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J. Neurosci. 21 (20): 8015-8025

Copyright © 2001 by the Society for Neuroscience.

The Journal of Neuroscience, October 15, 2001, 21(20):8015-8025

Induction of Mossy Fiberright-arrow CA3 Long-Term Potentiation Requires Translocation of Synaptically Released Zn2+

Yang Li1, Christopher J. Hough2, Christopher J. Frederickson3, 4, and John M. Sarvey1

Departments of 1 Pharmacology and 2 Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, and 3 NeuroBioTex, Inc. and 4 Departments of Biomedical Engineering and Anatomy and Neuroscience, The University of Texas Medical Branch, Galveston, Texas 77550

The mammalian CNS contains an abundance of chelatable Zn2+ sequestered in the vesicles of glutamatergic terminals. These vesicles are particularly numerous in hippocampal mossy fiber synapses of the hilar and CA3 regions. Our recent observation of frequency-dependent Zn2+ release from mossy fiber synaptic terminals and subsequent entry into postsynaptic neurons has prompted us to investigate the role of synaptically released Zn2+ in the induction of long-term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of synaptically released Zn2+ with the membrane-impermeable Zn2+ chelator CaEDTA (10 mM) blocked induction of NMDA receptor-independent mossy fiber LTP by high-frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking Zn2+ release by bath application of Zn2+ (50-100 µM) without HFS induced a long-lasting potentiation of synaptic transmission that lasted more than 3 hr. Moreover, our experiments indicate the effects of Zn2+ were not attributable to its interaction with extracellular membrane proteins but required its entry into presynaptic or postsynaptic neurons. Co-released glutamate is also essential for induction of LTP under physiological conditions, in part because it allows Zn2+ entry into postsynaptic neurons. These results indicate that synaptically released Zn2+, acting as a second messenger, is necessary for the induction of LTP at mossy fiberright-arrowCA3 synapses of hippocampus.

Key words: zinc; long-term potentiation; CA3; hippocampus; CaEDTA; mossy fiber; plasticity; Na-pyrithione; Newport Green; synaptic transmission

Copyright © 2001 Society for Neuroscience  0270-6474/01/21208015-11$05.00/0

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