title: Distinct subsets of Syt-IV/BDNF vesicles are sorted to axons versus dendrites and recruited to synapses by activity.
abstract: BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation, a phenomenon that underlies learning and memory. However, whether BDNF acts in a diffuse manner or is targeted to specific neuronal subcompartments or synaptic sites to affect circuit function remains unknown. Here, using photoactivation of BDNF or syt-IV (a regulator of exocytosis present on BDNF-containing vesicles) in transfected rat hippocampal neurons, we discovered that distinct subsets of BDNF vesicles are targeted to axons versus dendrites and are not shared between these compartments. Moreover, syt-IV- and BDNF-harboring vesicles are recruited to both presynaptic and postsynaptic sites in response to increased neuronal activity. Finally, using syt-IV knockout mouse neurons, we found that syt-IV is necessary for both presynaptic and postsynaptic scaling of synaptic strength in response to changes in network activity. These findings demonstrate that BDNF-containing vesicles can be targeted to specific sites in neurons and suggest that syt-IV-regulated BDNF secretion is subject to spatial control to regulate synaptic function in a site-specific manner.
authors.affiliation: Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53706, USA. c.dean@eni-g.de
authors.forename: Camin
authors.initials: C
authors.lastname: Dean
authors.forename: Huisheng
authors.initials: H
authors.lastname: Liu
authors.forename: Thorsten
authors.initials: T
authors.lastname: Staudt
authors.forename: Markus A
authors.initials: MA
authors.lastname: Stahlberg
authors.forename: Siv
authors.initials: S
authors.lastname: Vingill
authors.forename: Johanna
authors.initials: J
authors.lastname: Bückers
authors.forename: Dirk
authors.initials: D
authors.lastname: Kamin
authors.forename: Johann
authors.initials: J
authors.lastname: Engelhardt
authors.forename: Meyer B
authors.initials: MB
authors.lastname: Jackson
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Hell
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D003712:Dendrites / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D013572:Synaptic Vesicles / Q000145:classification* / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins / Q000172:deficiency / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018683:Excitatory Amino Acid Agents; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; C489788:MAP2 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018091:Receptors, AMPA; C492245:SLC32A1 protein, human; D026941:Sodium Channel Blockers; D016708:Synaptophysin; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D050857:Synaptotagmins; D005576:Colforsin; D013779:Tetrodotoxin; C104722:glutamate receptor ionotropic, AMPA 2; D005998:Glycine