title: Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.
abstract: Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance.
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: A
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tempaku
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tamano
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002412:Cations / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000008:administration & dosage; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000378:metabolism; D017551:Microdialysis; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000008:administration & dosage; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D015032:Zinc / Q000378:metabolism*; D017967:Zinc Compounds / Q000008:administration & dosage
chemical_list: D002412:Cations; D002614:Chelating Agents; D002712:Chlorides; D011619:Psychotropic Drugs; D017967:Zinc Compounds; C016837:zinc chloride; D015032:Zinc
keywords: CA1 pyramidal cell; LTP; Schaffer collateral; Zn(2+) signaling; cognition; hippocampus