Synapse restructuring associated with the maintenance phase of hippocampal long-term potentiation

Synapses in the middle molecular layer of the rat dentate gyrus were analyzed by electron microscopy during the maintenance phase of long-term potentiation (LTP). LTP was induced by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. The dentate gyrus was examined electron microscopically 13 days following the fourth stimulation. At this time point, synaptic responses were still significantly enhanced relative to baseline, although the extent of their potentiation was lower than 1 hour after the last high-frequency stimulation. Stimulated, but not potentiated, rats served as controls. Using the stereological double disector method, estimates of the number of different morphological types of synapses per postsynaptic neuron were obtained. The number of asymmetrical axodendritic synapses increased (by 28%) during LTP maintenance, whereas the number of other synaptic types was not significantly altered. Our previous work demonstrated that the induction of LTP is followed by a selective increase in the number of axospinous perforated synapses with multiple, completely partitioned, transmission zones. Thus, the induction and maintenance phases of LTP are characterized by different structural synaptic alterations. These alterations may be related to each other as indicated by another finding of the present study regarding the existence of perforated synapses that appear to be transitional between axospinous and axodendritic junctions. This suggests a model of structural synaptic plasticity associated with LTP in which some axospinous perforated synapses increase in numbers shortly after the induction of LTP and are then converted into axodendritic ones during LTP maintenance.