Synaptic modifications at the CA3-CA1 synapse after chronic AMPA receptor blockade in rat hippocampal slices.
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.
Mateos
José María
JM
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. jose.maria.mateos@access.uzh.ch
Lüthi
Andreas
A
Savic
Natasa
N
Stierli
Beat
B
Streit
Peter
P
Gähwiler
Beat H
BH
McKinney
R Anne
RA
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline