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Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice
Abstract
We produced CA1-specific NMDA receptor 1 subunit-knockout (CA1-KO) mice to determine the NMDA receptor dependence of nonspatial memory formation and of experience-induced structural plasticity in the CA1 region. CA1-KO mice were profoundly impaired in object recognition, olfactory discrimination and contextual fear memories. Surprisingly, these deficits could be rescued by enriching experience. Using stereological electron microscopy, we found that enrichment induced an increase of the synapse density in the CA1 region in knockouts as well as control littermates. Therefore, our data indicate that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes.
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“mice with selective NMDA-R subunit 1 knockout in the hippocampal CA1 area exhibited NOP deficits”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Rampon et al., 2000
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS
Scoville, W. B., & Milner, B. (1957) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.20.1.11 · Cited by 7,322
Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans.
Squire, L. R. (1992) · Psychological Review · doi:10.1037/0033-295x.99.2.195 · Cited by 5,376
More hippocampal neurons in adult mice living in an enriched environment
Kempermann, G., Kuhn, H. G., & Gage, F. H. (1997) · Nature · doi:10.1038/386493a0 · Cited by 3,586
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258
The unbiased estimation of number and sizes of arbitrary particles using the disector
Sterio, D. C. (1984) · Journal of Microscopy · doi:10.1111/j.1365-2818.1984.tb02501.x · Cited by 2,533
Zola-Morgan, S., Squire, L., & Amaral, D. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-10-02950.1986 · Cited by 1,997
Genetic enhancement of learning and memory in mice
Tang, Y., Shimizu, E., Dubé, G., Rampon, C., Kerchner, G. A., Zhuo, M., Liu, G., & Tsien, J. Z. (1999) · Nature · doi:10.1038/43432 · Cited by 1,878
Self-citationThe 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
Self-citationMolecular cloning and characterization of the rat NMDA receptor
Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N., & Nakanishi, S. (1991) · Nature · doi:10.1038/354031a0 · Cited by 1,771
Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study.
Eg, G. (1959) · PubMed · Cited by 1,768
Developmental mechanisms that generate precise patterns of neuronal connectivity
Goodman, C. S., & Shatz, C. J. (1993) · Cell · doi:10.1016/s0092-8674(05)80030-3 · Cited by 1,425
Synaptic plasticity: LTP and LTD
Bear, M. F., & Malenka, R. C. (1994) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(94)90101-5 · Cited by 1,355
Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain
Tsien, J. Z., Chen, D. F., Gerber, D., Tom, C., Mercer, E. H., Anderson, D. J., Mayford, M., Kandel, E. R., & Tonegawa, S. (1996) · Cell · doi:10.1016/s0092-8674(00)81826-7 · Cited by 1,280
Self-citationNotes on the estimation of the numerical density of arbitrary profiles: the edge effect
Gundersen, H. J. G. (1977) · Journal of Microscopy · doi:10.1111/j.1365-2818.1977.tb00062.x · Cited by 1,265
Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons
Woolley, C., Gould, E., Frankfurt, M., & McEwen, B. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-12-04035.1990 · Cited by 1,107
Contrasting properties of two forms of long-term potentiation in the hippocampus
Nicoll, R. A., & Malenka, R. C. (1995) · Nature · doi:10.1038/377115a0 · Cited by 861
Structural Changes Accompanying Memory Storage
Bailey, C. H., & Kandel, E. R. (1993) · Annual Review of Physiology · doi:10.1146/annurev.ph.55.030193.002145 · Cited by 856
Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat
Burwell, R. D., & Amaral, D. G. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980824)398:2 · Cited by 734
The global record of memory in hippocampal neuronal activity
Wood, E. R., Dudchenko, P. A., & Eichenbaum, H. (1999) · Nature · doi:10.1038/17605 · Cited by 707
Moser, M., Trommald, M., & Andersen, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12673 · Cited by 617
Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice
McHugh, T. J., Blum, K. I., Tsien, J. Z., Tonegawa, S., & Wilson, M. A. (1996) · Cell · doi:10.1016/s0092-8674(00)81828-0 · Cited by 593
Self-citationLi, Y., Erzurumlu, R. S., Chen, C., Jhaveri, S., & Tonegawa, S. (1994) · Cell · doi:10.1016/0092-8674(94)90108-2 · Cited by 466
Rosene, D. L., & Van Hoesen, G. W. (1987) · Cerebral Cortex · doi:10.1007/978-1-4615-6616-8_9 · Cited by 422
Expression Mechanisms Underlying NMDA Receptor‐Dependent Long‐Term Potentiation
Nicoll, R. A., & Malenka, R. C. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11320.x · Cited by 378
Mansuy, I. M., Mayford, M. R., Jacob, B., Kandel, E. R., & Bach, M. E. (1998) · Cell · doi:10.1016/s0092-8674(00)80897-1 · Cited by 362
Spaced training induces normal long-term memory in CREB mutant mice
Kogan, J. H., Frankland, P. W., Blendy, J. A., Coblentz, J., Marowitz, Z., Schütz, G., & Silva, A. J. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00022-4 · Cited by 350
Environmental complexity, cerebral change, and behavior.
Rosenzweig, M. R. (1966) · American Psychologist · doi:10.1037/h0023555 · Cited by 277
Bunsey, M. D., & Eichenbaum, H. (1995) · Hippocampus · doi:10.1002/hipo.450050606 · Cited by 268
Enriching heredity: the impact of the environment on the anatomy of the brain
(1989) · Choice Reviews Online · doi:10.5860/choice.26-3265 · Cited by 220
Dendrites are more spiny on mature hippocampal neurons when synapses are inactivated
Kirov, S. A., & Harris, K. M. (1999) · Nature Neuroscience · doi:10.1038/13178 · Cited by 194
Stability in Synapse Number and Size at 2 Hr after Long-Term Potentiation in Hippocampal Area CA1
Sorra, K. E., & Harris, K. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-02-00658.1998 · Cited by 181
Fiala, B. A., Joyce, J. N., & Greenough, W. T. (1978) · Experimental Neurology · doi:10.1016/0014-4886(78)90229-7 · Cited by 129
The ‘single’ section Golgi-impregnation procedure: methodological description
Gabbott, P. L. A., & Somogyi, J. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90084-0 · Cited by 127
Social transmission of food preferences in adult hooded rats (Rattus norvegicus).
Strupp, B. J., & Levitsky, D. A. (1984) · Journal of comparative psychology · doi:10.1037/0735-7036.98.3.257 · Cited by 106
A structural basis for memory storage in mammals
Woolf, N. J. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00094-4 · Cited by 103
Mumby, D. G., Wood, E. R., Duva, C. A., Kornecook, T. J., Pinel, J. P. J., & Phillips, A. G. (1996) · Behavioral Neuroscience · doi:10.1037//0735-7044.110.2.266 · Cited by 93
A critical evaluation of methods for estimating the numerical density of synapses
de Groot, D. M. G., & Bierman, E. P. B. (1986) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(86)90113-5 · Cited by 83
Stevens, C. F., & Sullivan, J. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70097-1 · Cited by 32
Preoperative differential housing and dorsal hippocampal lesions in rats.
Dalrymple‐Alford, J. C., & Benton, D. (1984) · Behavioral Neuroscience · doi:10.1037//0735-7044.98.1.23 · Cited by 14
Preoperative differential housing and dorsal hippocampal lesions in rats.
Dalrymple‐Alford, J. C., & Benton, D. (1984) · Behavioral Neuroscience · doi:10.1037/0735-7044.98.1.23 · Cited by 13
Flagged first, then by citations
Research works printed but not linked: 2
- Greenough, W. T., Withers, G. S. & Wallace, C. S. in The Biology of Memory (eds. Squire, L. R. & Lindenbaum, E.) 159–185 (Schattauer, Stuttgart, 1990).
- Gray, E. G. Axosomatic and axodendritic synapses of the cerebral cortex: An electron microscopic study. J. Anat. 83, 420– 433 (1959).
Cited by
Sorted by citations
Squire, L. R., Stark, C. E. L., & Clark, R. E. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144130 · Cited by 2,680
“Similar findings were obtained after intrahippocampal injections of APV (Baker & Kim 2002) and in mice lacking the NMDAR-1 subunit in the hippocampal region (Rampon et al. 2000).”
ResultNeural consequences of enviromental enrichment
van Praag, H., Kempermann, G., & Gage, F. H. (2000) · Nature Reviews Neuroscience · doi:10.1038/35044558 · Cited by 2,468
The novel object recognition memory: neurobiology, test procedure, and its modifications
Antunes, M., & Biala, G. (2012) · Cognitive Processing · doi:10.1007/s10339-011-0430-z · Cited by 2,390
Neurobiology of Pavlovian fear conditioning
Maren, S. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.897 · Cited by 1,543
“Contextual fear conditioning deficits in hippocampal NMDA receptor–knockout mice are overcome by P1: FQP April 4, 2001 18:39 Annual Reviews AR121-29 918 MAREN environmental enrichment (Rampon et al 2000).”
BackgroundEnriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771
Metadata
- Authors
- Rampon, C., Tang, Y.-P., Goodhouse, J., Shimizu, E., Kyin, M., & Tsien, J. Z.
- Affiliations
- Princeton University (US)
- Corresponding author
- Tsien, Joe Z.
- Venue
- Nature Neuroscience
- Published
- 2000-03-01
- Volume
- 3
- Issue
- 3
- Pages
- 238-244
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1481984979
- Semantic Scholar
- fa40536e2cbc3bd383f248197b5f4cb17804cd65
- Cited by
- 755
- References
- 41
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 20 · 2022: 12 · 2021: 16 · 2020: 20 · 2019: 20 · 2018: 22 · 2017: 22 · 2016: 32 · 2015: 30 · 2014: 33 · 2013: 40 · 2012: 44
- FWCI
- 15.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health
- Arnold and Mabel Beckman Foundation
- Princeton University
- 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 1, CA1, hippocampus, memory impairment, object recognition memory, odor discrimination, contextual fear memory, environmental enrichment, synaptic plasticity, synaptic density, knockout mice, memory recovery
- MeSH terms
- Animals, Conditioning, Psychological, Cues, Dendrites, Electroshock, Exploratory Behavior, Fear, Female, Food Preferences, Male, Memory, Memory Disorders, Pattern Recognition, Visual, Smell, Space Perception, Synapses, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Pyramidal Cells, Mice, Knockout, Mice
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