title: Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release.
abstract: Synaptotagmin-IV (syt-IV) is a membrane trafficking protein that influences learning and memory, but its localization and role in synaptic function remain unclear. We found that syt-IV localized to brain-derived neurotrophic factor (BDNF)-containing vesicles in hippocampal neurons. Syt-IV/BDNF-harboring vesicles underwent exocytosis in both axons and dendrites, and syt-IV inhibited BDNF release at both sites. Knockout of syt-IV increased, and overexpression decreased, the rate of synaptic vesicle exocytosis from presynaptic terminals indirectly via changes in postsynaptic release of BDNF. Thus, postsynaptic syt-IV regulates the trans-synaptic action of BDNF to control presynaptic vesicle dynamics. Furthermore, selective loss of presynaptic syt-IV increased spontaneous quantal release, whereas a loss of postsynaptic syt-IV increased quantal amplitude. Finally, syt-IV knockout mice showed enhanced long-term potentiation (LTP), which depended entirely on disinhibition of BDNF release. Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP.
authors.affiliation: Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Camin
authors.initials: C
authors.lastname: Dean
authors.forename: Huisheng
authors.initials: H
authors.lastname: Liu
authors.forename: F Mark
authors.initials: FM
authors.lastname: Dunning
authors.forename: Payne Y
authors.initials: PY
authors.lastname: Chang
authors.forename: Meyer B
authors.initials: MB
authors.lastname: Jackson
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D055366:Synaptic Potentials / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018377:Neurotransmitter Agents; D050857:Synaptotagmins