Influx of extracellular Zn2+ 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Maternal malnutrition affects brain development and probably represents a leading factor in the pathogenesis of neurological and psychiatric disorders in offspring.
“several studies showed that maternal malnutrition affects brain development and probably represents a leading factor in the pathogenesis of neurological and psychiatric disorders in an offspring [60,61,62].”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [61]
Cites
Recognition memory: What are the roles of the perirhinal cortex and hippocampus?
Brown, M. W., & Aggleton, J. P. (2001) · Nature reviews. Neuroscience · doi:10.1038/35049064 · Cited by 1,555 · see citing works
Synaptic plasticity, memory and the hippocampus: a neural network approach to causality
Neves, G., Cooke, S. F., & Bliss, T. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2303 · Cited by 1,207 · see citing works
Neurobiology of Zinc and Zinc-Containing Neurons
Frederickson, C. J. (1989) · International review of neurobiology · doi:10.1016/s0074-7742(08)60279-2 · Cited by 1,070 · see citing works
Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons
Westbrook, G. L., & Mayer, M. L. (1987) · Nature · doi:10.1038/328640a0 · Cited by 852 · see citing works
Zinc Selectively Blocks the Action of N -Methyl-D-Aspartate on Cortical Neurons
Peters, S., Koh, J., & Choi, D. W. (1987) · Science · doi:10.1126/science.2883728 · Cited by 667 · see citing works
The Actions of Synaptically Released Zinc at Hippocampal Mossy Fiber Synapses
Vogt, K. E., Mellor, J. R., Tong, G., & Nicoll, R. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81149-6 · Cited by 491 · see citing works
Measurement of Intracellular Free Zinc in Living Cortical Neurons: Routes of Entry
Sensi, S. L., Canzoniero, L. M. T., Yu, S. P., Ying, H. S.-C., Koh, J., Kerchner, G. A., & Choi, D. W. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-24-09554.1997 · Cited by 465 · see citing works
Li, Y. V., Hough, C., Frederickson, C., & Sarvey, J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08015.2001 · Cited by 284 · see citing works
Ueno, S., Tsukamoto, M., Hirano, T., Kikuchi, K., Yamada, M. K., Nishiyama, N., Nagano, T., Matsuki, N., & Ikegaya, Y. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200204066 · Cited by 236 · see citing works
Frederickson, C. J., Giblin, L. J., Krężel, A., McAdoo, D. J., Muelle, R. N., Zeng, Y., Balaji, R. V., Masalha, R., Thompson, R. B., Fierke, C. A., et al. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2005.08.030 · Cited by 230 · see citing works
Insights into Zn2+ homeostasis in neurons from experimental and modeling studies
Colvin, R. A., Bush, A. I., Volitakis, I., Fontaine, C. P., Thomas, D. G., Kikuchi, K., & Holmes, W. R. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00541.2007 · Cited by 188 · see citing works
Pan, E., Zhang, X., Huang, Z., Krężel, A., Zhao, M., Tinberg, C. E., Lippard, S. J., & McNamara, J. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.019 · Cited by 187 · see citing works
Redefining the Role of Metallothionein within the Injured Brain
Chung, R. S., Penkowa, M., Dittmann, J., King, C., Bartlett, C. A., Asmussen, J. W., Hidalgo, J., Carrasco, J., Leung, Y. K., Walker, A. K., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708446200 · Cited by 153 · see citing works
Zinc Modulates Bidirectional Hippocampal Plasticity by Effects on NMDA Receptors
Izumi, Y., Auberson, Y. P., & Zorumski, C. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1258-06.2006 · Cited by 152 · see citing works
de Lima, M. N., Luft, T., Roesler, R., & Schröder, N. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.06.044 · Cited by 113 · see citing works
Sindreu, C. B. (2003) · Cerebral Cortex · doi:10.1093/cercor/13.8.823 · Cited by 103 · see citing works
Malleret, G., Alarcón, J. M., Martel, G., Takizawa, S., Vronskaya, S., Yin, D., Chen, I. Z., Kandel, E. R., & Shumyatsky, G. P. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1330-09.2010 · Cited by 101 · see citing works
A role for extracellular metallothioneins in CNS injury and repair
Chung, R. S., & West, A. K. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.10.019 · Cited by 92 · see citing works
Synaptic Zn2+ homeostasis and its significance
Takeda, A., Nakamura, M., Fujii, H., & Tamano, H. (2013) · Metallomics · doi:10.1039/c3mt20269k · Cited by 79 · see citing works
Self-citationZinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression
Takeda, A. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8158-9 · Cited by 73 · see citing works
Self-citationSpatial and memory circuits in the medial entorhinal cortex
Sasaki, T., Leutgeb, S., & Leutgeb, J. K. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.10.008 · Cited by 73 · see citing works
Takeda, A., Fuke, S., Ando, M., & Oku, N. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.009 · Cited by 65 · see citing works
Self-citationZinc enhances long-term potentiation through P2X receptor modulation in the hippocampal CA1 region
Lorca, R. A., Rozas, C., Loyola, S., Moreira‐Ramos, S., Zeise, M. L., Kirkwood, A., Huidobro-Toro, J. P., & Morales, B. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07589.x · Cited by 48 · see citing works
Transient Increase in Zn2+ in Hippocampal CA1 Pyramidal Neurons Causes Reversible Memory Deficit
Takeda, A., Takada, S., Nakamura, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028615 · Cited by 46 · see citing works
Self-citationZinc and Zolpidem Modulate mIPSCs in Rat Neocortical Pyramidal Neurons
DeFazio, T., & Hablitz, J. J. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.80.4.1670 · Cited by 46 · see citing works
Intracellular Zn2+ signaling in the dentate gyrus is required for object recognition memory
Takeda, A., Tamano, H., Ogawa, T., et al. (2014) · Hippocampus · doi:10.1002/hipo.22322 · Cited by 37 · see citing works
Self-citationNegative modulation of presynaptic activity by zinc released from schaffer collaterals
Takeda, A., Fuke, S., Tsutsumi, W., & Oku, N. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21449 · Cited by 37 · see citing works
Self-citationRelease of synaptic zinc is substantially depressed by conventional brain slice preparations
Suh, S. W., Danscher, G., Jensen, M. S., et al. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02675-5 · Cited by 36 · see citing works
Suzuki, M., Fujise, Y., Tsuchiya, Y., Tamano, H., & Takeda, A. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.05.006 · Cited by 34 · see citing works
Self-citationIntracellular Zn2+signaling in cognition
Takeda, A., Fujii, H., Minamino, T., et al. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23385 · Cited by 34 · see citing works
Self-citationOntogeny of object-in-context recognition in the rat
Ramsaran, A. I., Westbrook, S. R., & Stanton, M. E. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.04.011 · Cited by 33 · see citing works
The hippocampus is sensitive to the mismatch in novelty between items and their contexts
Thakral, P. P., Yu, S. S., & Rugg, M. (2015) · Brain Research · doi:10.1016/j.brainres.2015.01.033 · Cited by 29 · see citing works
Tamano, H., Minamino, T., Fujii, H., Takada, S., Nakamura, M., Ando, M., & Takeda, A. (2015) · Hippocampus · doi:10.1002/hipo.22418 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Beneficial Effects of Spirulina Consumption on Brain Health
Trotta, T., Porro, C., Cianciulli, A., & Panaro, M. A. (2022) · Nutrients · doi:10.3390/nu14030676 · Cited by 98 · see citing works
Sinha, S., Patro, N., & Patro, I. K. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.181 · Cited by 39 · see citing works
- Authors
- Takeda, A., Suzuki, M., Tempaku, M., Ohashi, K., & Tamano, H.
- Affiliations
- Shizuoka University (JP)
- Corresponding author
- Takeda, A.
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 304
- Pages
- 209-216
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1027953470
- Cited by
- 29
- References
- 33
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 6 · 2015: 2
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25293032)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- extracellular zinc, hippocampal CA1, long-term potentiation, zinc influx, zinc chelators, object recognition memory, cognitive performance, pyramidal neurons, zinc chloride
- MeSH terms
- Animals, Cations, Chelating Agents, Chlorides, Cognition, Dose-Response Relationship, Drug, Extracellular Space, Male, Memory Disorders, Microelectrodes, Neurons, Neuropsychological Tests, Psychotropic Drugs, Zinc, Rats, Wistar, Microdialysis, Long-Term Potentiation, Zinc Compounds, Excitatory Postsynaptic Potentials, Recognition, Psychology, CA1 Region, Hippocampal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
