SUPPRESSION OF SPROUTING - AN EARLY FUNCTION OF NMDA RECEPTORS IN THEABSENCE OF AMPA KAINATE RECEPTOR ACTIVITY/

Electrophysiological studies have documented the existence of synapses showing only NMDA ionotropic glutamate receptor function that are the refore presumably ''silent'' at resting membrane potentials. Silent sy napses are more prevalent in young than in older neurons, and NMDA rec eptor activity at such contacts may facilitate the appearance of funct ional AMPA receptors. However, it is uncertain whether such silent syn apses actually have a function in young neurons independent of AMPA re ceptor induction. Using a newly characterized culture system for neuro ns from larval Xenopus tecta, we show that blocking NMDA receptors or preventing changes in intracellular free Ca2+ concentration with BAPTA AM significantly increases neurite sprouting and elongation in contac ted but not in isolated neurons. Blocking AMPA/KA receptors or Na+-dep endent action potentials does not mimic this effect. Moreover, in thes e young neurons, NMDA receptor-dependent Ca2+ responses to glutamate m easured with confocal fluo-3 imaging are retained during AMPA/KA recep tor blockade. The data suggest that many of the young contacts in thes e cultures are active even though they use only NMDA ionotropic glutam ate receptors. Calcium influx through the NMDA receptor at these conta cts seems to reduce neurite motility. This effect should lead to the a ccumulation of glutamatergic inputs on NMDA receptor-expressing dendri tes, which could facilitate the onset of AMPA/KA receptor function and the action potential-dependent phase of synaptogenesis.