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A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission

Abstract

THE mammalian central nervous system (CNS) contains an abundance of the transition metal zinc, which is highly localized in the neuronal parenchyma1–4. Zinc is actively taken up5,6 and stored in synaptic vesicles in nerve terminals7–10, and stimulation of nerve fibre tracts that contain large amounts of zinc, such as the hippocampal mossy fibre system4, can induce its release11–13, suggesting that it may act as a neuromodulator. The known interaction of zinc with the major excitatory and inhibitory amino-acid neurotransmitter receptors in the CNS supports this notion14–16. That zinc has a role in CNS synaptic transmission, however, has so far not been shown. Here we report a physiological role for zinc in the young rat hippocampus (postnatal, P3–P14 days). Our results indicate that naturally occurring spontaneous giant depolarizing synaptic potentials (GDPs) in young CA3 pyramidal neurones, mediated by the release of GAB A (γ-aminobutyric acid)17, are induced by endogenously released zinc. These synaptic potentials are inhibited by specific zinc-chelating agents. GDPs are apparently generated by an inhibitory action of zinc on both pre- and postsynaptic GABAB receptors in the hippocampus. Our study implies that zinc modulates synaptic transmission in the immature hippocampus, a finding that may have implications for understanding benign postnatal seizures in young children suffering with acute zinc deficiency18.

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