynaptic receptors through the confluence of released glutamate, and that this cooperation is controlled by glutamate uptake. Furthermore, glutamate transporters control temporal interactions between transmitter transients originating from the same axon. Thus, cooperative interactions between excitatory synapses are modulated in space and time by glutamate uptake.

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Figure 1: Confluence of synaptically released glutamate between neighboring synapses.
Figure 2: Changes in the duration of NMDAR-mediated EPSCs depend on the density of active synapses and not on the size of the EPSC.
Figure 3: Desensitization of NMDAR-mediated currents is not affected by TBOA.
Figure 4: Confluence of glutamate on NMDARs located outside the postsynaptic domain of action of individual synapses.
Figure 5: Temporal interactions between glutamate transients.
Figure 6: Time course of synaptically released glutamate in the absence of functional uptake.
Figure 7: Cooperation between independent synapses in the absence of an uptake inhibitor.

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Acknowledgements

We thank K. Shimamoto for the gift of TBOA, B. Gähwiler for the sharing of slice cultures and comments on the manuscript, C. Gee, U. Gerber and C. Heuss for comments on the manuscript, and R. Dürr, L. Heeb, H. Kasper and L. Rietschin for technical assistance. Supported by the Swiss National Science Foundation (631-057982.99).

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Correspondence to Massimo Scanziani.

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Arnth-Jensen, N., Jabaudon, D. & Scanziani, M. Cooperation between independent hippocampal synapses is controlled by glutamate uptake. Nat Neurosci 5, 325–331 (2002). https://doi.org/10.1038/nn825

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