[Spatial distribution of synaptic vesicles in CA1 hippocampal synapses under conditions of induced long-term...

Prolonged activation of excitatory glutamatergic synapses causes modifications in their functioning and ultrastructural organization. While postsynaptic activity-induced changes have been relatively well studied, the data on spatial dynamics of synaptic vesicles (SV) under conditions of synaptic activation are still lacking. Using organotypic hippocampal slice cultures as a model system and electron microscopy as a technique, we analyzed changes in SV numbers and their spatial distribution in spine synapses ofhippocampal CA1 area. Two approaches were used to activate synapses: a protocol of brief oxygen-glucose deprivation known to induce so-called anoxia-hypoglycemic long-term potentiation (LTP), as well as high frequency stimulation of Schaffer collaterals inducing LTP of evoked postsynaptic potentials in CA1 synapses. Observations during the first hour after stimulation (30 and 60 min time-points) have shown that in both cases active functioning of synapses leaded to decrease in the total SV number as well as to depletion of the readily releasable SV pool. Both experimental protocols caused a decrease in spatial clustering of SV which was more pronounced after anoxia-hypoglycemic LTP. Possible mechanisms and functional consequences of these phenomena are discussed.