PLASTICITY OF DEVELOPING NEUROMUSCULAR SYNAPSES AND MOLECULAR MECHANISMS

A Xenopus nerve-muscle culture was developed to study activity-dependent changes at developing synapses. Rapid heterosynaptic depression in polyneuronally innervated muscle cells was induced by repetitive electrical stimulation. The synaptic depression is Hebbian in nature, ie. it depends on non-coincident pre- and postsynaptic activity. Postsynaptic receptor activation and Ca2+ influx are involved in the induction of synaptic depression, but the expression of depression appears to depend on a reduction of presynaptic ACh secretion, implicating retrograde signaling. In the same culture, we also observed rapid potentiating effects of neurotrophins and caIcitonin-gene-related-peptide on the presynaptic ACh secretion and postsynaptic ACh responses, respectively. Since the secretion of neuropeptides may also be activity-dependent, a complex interplay of both electrical and chemical factors may be responsible for synaptic modulation al developing synapses.