EFFECTS OF GLUCOSYLCERAMIDE SYNTHASE INHIBITOR AND GANGLIOSIDE GQ1B ON SYNCHRONOUS OSCILLATIONS OF INTRACELLULAR CA2-NEURONS( IN CULTURED CORTICAL)

To evaluate the role of endogenous gangliosides in synapse formation, the glucosylceramide synthase inhibitor, o-1-phenyl-2-decanoylamino-3- morpholino-1-propanol (D-PDMP), was used to deplete glycosphingolipids (GSLs) of cultured rat cerebral cortical neurons. Synapse formation b etween the neurons was estimated by the synchronous oscillation of syn aptic activity monitored by fura-2 calcium imaging. Treatment with D-P DMP resulted in dose- and time-dependent decreases in the frequency of synchronous oscillations. When a series of gangliosides (GM3, GM1, GD 3, GD1b, GT1b, and GQ1b) was supplemented to the GSL depleted cells, o nly GQ1b was able to normalize the decreased frequency by D-PDMP. Thes e results suggest that de novo synthesis of a particular molecular spe cies of the gangliosides, GQ1b, is essential for synapse formation and synaptic activity. (C) 1996 Academic Press, Inc.