J. M. Mateos and A. Lüthi contributed equally to this work.
Synaptic modifications at the CA3–CA1 synapse after chronic AMPA receptor blockade in rat hippocampal slices
Article first published online: 4 MAY 2007
The Journal of Physiology
Volume 581, Issue 1, pages 129–138, May 2007
How to Cite
Mateos, J. M., Lüthi, A., Savic, N., Stierli, B., Streit, P., Gähwiler, B. H. and McKinney, R. A. (2007), Synaptic modifications at the CA3–CA1 synapse after chronic AMPA receptor blockade in rat hippocampal slices. The Journal of Physiology, 581: 129–138. doi: 10.1113/jphysiol.2006.120550
- Issue published online: 4 MAY 2007
- Article first published online: 4 MAY 2007
- (Received 6 September 2006; accepted after revision 13 February 2007; first published online 15 February 2007)
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.