Hebbian mechanisms revealed by electrical stimulation at developing rat neuromuscular junctions

Synapse competition and elimination are widespread developmental processes, first demonstrated at neonatal neuromuscular junctions. Action potential a ctivity was long shown to exert a powerful influence, but mechanisms and co ntribution relative to other factors are still not well understood. Here we show that replacement of natural motoneuronal discharge with synchronous a ctivity suppresses elimination of polyneuronal innervation of myofibers. Th is requires the simultaneous chronic conduction block (tetrodotoxin) and di stal electrical stimulation of motor axons during ectopic synaptogenesis in denervated adult soleus muscle. If in fact chronic stimulation is applied without central block of motor axons, the time course of synapse eliminatio n is as fast as in control muscles undergoing natural activity. Our finding s follow the prediction of Hebb's postulate and imply that asynchronous act ivity drives developmental synapse elimination in muscle. They further sugg est that motoneurons could become transiently synchronized during developme nt and regeneration, helping to establish the initial polyneuronal innervat ion.