ProBDNF and Mature BDNF as Punishment and Reward Signals for Synapse Elimination at Mouse Neuromuscular Junctions

@article{Je2013ProBDNFAM,
  title={ProBDNF and Mature BDNF as Punishment and Reward Signals for Synapse Elimination at Mouse Neuromuscular Junctions},
  author={H Shawn Je and Feng Yang and Yuanyuan Ji and Srilatha Potluri and Xiu-Qing Fu and Zhen-Ge Luo and Guhan Nagappan and Jia Pei Chan and Barbara L. Hempstead and Young-Jin Son and Bai Lu},
  journal={The Journal of Neuroscience},
  year={2013},
  volume={33},
  pages={9957 - 9962}
}
During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that… 
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TLDR
The authors show that BDNF-TrkB retrograde signaling is a “punishment” signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.
Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development
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A molecular background for developmental axonal competition and loss is proposed and transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors, adenosine autoreception and trophic factor receptors are studied during the development of NMJ and in the adult.
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TLDR
Results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cP KCβI) to modulate synaptic function, and indicates that a decrease in neuromuscular activity could affect the BDNF-TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromUScular function.
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TLDR
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TLDR
It is demonstrated that proBDNF impairs GABAergic transmission by the activation of two distinct pathways: a RhoA-Rock-PTEN pathway that decreases the phosphorylation levels of GABAAR, thus affecting receptor function and triggering endocytosis and degradation of internalized receptors, and a JAK-STAT-ICER pathway leading to the repression ofGAARs synthesis.
ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses
TLDR
The data obtained suggest that there is a previously unknown mechanism for the acute suppression of spontaneous and evoked ACh release in mature motor synapses, which involves the activation of p75 receptors, ROCK and GIRK channels by BDNF prodomain and requires interaction with metabotropic purinoreceptors.
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Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity
TLDR
A RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at presynaptic site is illustrated.
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