Unique changes in synaptic morphology following tetanization under pharmacological blockade.

Long-term potentiation (LTP) in the hippocampus has been associated with changes in synaptic morphology. Whether these changes are LTP-dependent or simply a result of electrophysiological stimulation has not yet been fully determined. This study involved an examination of synaptic morphology in the rat dentate gyrus 24 h after electrophysiological stimulation sufficient to induce LTP. In one group, ketamine, a competitive NMDA antagonist, was injected prior to stimulation to block the formation of LTP. Synaptic morphological quantification included estimating the total number of synapses per neuron, determining synaptic curvature and the presence of synaptic perforations, and measuring the maximal PSD profile length of the synapses. The results indicated that most of the changes observed following the induction of LTP (increases in the proportion of concave-shaped synapses, increases in perforated concave synapses, and a decrease in the length of nonperforated concave synapses) are not observed under ketamine blockade, suggesting that they are LTP-specific and not simply the result of tetanic stimulation. Ketamine was associated, however, with several novel structural changes including a decrease in the length of the perforations in the concave perforated synapses, a reduction in the number of convex perforated synapses, and a nonlayer-specific increase in synaptic length compared to controls. Based on previous research, this combination of morphological characteristics is potentially less efficacious, which suggests that synapses that are tetanized but not potentiated, due to pharmacological blockade, appear to undergo opposing, compensatory, or homeostatic changes. These results support the suggestion that synaptic morphology changes are both stimulation- and area-specific, are highly complex, and depend on the specific local physiology.