A new type of lesion-induced synaptogenesis: I. Synaptic turnover in non-denervated zones of the dentate gyrus in young adult rats.

It is well established that partial denervation causes the formation of new synapses within denervated areas. It is also possible that synapse formation and remodeling occurs outside denervated zones. In this study we evaluate this possibility by examining the effect of a unilateral entorhinal lesion on the number and characteristics of synapses in non-denervated zones of the dentate gyrus within the hippocampal formation. A unilateral entorhinal lesion massively denervates the outer two-thirds of the ipsilateral dentate molecular layer and also causes a minor loss of synapses in the outer two-thirds of the contralateral dentate molecular layer. The inner one-third of the molecular layer is not denervated on either side. In the ipsilateral inner molecular layer the number of synapses rapidly decreases by about 20% and recovers by 10 days post-lesion. Similarly, in the contralateral inner molecular layer, synapses are lost and replaced, but the time course is slower. Loss is maximal at 60 days post-lesion and this recovers by 180 days post-lesion. Thus, a complete cycle of turnover occurs in both of the inner molecular layers. No degenerating terminals of any type were seen throughout the time course in these layers. Small synapses with non-complex synaptic junctions appear to account for most of the changes. Also the outer two-thirds of the contralateral molecular layer, which has lost less than 5% of its input, loses about 37% of its synapses and replaces the majority of them over time. However, the total number of synapses in the contralateral molecular layer never fully attains the value of unoperated animals. The total synaptic population reaches a value such that the ipsilateral and contralateral molecular layers are nearly equivalent. These changes, achieved through synaptic turnover, may represent a homeostatic response to nearby denervation which may facilitate restoration of bilateral function in the dentate gyrus.