Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse

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...

Full description

Bibliographic Details
Main Authors: Pan, Enhui, Zhang, Xiao-an, Huang, Zhen, Krezel, Artur, Zhao, Min, Tinberg, Christine E., Lippard, Stephen J., McNamara, James O.
Other Authors: Massachusetts Institute of Technology. Department of Chemistry
Format: Article
Language:en_US
Published: Elsevier 2015
Online Access:http://hdl.handle.net/1721.1/95813
https://orcid.org/0000-0002-2693-4982
_version_ 1811089358144405504
author Pan, Enhui
Zhang, Xiao-an
Huang, Zhen
Krezel, Artur
Zhao, Min
Tinberg, Christine E.
Lippard, Stephen J.
McNamara, James O.
author2 Massachusetts Institute of Technology. Department of Chemistry
author_facet Massachusetts Institute of Technology. Department of Chemistry
Pan, Enhui
Zhang, Xiao-an
Huang, Zhen
Krezel, Artur
Zhao, Min
Tinberg, Christine E.
Lippard, Stephen J.
McNamara, James O.
author_sort Pan, Enhui
collection MIT
description 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.
first_indexed 2024-09-23T14:17:54Z
format Article
id mit-1721.1/95813
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T14:17:54Z
publishDate 2015
publisher Elsevier
record_format dspace
spelling mit-1721.1/958132022-09-28T19:49:01Z Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse Pan, Enhui Zhang, Xiao-an Huang, Zhen Krezel, Artur Zhao, Min Tinberg, Christine E. Lippard, Stephen J. McNamara, James O. Massachusetts Institute of Technology. Department of Chemistry Zhang, Xiao-an Huang, Zhen Zhao, Min Tinberg, Christine E. Lippard, Stephen J. 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. National Institute of General Medical Sciences (U.S.) (Grant GM065519) 2015-03-04T19:26:10Z 2015-03-04T19:26:10Z 2011-09 2011-07 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/95813 Pan, Enhui, Xiao-an Zhang, Zhen Huang, Artur Krezel, Min Zhao, Christine E. Tinberg, Stephen J. Lippard, and James O. McNamara. “Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse.” Neuron 71, no. 6 (September 2011): 1116–1126. © 2011 Elsevier Inc. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1016/j.neuron.2011.07.019 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle Pan, Enhui
Zhang, Xiao-an
Huang, Zhen
Krezel, Artur
Zhao, Min
Tinberg, Christine E.
Lippard, Stephen J.
McNamara, James O.
Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title_full Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title_fullStr Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title_full_unstemmed Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title_short Vesicular Zinc Promotes Presynaptic and Inhibits Postsynaptic Long-Term Potentiation of Mossy Fiber-CA3 Synapse
title_sort vesicular zinc promotes presynaptic and inhibits postsynaptic long term potentiation of mossy fiber ca3 synapse
url http://hdl.handle.net/1721.1/95813
https://orcid.org/0000-0002-2693-4982
work_keys_str_mv AT panenhui vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT zhangxiaoan vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT huangzhen vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT krezelartur vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT zhaomin vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT tinbergchristinee vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT lippardstephenj vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse
AT mcnamarajameso vesicularzincpromotespresynapticandinhibitspostsynapticlongtermpotentiationofmossyfiberca3synapse