Activity-dependent regulation of synaptic clustering in a hippocampal culture system

Currently, there is a limited understanding of the factors that influence t he localization and density of individual synapses in the central nervous s ystem. Here we have studied the effects of activity on synapse formation be tween hippocampal dentate granule cells and CA3 pyramidal neurons in cultur e, taking advantage of FM1-43 as a fluorescent marker of synaptic boutons, We observed an early tendency for synapses to group together, quickly follo wed by the appearance of synaptic clusters on dendritic processes. These ev ents were strongly influenced by N-methyl-D-aspartic: acid receptor- and cy clic AMP-dependent signaling, The microstructure and localization of the sy naptic clusters resembled that found in hippocampus, at mossy fiber synapse s of stratum lucidum, Activity-dependent clustering of synapses represents a means for synaptic: targeting that might contribute to synaptic organizat ion in the brain.