We investigated the influence of synaptically released glutamate on postsyn
aptic structure by comparing the effects of deafferentation, receptor antag
onists and blockers of glutamate release in hippocampal Slice cultures. CA1
pyramidal cell spine density and length decreased after transection of Sch
affer collaterals and after application of AMPA receptor antagonists or bot
ulinum toxin to unlesioned cultures. Loss of spines induced by lesion or by
botulinum toxin was prevented by simultaneous AMPA application. Tetrodotox
in did not affect spine density. Synaptically released glutamate thus exert
s a trophic effect on spines by acting at AMPA receptors. We conclude that
AMPA receptor activation by spontaneous vesicular glutamate release is suff
icient to maintain dendritic spines.