INVOLVEMENT OF AMYLOID PRECURSOR PROTEIN IN FUNCTIONAL SYNAPSE FORMATION IN CULTURED HIPPOCAMPAL-NEURONS

Amyloid precursor protein (APP) is known to be widely expressed in neu ronal cells, and enriched in the central and peripheral synaptic sites , Although it has been proposed that APP functions in synaptogenesis, no direct evidence has yet been reported, In this study we investigate d the involvement of PPP in functional synapse formation by monitoring spontaneous oscillations of intracellular Ca2+ concentration ([Ca2+]( i)) in cultured hippocampal neurons, As more and more neurons form syn apses with each other during the culture period, increasing numbers of neuronal cells show synchronized spontaneous oscillations of [Ca2+](i ). The number of neurons that showed synchronized spontaneous oscillat ions of [Ca2+](i) was significantly lower when cultured in the presenc e of monoclonal antibody 22C11 against the N-terminal portion of APP, Moreover, incubation with excess amounts of the secretory form of APP or the N-terminal fragment of APP also inhibited the increase in numbe r of neurons with synchronized spontaneous oscillations of [Ca2+](i), The addition of monoclonal antibody 22C11 or secretory form of APP did not, however affect MAP-2-positive neurite outgrowth, These findings suggest that APP play a role in functional synapse formation during CN S development. (C) 1998 Wiley-Liss, Inc.