Sequential changes in synaptic structure following long-term potentiation in the rat dentate gyrus

grantor: University of TorontoLong-term potentiation (LTP) continues to be one of the most compelling models of learning and memory. While LTP has been shown to be associated with changes in synaptic morphology, the nature of these changes over the electrophysiological time course of the enhanced response, has not been determined. The current research involved a detailed electronmicroscopic examination of synaptic structure in the rat dentate gyrus at various time points following the induction of LTP. The total number of synapses per neuron, synaptic curvature, the proportion of perforated synapses, and the maximum length of synapses were examined. No overall change in the number of synapses per neuron was observed in the LTP tissue at any of the time intervals. At 24 h, however, the 'degree ' of LTP expressed was associated with the number of synapses per neuron. In the LTP animals, the proportion of irregular shaped synapses was increased at 1 h, concave shaped synapses were increased at 24 h (not apparent under pharmacological blockade), and no overall changes in shape were observed at 5 days. The proportion of perforated synapses was increased at 1 h but did not differ from controls at later time periods. The increase in perforated synapses at 1 h was particularly apparent in the proportion of concave perforated synapses and these concave perforated synapses were also more prevalent at 24 h and 5 days. Synapses were larger overall at 1 h and 5 days but not different at 24 h. These differences in length were particularly evident in concave shaped synapses which were longer at 1 h, shorter at 24 h (no change under pharmacological blockade), and longer at 5 days. Stimulated synapses appear to initially lengthen and become more perforated (1 h), then become more concave in shape and divide or form new smaller concave synapses (24 h). Finally, synapses appear to grow in length and a higher proportion of concave perforated synapses is maintained (5 days). These results describe a sequence of changes in synaptic morphology that accompany and may support the neural plasticity that underlies LTP in a structure that is associated with learning and memory.Ph.D