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This Article Full Text Full Text (PDF) All Versions of this Article: 581/1/129    most recent jphysiol.2006.120550v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mateos, J. M. Articles by McKinney, R. A. Search for Related Content PubMed PubMed Citation Articles by Mateos, J. M. Articles by McKinney, R. A. Related Collections Neuroscience

¹ Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
² Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
³ Department of Pharmacology and Therapeutics, McGill University, Promenade Sir-William-Osler, Montreal, QC, Canada H3G 1Y6

Maintenance of dendritic spines, the postsynaptic elements of most glutamatergic synapses in the central nervous system, requires continued activation of AMPA receptors. In organotypic hippocampal slice cultures, chronic blockade of AMPA receptors for 14 days induces a substantial loss of dendritic spines on CA1 pyramidal neurons. Here, using serial section electron microscopy, we show that loss of dendritic spines is paralleled by a significant reduction in synapse density. In contrast, we observed an increased number of asymmetric synapses onto the dendritic shaft, suggesting that spine retraction does not inevitably lead to synapse elimination. Functional analysis of the remaining synapses revealed that hippocampal circuitry compensates for the anatomical loss of synapses by increasing synaptic efficacy. Moreover, we found that the observed morphological and functional changes were associated with altered bidirectional synaptic plasticity. We conclude that continued activation of AMPA receptors is necessary for maintaining structure and function of central glutamatergic synapses.

(Received 6 September 2006; accepted after revision 13 February 2007; first published online 15 February 2007)
Corresponding author J. M. Mateos: Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Email: jose.maria.mateos{at}access.uzh.ch

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