title: Significance of synaptic Zn2+signaling in zincergic and non-zincergic synapses in the hippocampus in cognition.
abstract: A portion of zinc concentrates in the synaptic vesicles in the brain and is released from glutamatergic (zincergic) neuron terminals. It serves as a signaling factor (in a form of free Zn2+). Both extracellular Zn2+signaling, which predominantly originates in Zn2+release from zincergic neuron terminals, and intracellular Zn2+signaling, which is often linked to extracellular Zn2+signaling, are involved in hippocampus-dependent memory. At mossy fiber-CA3 pyramidal cell synapses and Schaffer collateral-CA1 pyramidal cell synapses, which are zincergic, extracellular Zn2+signaling leads to intracellular Zn2+signaling and is involved in learning and memory. At medial perforant pathway-dentate granule cell synapses, which are non-zincergic, intracellular Zn2+signaling, which originates in the internal stores containing Zn2+, is involved in learning and memory. The blockade of Zn2+signaling with Zn2+chelators induces memory deficit, while the optimal amount range of Zn2+signaling is unknown. It is possible that the degree and frequency of Zn2+signaling, which determine the increased Zn2+levels, modulates learning and memory as well as intracellular Ca2+signaling. To understand the precise role of synaptic Zn2+signaling in the hippocampus, the present paper summarizes the current knowledge on Zn2+signaling at zincergic and non-zincergic synapses in the hippocampus in cognition and involvement of zinc transporters and zinc-binding proteins in synaptic Zn2+signaling.
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Hanuna
authors.initials: H
authors.lastname: Tamano
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Koike
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakada
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yukina
authors.initials: Y
authors.lastname: Shakushi
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: takedaa@u-shizuoka-ken.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D002614:Chelating Agents / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D015032:Zinc
keywords: Hippocampus; Memory; Mossy fiber; Perforant pathway; Schaffer collateral; Zinc