Synaptic interface surface area increases with long-term potentiation in the hippocampal dentate gyrus.

The present study continues our attempt to understand the ultrastructural changes that accompany and may underlie long-term potentiation (LTP). This report describes changes with LTP in the surface area of the pre- and postsynaptic membrane apposition at the synapses formed by entorhinal cortical (EC) axons with granule cell dendritic spines of the dentate gyrus (DG). The electrophysiology and electron microscopy of the DGs from each animal followed conventional procedures. The trace length of the pre- and postsynaptic apposition was measured for identified asymmetric synapses in the dentate molecular layer. The total apposed membrane surface area per unit volume (Sv) was then computed for 4 categories of synaptic profiles for each third of the molecular layer. Statistical analysis of the Sv data used multivariate analyses of variance. Across the entire molecular layer, total apposed Sv does not change significantly with LTP. However, in the activated portion of the molecular layer, total apposed Sv increases significantly, reflecting a significant increase in the apposed Sv for the concave spine profiles there. For these spine profiles, the increased apposed Sv is due to the increased membrane area both at the postsynaptic density and beyond. The average apposed surface area per individual synapse also increases markedly with LTP. The present data support the hypothesis of coordinated pre- and postsynaptic anatomical changes with LTP in the EC-DG system.