BDNF stabilizes synapses and maintains the structural complexity of optic axons in vivo.
Brain-derived neurotrophic factor (BDNF) modulates synaptic connectivity by increasing synapse number and by promoting activity-dependent axon arbor growth. Patterned neuronal activity is also thought to influence the morphological maturation of axonal arbors by directly influencing the stability of developing synapses. Here, we used in vivo time-lapse imaging to examine the relationship between synapse stabilization and axon branch stabilization, and to better understand the participation of BDNF in synaptogenesis. Green fluorescent protein (GFP)-tagged synaptobrevin II was used to visualize presynaptic specializations in individual DsRed2-labeled Xenopus retinal axons arborizing in the optic tectum. Neutralizing endogenous tectal BDNF with function-blocking antibodies significantly enhanced GFP-synaptobrevin cluster elimination, a response that was paralleled by enhanced branch elimination. Thus, synapse dismantling was associated with axon branch pruning when endogenous BDNF levels were reduced. To obtain a second measure of the role of BDNF during synapse stabilization, we injected recombinant BDNF in tadpoles with altered glutamate receptor transmission in the optic tectum. Tectal injection of the NMDA receptor antagonists APV or MK801 transiently induced GFP-synaptobrevin cluster dismantling, but did not significantly influence axon branch addition or elimination. BDNF treatment rescued synapses affected by NMDA receptor blockade: BDNF maintained GFP-synaptobrevin cluster density by maintaining their addition rate and rapidly inducing their stabilization. Consequently, BDNF influences synaptic connectivity in multiple ways, promoting not only the morphological maturation of axonal arbors, but also their stabilization, by a mechanism that influences both synapses and axon branches.
Hu
Bing
B
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.
Nikolakopoulou
Angeliki Maria
AM
Cohen-Cory
Susana
S
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D046529:Microscopy, Electron, Transmission; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013477:Superior Colliculi / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D050988:Vesicle-Associated Membrane Protein 2; D049452:Green Fluorescent Proteins; D016291:Dizocilpine Maleate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine