Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice
Open accessAbstract
To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of pairs of neurons tuned to similar spatial locations. Pairs have uncorrelated firing even if their fields overlap. These results demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the proper representation of space in the CA1 region of the hippocampus.
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?
Genetic deletion of GluN1 in the CA1 region of the hippocampus decreases the spatial specificity of place fields.
“and the genetic deletion of GluN1 in the CA1 region of the hippocampus decreases the spatial specificity of place fields (420).”
From Synaptic memory and CaMKII (2023) · cites this paper as [420]
Cites
Bienenstock, E., Cooper, L., & Munro, P. (1982) · The Journal of Neuroscience · doi:10.1523/jneurosci.02-01-00032.1982 · Cited by 2,896 · see citing works
Dynamics of the Hippocampal Ensemble Code for Space
Wilson, M. A., & McNaughton, B. L. (1993) · Science · doi:10.1126/science.8351520 · Cited by 2,350 · see citing works
Self-citationZola-Morgan, S., Squire, L., & Amaral, D. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-10-02950.1986 · Cited by 1,997 · see citing works
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917 · see citing works
Meaney, M. J. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1161 · Cited by 2,708 · see citing works
Place Cells, Grid Cells, and the Brain's Spatial Representation System
Moser, E. I., Kropff, E., & Moser, M.-B. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.061307.090723 · Cited by 1,934 · see citing works
The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
Tsien, J. Z., Huerta, P. T., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81827-9 · Cited by 1,782 · see citing works
Self-citationLong-term dynamics of CA1 hippocampal place codes
Ziv, Y., Burns, L. D., Cocker, E. D., Hamel, E. O., Ghosh, K. K., Kitch, L. J., Gamal, A. E., & Schnitzer, M. J. (2013) · Nature Neuroscience · doi:10.1038/nn.3329 · Cited by 1,155 · see citing works
Maternal care, hippocampal synaptogenesis and cognitive development in rats
Liu, D., Diorio, J., Day, J. C., Francis, D. D., & Meaney, M. J. (2000) · Nature Neuroscience · doi:10.1038/77702 · Cited by 1,195 · see citing works
The Hippocampus, Memory, and Place Cells
Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M., & Tanila, H. (1999) · Neuron · doi:10.1016/s0896-6273(00)80773-4 · Cited by 1,064 · see citing works
Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network
McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., Fanselow, M. S., Wilson, M. A., & Tonegawa, S. (2007) · Science · doi:10.1126/science.1140263 · Cited by 958 · see citing works
Self-citationZhang, K., Ginzburg, I., McNaughton, B. L., & Sejnowski, T. J. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.2.1017 · Cited by 741 · see citing works
Rampon, C., Tang, Y.-P., Goodhouse, J., Shimizu, E., Kyin, M., & Tsien, J. Z. (2000) · Nature Neuroscience · doi:10.1038/72945 · Cited by 737 · see citing works
Self-citationNMDA receptors, place cells and hippocampal spatial memory
Nakazawa, K., McHugh, T. J., Wilson, M. A., & Tonegawa, S. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1385 · Cited by 619 · see citing works
Self-citationDirect recordings of grid-like neuronal activity in human spatial navigation
Jacobs, J., Weidemann, C. T., Miller, J. F., Solway, A., Burke, J. F., Wei, X.-X., Suthana, N., Sperling, M. R., Sharan, A. D., Fried, I., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3466 · Cited by 564 · see citing works
Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons
Bittner, K. C., Grienberger, C., Vaidya, S. P., Milstein, A. D., Macklin, J. J., Suh, J., Tonegawa, S., & Magee, J. C. (2015) · Nature Neuroscience · doi:10.1038/nn.4062 · Cited by 540 · see citing works
Self-citationSIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity
Michan, S., Li, Y., Chou, M. M.-H., Parrella, E., Ge, H., Long, J. M., Allard, J. S., Lewis, K., Miller, M., Xu, W., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0027-10.2010 · Cited by 541 · see citing works
Hippocampal network patterns of activity in the mouse
Buzsáki, G., Buhl, D. L., Harris, K. D., Csicsvari, J., Czéh, B., & Morozov, A. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00669-3 · Cited by 486 · see citing works
Korotkova, T., Fuchs, E. C., Ponomarenko, A., von Engelhardt, J., & Monyer, H. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.017 · Cited by 480 · see citing works
Abolition of Long-Term Stability of New Hippocampal Place Cell Maps by NMDA Receptor Blockade
Kentros, C., Hargreaves, E., Hawkins, R. D., Kandel, E. R., Shapiro, M., & Muller, R. V. (1998) · Science · doi:10.1126/science.280.5372.2121 · Cited by 484 · see citing works
Foster, D. J. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031538 · Cited by 375 · see citing works
Epigenetic programming of stress responses through variations in maternal care
FISH, E. W., SHAHROKH, D., BAGOT, R., CALDJI, C., BREDY, T., SZYF, M., & MEANEY, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1330.011 · Cited by 361 · see citing works
Grid cells and cortical representation
Moser, E. I., Roudi, Y., Witter, M. P., Kentros, C., Bonhoeffer, T., & Moser, M.-B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3766 · Cited by 335 · see citing works
NMDA receptors and memory encoding
Morris, R. G. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.014 · Cited by 295 · see citing works
Nicotinic Stimulation Produces Multiple Forms of Increased Glutamatergic Synaptic Transmission
Radcliffe, K. A., & Dani, J. A. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-18-07075.1998 · Cited by 271 · see citing works
Neighborhood matters: divergent patterns of stress-induced plasticity across the brain
Chattarji, S., Tomar, A., Suvrathan, A., Ghosh, S., & Rahman, M. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4115 · Cited by 248 · see citing works
Impaired path integration in mice with disrupted grid cell firing
Gil, M., Ancau, M., Schlesiger, M. I., Neitz, A., Allen, K., De Marco, R. J., & Monyer, H. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0039-3 · Cited by 174 · see citing works
Baraban, S. C., & Tallent, M. K. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.01.008 · Cited by 187 · see citing works
Cho, Y. H., Giese, K. P., Tanila, H., Silva, A. J., & Eichenbaum, H. (1998) · Science · doi:10.1126/science.279.5352.867 · Cited by 189 · see citing works
McDermott, C. M., Hardy, M. N., Bazan, N. G., & Magee, J. C. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2005.093781 · Cited by 178 · see citing works
Ding, Q., Vaynman, S., Souda, P., Whitelegge, J. P., & Gomez‐Pinilla, F. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05026.x · Cited by 174 · see citing works
Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia†
Greene, R. (2001) · Hippocampus · doi:10.1002/hipo.1072 · Cited by 140 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
Lenck-Santini, P.-P., Rivard, B., Muller, R. U., & Poucet, B. (2005) · Hippocampus · doi:10.1002/hipo.20060 · Cited by 81 · see citing works
Vyssotski, A. L., Dell'Omo, G., Poletaeva, I. I., Vyssotski, D. L., Minichiello, L., Klein, R., Wolfer, D. P., & Lipp, H. (2002) · Hippocampus · doi:10.1002/hipo.10002 · Cited by 72 · see citing works
Linking hippocampal multiplexed tuning, Hebbian plasticity and navigation
Moore, J. J., Cushman, J. D., Acharya, L., Popeney, B., & Mehta, M. R. (2021) · Nature · doi:10.1038/s41586-021-03989-z · Cited by 69 · see citing works
Haettig, J., Sun, Y., Wood, M. A., & Xu, X. (2013) · Learning & Memory · doi:10.1101/lm.027847.112 · Cited by 41 · see citing works
Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine
Souza, M. A., Magni, D. V., Guerra, G. P., Oliveira, M. S., Furian, A. F., Pereira, L., Marquez, S. V., Ferreira, J., Fighera, M. R., & Royes, L. F. F. (2012) · Amino Acids · doi:10.1007/s00726-012-1329-4 · Cited by 42 · see citing works
Cognitive impairment in mice over-expressing γ-aminobutyric acid transporter I (GAT1)
Hu, J.-H., Ma, Y.-H., Jiang, J., Yang, N., Duan, S.-H., Jiang, Z.-H., Mei, Z.-T., Fei, J., & Guo, L.-H. (2004) · NeuroReport · doi:10.1097/00001756-200401190-00003 · Cited by 26 · see citing works
Differential Impact of Acute and Chronic Stress on CA1 Spatial Coding and Gamma Oscillations
Tomar, A., Polygalov, D., & McHugh, T. J. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.710725 · Cited by 21 · see citing works
Self-citationPast, present, and future of psychiatry: personal reflections
Eisenberg, L. (1997) · The Canadian Journal of Psychiatry · doi:10.1177/070674379704200702 · Cited by 10 · see citing works
- Authors
- McHugh, T. J., Blum, K. I., Tsien, J. Z., Tonegawa, S., & Wilson, M. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Tonegawa, Susumu
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 87
- Issue
- 7
- Pages
- 1339-1349
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1988633143
- Cited by
- 593
- References
- 4
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 25 · 2020: 11 · 2019: 16 · 2018: 23 · 2017: 20 · 2016: 19 · 2015: 23 · 2014: 23 · 2013: 19 · 2012: 24
- FWCI
- 17.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-32925, R01NS032925)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- NMDA receptor, CA1 pyramidal neurons, place cells, place fields, spatial representation, synaptic plasticity, freely moving mice
- MeSH terms
- Action Potentials, Animals, Behavior, Animal, Electrophysiology, Hippocampus, Memory, Neuronal Plasticity, Space Perception, Synapses, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Maze Learning, Mice
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