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Brain-derived neurotrophic factor transiently stabilizes silent synapses on developing neuromuscular junctions
1Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Journal of Neurobiology
|April 1, 1996
Summary
Neurotrophins like brain-derived neurotrophic factor (BDNF) transiently maintain multiple synapses on neonatal muscles. However, most are silent, suggesting BDNF aids in refining neuromuscular connections after birth.
Area of Science:
- Neuroscience
- Developmental Biology
- Muscle Physiology
Background:
- Developing nervous systems undergo activity-dependent synaptic rearrangement.
- Neuromuscular junctions initially have multiple innervations per muscle fiber, which are later refined to single innervation.
Purpose of the Study:
- To investigate the role of neurotrophins in synaptic rearrangement at developing neuromuscular junctions.
- To determine if neurotrophins influence the withdrawal of supernumerary synaptic contacts in neonatal muscles.
Main Methods:
- Treatment of neonatal muscles with specific neurotrophins (BDNF, NT-3, NT-4/5).
- Electrophysiological and histological assays to assess synaptic activity and structure.
- Analysis of gene and receptor expression (BDNF mRNA, trkB receptor).
Main Results:
- Neurotrophin treatment resulted in transient retention of multiple synaptic contacts on muscle fibers.
- The majority of these extra synapses were functionally inactive ('silent').
- An increased number of retracting axons were observed following neurotrophin treatment.
Conclusions:
- BDNF, expressed in developing muscle, and its receptor trkB, expressed by motor neurons, suggest an endogenous role for BDNF.
- BDNF may actively contribute to the refinement of synaptic connectivity in skeletal muscles postnatally.
- Neurotrophins influence the elimination of less functional synaptic connections during development.