NITRIC-OXIDE MEDIATES ACTIVITY-DEPENDENT SYNAPTIC SUPPRESSION AT DEVELOPING NEUROMUSCULAR SYNAPSES

TEMPORAL correlation between pre- and postsynaptic activities is an im portant mechanism that regulates synaptic connectivity during developm ent and synaptic plasticity in the adult(1-3). In developing neuromusc ular junctions, postsynaptic activity is critical in functional suppre ssion and, ultimately, elimination of the synapses(4-6). Although repe titive postsynaptic firing asynchronous to the presynaptic activity re sults in a persistent synaptic suppression(7-10), the underlying molec ular mechanism remains unknown. Here we provide evidence that nitric o xide (NO), a free radical implicated in several forms of synaptic plas ticity(11-15), may serve as a retrograde signal for activity-dependent suppression in the neuromuscular synapse. NO donors and activators of the cyclic GMP pathway suppressed spontaneous and evoked synaptic cur rents. Moreover, the synaptic suppression induced by repetitive postsy naptic depolarization was prevented by the NO-binding protein haemoglo bin and by inhibitors of NO synthase. Thus, synaptic suppression may b e triggered by NO released from a postsynaptic myocyte that fires asyn chronously to the presynaptic terminal.