Brain-derived neurotrophic factor transiently stabilizes silent synapses on developing neuromuscular junctions.
A general feature of the developing nervous system is the activity-dependent rearrangement of genetically defined, synaptic connections. A parallel process occurs at the developing neuromuscular junction as activity-dependent synapse withdrawal reduces the initial polyneuronal innervation of individual muscle fibers to a mononeuronal innervation within the first few weeks after birth. Because members of the neurotrophin gene family influence motor neuron differentiation and survival, we examined whether or not they also influence synaptic rearrangements in neonatal muscles. We found that treatment with brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) causes the transient retention of multiple synaptic contacts on neonatal myofibers. However, the combination of both electrophysiological and histological assays revealed that the majority of such supernumerary synaptic contacts are functionally inactive or "silent." There also occurs an increase in the number of retracting axons. Because BDNF mRNA is expressed in developing muscle and the trkB tyrosine kinase receptor for BDNF is expressed by neonatal motor neurons, our results suggest that BDNF may play an endogenous role in the refinement of synaptic connectivity that occurs in skeletal muscles after birth.
Kwon
Y W
YW
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Gurney
M E
ME
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor; D004594:Electrophysiology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D020933:Neurotrophin 3; D011247:Pregnancy; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; C073922:neurotrophin 4