Changes in synaptic ultrastructure during reactive synaptogenesis in the rat dentate gyrus

Advances in stereology, combined with continuing relevance to aging, as well as recovery from disease and injury make the reexamination of reactive synaptogenesis (RS) overdue. Moreover, recent mathematical models have suggested novel aspects of morphology, such as compartmentalization, may have profound effects on synaptic transmission. Given these novel findings, their correlation with other models of synaptic plasticity, and their potential significance for behavioral function, the precise nature of these changes need to be explored through quantitative morphometry. Towards this goal, the synaptic morphology of the dentate gyrus was assessed via serial electron microscopy at 3, 6, 10, 15, and 30 days following unilateral entorhinal cortex lesions. Foremost, the results showed that degree of curvature is a plastic feature of synapses. During RS, concave synapses showed an immediate/long-lasting increase in curvature, suggesting their importance in the compensation response. Flat synapses showed unique changes in growth, having implications for development and activation following synaptogenesis. Moreover, changes in size and curvature showed a different dynamic depending on proximity from damage. In the directly denervated MML, synapses showed an increase in curvature proportionate to increases in size. In the neighboring IML, however, these changes were independent-increases in curvature far surpassed synaptic growth.