title: Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse.
abstract: The presence of zinc in glutamatergic synaptic vesicles of excitatory neurons of mammalian cerebral cortex suggests that zinc might regulate plasticity of synapses formed by these neurons. Long-term potentiation (LTP) is a form of synaptic plasticity that may underlie learning and memory. We tested the hypothesis that zinc within vesicles of mossy fibers (mf) contributes to mf-LTP, a classical form of presynaptic LTP. We synthesized an extracellular zinc chelator with selectivity and kinetic properties suitable for study of the large transient of zinc in the synaptic cleft induced by mf stimulation. We found that vesicular zinc is required for presynaptic mf-LTP. Unexpectedly, vesicular zinc also inhibits a form of postsynaptic mf-LTP. Because the mf-CA3 synapse provides a major source of excitatory input to the hippocampus, regulating its efficacy by these dual actions, vesicular zinc is critical to proper function of hippocampal circuitry in health and disease.
authors.affiliation: Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Enhui
authors.initials: E
authors.lastname: Pan
authors.forename: Xiao-an
authors.initials: XA
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Artur
authors.initials: A
authors.lastname: Krezel
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Christine E
authors.initials: CE
authors.lastname: Tinberg
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: James O
authors.initials: JO
authors.lastname: McNamara
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D013425:Sulfanilic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011725:Pyridines; C491177:Slc30a3 protein, mouse; D013425:Sulfanilic Acids; C000609871:ZX1 chelating agent; D015032:Zinc