Synaptic 5'-nucleotidase activity reflects lesion-induced sprouting within the adult rat dentate gyrus

In development, the ectoenzyme 5'-nucleotidase marks maturing cerebellar and cortical synapses, but it is localized in glial cells in the normal, adult nervous system. With a histochemical lead technique, we have now investigated its localization during reactive synaptogenesis in the dentate gyrus of adult rats deprived of entorhinal afferents. A band of enhanced 5'-nucleotidase reaction product was present in the outer portions of the dentate molecular layer between 5 and 75 days after destruction of the ipsilateral entorhinal cortex. At the ultrastructural level, 5'-nucleotidase-positive microglia and degenerating axon terminals were numerous within this band during the first postoperative week. Between Days 7 and 75, intact synapses were found that exhibited 5'-nucleotidase reaction product in their clefts. Astrocytic labeling was abundant. No enzyme-positive synapses and few labeled glial elements were present in the control molecular layer. Conspicuous 5'-nucleotidase activity within synaptic clefts of mossy fiber terminals was present between Postoperative Days 10 and 40 on the operated side, but the staining was sporadic on the control side. We conclude that 5'-nucleotidase is associated with lesion-induced synaptic remodeling in the dentate gyrus. The band of 5'-nucleotidase reaction product within the outer molecular layer corresponds to the zone where the lesioned entorhinal fibers degenerate and where other afferents sprout. Here, the transient appearance of 5'-nucleotidase within synaptic clefts parallels the time course of synaptic reinnervation. The enzyme is also indicative of the sprouting response of mossy fiber terminals. Functional properties of 5'-nucleotidase in purinergic neuromodulation and cellular adhesion may be relevant for the generation and plasticity of synaptic contacts.