title: Blockade of intracellular Zn2+ signaling in the dentate gyrus erases recognition memory via impairment of maintained LTP.
abstract: There is no evidence on the precise role of synaptic Zn2+ signaling on the retention and recall of recognition memory. On the basis of the findings that intracellular Zn2+ signaling in the dentate gyrus is required for object recognition, short-term memory, the present study deals with the effect of spatiotemporally blocking Zn2+ signaling in the dentate gyrus after LTP induction and learning. Three-day-maintained LTP was impaired 1 day after injection of clioquinol into the dentate gyrus, which transiently reduced intracellular Zn2+ signaling in the dentate gyrus. The irreversible impairment was rescued not only by co-injection of ZnCl2 , which ameliorated the loss of Zn2+ signaling, but also by pre-injection of Jasplakinolide, a stabilizer of F-actin, prior to clioquinol injection. Simultaneously, 3-day-old space recognition memory was impaired 1 day after injection of clioquinol into the dentate gyrus, but not by pre-injection of Jasplakinolide. Jasplakinolide also rescued both impairments of 3-day-maintained LTP and 3-day-old memory after injection of ZnAF-2DA into the dentate gyrus, which blocked intracellular Zn2+ signaling in the dentate gyrus. The present paper indicates that the blockade and/or loss of intracellular Zn2+ signaling in the dentate gyrus coincidently impair maintained LTP and recognition memory. The mechanism maintaining LTP via intracellular Zn2+ signaling in dentate granule cells, which may be involved in the formation of F-actin, may retain space recognition memory.
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Minamino
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takada
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.|Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-Ku, Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D007464:Clioquinol / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology; D004558:Electric Stimulation; D005029:Ethylenediamines / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness; D015032:Zinc / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D047630:Depsipeptides; D005029:Ethylenediamines; D011725:Pyridines; C462061:ZnAF-2; C057531:jasplakinolide; D007464:Clioquinol; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium
keywords: F-actin; LTP maintenance; Zn2+ signaling; dentate gyrus; memory retention