Synaptic connections are made and broken in an activity-dependent manner in diverse regions of the nervous system. However, whether activity is strictly necessary for synapse elimination has not been resolved directly. Here we report that synaptic terminals occupying motor endplates made electrically silent by tetrodotoxin and alpha-bungarotoxin block were frequently displaced by regenerating axons that were also both inactive and synaptically ineffective. Thus, neither evoked nor spontaneous activation of acetylcholine receptors is required for competitive reoccupation of neuromuscular synaptic sites by regenerating motor axons.

Activity exerts powerful, selective effects on the organisation, stability and strength of synaptic connections in all parts of the nervous system, including neuromuscular junctions (Lohof et al. 1996;Sanes & Lichtman, 1999). For example, neonatal rat muscle fibres are innervated at single motor endplates by motor nerve terminals supplied by several motoneurones (polyneuronal innervation; ð_junctions), and a similar pattern is re-established in adult muscle after nerve injury and regeneration (Brown et al. 1976;Betz et al. 1979;Ribchester, 1988). With time, synaptic boutons and axonal inputs are progressively eliminated, eventually leaving most endplates innervated by only one motor axon (Gan & Lichtman, 1998). Progressive and disproportionate weakening of synaptic transmission, induced by differences in pre-and postsynaptic activity, has been presumed to underlie this competitive process (Ribchester & Taxt, 1983;Balice-Gordon & Lichtman, 1994;Coleman et al. 1997). However, activity may not be sufficient to induce elimination from all ð_junctions. Previous studies of paralysed neonatal or reinnervated adult muscle suggest that significant polyneuronal innervation persists once activity resumes (Hoffman, 1953;Brown et al. 1982;Barry & Ribchester, 1995). The properties that allow convergent synapses of different size and efficacy to persist at a motor endplate are unknown. Equally, it is unclear whether apparently stable, convergent synaptic inputs in reinnervated muscles may in

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