Suppression of Sprouting: An Early Function of NMDA Receptors in the Absence of AMPA/Kainate Receptor Activity

摘要

Electrophysiological studies have documented the existence of synapses showing only NMDA ionotropic glutamate receptor function that are therefore presumably “silent” at resting membrane potentials. Silent synapses are more prevalent in young than in older neurons, and NMDA receptor activity at such contacts may facilitate the appearance of functional AMPA receptors. However, it is uncertain whether such silent synapses actually have a function in young neurons independent of AMPA receptor induction. Using a newly characterized culture system for neurons 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 contacted but not in isolated neurons. Blocking AMPA/KA receptors or Na⁺-dependent action potentials does not mimic this effect. Moreover, in these young neurons, NMDA receptor-dependent Ca²⁺ responses to glutamate measured with confocal fluo-3 imaging are retained during AMPA/KA receptor blockade. The data suggest that many of the young contacts in these cultures are active even though they use only NMDA ionotropic glutamate receptors. Calcium influx through the NMDA receptor at these contacts seems to reduce neurite motility. This effect should lead to the accumulation of glutamatergic inputs on NMDA receptor-expressing dendrites, which could facilitate the onset of AMPA/KA receptor function and the action potential-dependent phase of synaptogenesis.