Induction of mossy fiber --> Ca3 long-term potentiation requires translocation of synaptically released Zn2+.
The mammalian CNS contains an abundance of chelatable Zn(2+) 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 Zn(2+) release from mossy fiber synaptic terminals and subsequent entry into postsynaptic neurons has prompted us to investigate the role of synaptically released Zn(2+) in the induction of long-term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of synaptically released Zn(2+) with the membrane-impermeable Zn(2+) chelator CaEDTA (10 mm) blocked induction of NMDA receptor-independent mossy fiber LTP by high-frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking Zn(2+) release by bath application of Zn(2+) (50-100 microm) without HFS induced a long-lasting potentiation of synaptic transmission that lasted more than 3 hr. Moreover, our experiments indicate the effects of Zn(2+) 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 Zn(2+) entry into postsynaptic neurons. These results indicate that synaptically released Zn(2+), acting as a second messenger, is necessary for the induction of LTP at mossy fiber-->CA3 synapses of hippocampus.
Li
Y
Y
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Hough
C J
CJ
Frederickson
C J
CJ
Sarvey
J M
JM
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D002614:Chelating Agents; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D018698:Glutamic Acid; D004492:Edetic Acid; D015032:Zinc