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Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression
Abstract
Maternal care in the rat influences the development of cognitive function in the offspring through neural systems known to mediate activity-dependent synaptic plasticity. The offspring of mothers that exhibit increased levels of pup licking/grooming (high-LG mothers) show increased hippocampal N-methyl-D-aspartate (NMDA) subunit mRNA expression, enhanced synaptogenesis and improved hippocampal-dependent spatial learning in comparison with animals reared by low-LG mothers. The effects of reduced maternal care on cognitive function are reversed with peripubertal environmental enrichment; however, the neural mechanisms mediating this effect are not known. In these studies we exposed the offspring of high- and low-LG mothers to environmental enrichment from days 22 to 70 of life, and measured the expression of genes encoding for glutamate receptor subunits and synaptophysin expression as a measure of synaptic density. Environmental enrichment reversed the effects of maternal care on synaptic density and this effect was, in turn, associated with a reversal of the effect of maternal care on the NR2A and NR2B subunits of the NMDA receptor, as well as effects on (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. Finally, direct infusion of an NR2B-specific NMDA receptor antagonist into the hippocampus eliminated the effects of maternal care on spatial learning/memory in the Morris water maze. These findings suggest that: (1) the effects of maternal care are mediated by changes in NR2B gene expression; and (2) that environmental enrichment reverses the effects of reduced maternal care through the same genomic target, the NR2B gene, and possibly effects on other subunits of the NMDA and AMPA receptors.
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“There is also evidence suggesting that the neural plasticity associated with adolescent development makes this a period of renewal and remediation (e.g., Bredy et al., 2004) capable of reprogramming the effects of earlier life in ways consistent with current experience.”
From Adolescent neurobiological susceptibility to social context (2016) · cites this paper as Bredy et al., 2004
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
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
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Sharma, S., Pearson, D., Plotsky, P. M., & Meaney, M. J. (1997) · Science · doi:10.1126/science.277.5332.1659 · Cited by 3,170
Self-citationMeaney, M. J. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1161 · Cited by 2,708
Self-citationHeteromeric NMDA receptors: molecular and functional distinction of subtypes
Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., & Seeburg, P. H. (1992) · Science · doi:10.1126/science.256.5060.1217 · Cited by 2,541
Neural 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 adaptive significance of maternal effects
Mousseau, T. A. (1998) · Trends in Ecology & Evolution · doi:10.1016/s0169-5347(98)01472-4 · Cited by 2,016
Nongenomic Transmission Across Generations of Maternal Behavior and Stress Responses in the Rat
Francis, D., Diorio, J., Liu, D., & Meaney, M. J. (1999) · Science · doi:10.1126/science.286.5442.1155 · Cited by 1,965
Self-citationGenetic 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
Maternal Effects As Adaptations
(1998) · doi:10.1093/oso/9780195111637.001.0001 · Cited by 1,653
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
Self-citationChampagne, F. A., Francis, D. D., Mar, A., & Meaney, M. J. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00149-5 · Cited by 1,021
Cole, A. J., Saffen, D. W., Baraban, J. M., & Worley, P. F. (1989) · Nature · doi:10.1038/340474a0 · Cited by 1,010
Guzowski, J. F., Lyford, G. L., Stevenson, G. D., Houston, F. P., McGaugh, J. L., Worley, P. F., & Barnes, C. A. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-03993.2000 · Cited by 992
Transgenerational induction of defences in animals and plants
Agrawal, A. A., Laforsch, C., & Tollrian, R. (1999) · Nature · doi:10.1038/43425 · Cited by 862
Steward, O., Wallace, C. S., Lyford, G., & Worley, P. (1998) · Neuron · doi:10.1016/s0896-6273(00)80591-7 · Cited by 845
Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval
Roozendaal, B. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2002.4080 · Cited by 838
Rampon, C., Tang, Y.-P., Goodhouse, J., Shimizu, E., Kyin, M., & Tsien, J. Z. (2000) · Nature Neuroscience · doi:10.1038/72945 · Cited by 755 · cited 13×
“Tukey–Kramer post-hoc analysis revealed that the effect was most pronounced in area CA1 where, under standard housing conditions, the offspring of low-LG mothers showed reduced expression of GluR3 mRNA compared with ª 2004 Federation of European Neuroscience Societies, European Journal of Neuroscience, 20, 1355–1362 t…”
BackgroundInfluentialEnvironmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective
Young, D., Lawlor, P. A., Leone, P., Dragunow, M., & During, M. J. (1999) · Nature Medicine · doi:10.1038/7449 · Cited by 745
Guzowski, J. F., Setlow, B., Wagner, E. K., & McGaugh, J. L. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05089.2001 · Cited by 718
Differential expression of immediate early genes in the hippocampus and spinal cord
Wisden, W., Errington, M. L., Williams, S., Dunnett, S. B., Waters, C. M., Hitchcock, D., Evan, G. I., Bliss, T., & Hunt, S. P. (1990) · Neuron · doi:10.1016/0896-6273(90)90118-y · Cited by 682
Moser, M., Trommald, M., & Andersen, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12673 · Cited by 617
Effects of environmental enrichment on gene expression in the brain
Rampon, C., Jiang, C. H., Dong, H., Tang, Y., Lockhart, D. J., Schultz, P. G., Tsien, J. Z., & Hu, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12880 · Cited by 614
Impaired spatial and sequential learning in rats treated neonatally with d ‐fenfluramine
Morford, L. L., Inman-Wood, S. L., Gudelsky, G. A., Williams, M. T., & Vorhees, C. V. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02100.x · Cited by 454
Smith, T. D., Adams, M. M., Gallagher, M., Morrison, J. H., & Rapp, P. R. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06587.2000 · Cited by 397
Falkenberg, T., Mohammed, A. K., Henriksson, B. G., Persson, H., Winblad, B. G., & Lindefors, N. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90494-r · Cited by 388
Duffy, S. N., Craddock, K. J., Abel, T. G., & Nguyen, P. (2001) · Learning & Memory · doi:10.1101/lm.36301 · Cited by 349
Differential effects of enrichment on learning and memory function in NR2B transgenic mice
Tang, Y., Wang, H., Feng, R., Kyin, M., & Tsien, J. Z. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00122-8 · Cited by 343
Cameron, N. M., Champagne, F. A., Parent, C., Fish, E. W., Ozaki-Kuroda, K., & Meaney, M. J. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.022 · Cited by 320
Self-citationCooper, R. M., & Zubek, J. P. (1958) · Canadian Journal of Psychology/Revue Canadienne de Psychologie · doi:10.1037/h0083747 · Cited by 280
Bredy, T. W., Humpartzoomian, R., Cain, D. P., & Meaney, M. J. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00918-1 · Cited by 253
Modification of hippocampal neurogenesis and neuroplasticity by social environments
Lü, L., Bao, G., Chen, H., Xia, P., Fan, X., Zhang, J., Pei, G., & Ma, L. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00248-6 · Cited by 245
Fernández‐Teruel, A., Escorihuela, R. M., Castellano, B., González, B., & Tobeña, A. (1997) · Behavior Genetics · doi:10.1023/a:1021400830503 · Cited by 212
Guilarte, T. R., Toscano, C. D., McGlothan, J. L., & Weaver, S. (2002) · Annals of Neurology · doi:10.1002/ana.10399 · Cited by 207
Regulation of synapsin I gene expression by the zinc finger transcription factor zif268/egr-1.
Thiel, G., Schoch, S., & Petersohn, D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36605-x · Cited by 204
Quantitative Synaptic Changes With Differential Experience In Rat Brain
Møllgaard, K., Diamond, M. C., Bennett, E. L., Rosenzweig, M. R., & Lindner, B. (1971) · International Journal of Neuroscience · doi:10.3109/00207457109148764 · Cited by 195
Early-life handling stimulation and environmental enrichment
Fernández-Teruel, A., Giménez-Llort, L., Escorihuela, R. M., Gil, L., Aguilar, R., Steimer, T., & Tobeña, A. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00787-6 · Cited by 171
Richardson, C. L., Tate, W. P., Mason, S. E., Lawlor, P. A., Dragunow, M., & Abraham, W. C. (1992) · Brain Research · doi:10.1016/0006-8993(92)90938-6 · Cited by 171
Pham, T. M., Söderström, S., Winblad, B., & Mohammed, A. H. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00019-4 · Cited by 162
A Molecular Mechanism for Stabilization of Learning-Induced Synaptic Modifications
Quinlan, E. M., Lebel, D., Brosh, I., & Barkai, E. (2004) · Neuron · doi:10.1016/s0896-6273(03)00874-2 · Cited by 161
Saito, S., Kobayashi, S., Ohashi, Y., Igarashi, M., Komiya, Y., & Ando, S. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390108 · Cited by 156
Koo, J. W., Park, C. H., Choi, S. H., Kim, N. J., Kim, H., Choe, J. C., & Suh, Y. (2003) · The FASEB Journal · doi:10.1096/fj.02-1032fje · Cited by 155
An emerging molecular and cellular framework for memory processing by the hippocampus
Wittenberg, G. M. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02231-2 · Cited by 148
Moga, D. E., Calhoun, M. E., Chowdhury, A., Worley, P., Morrison, J. H., & Shapiro, M. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.02.004 · Cited by 134
Ghasemzadeh, M. B., Nelson, L. C., Lu, X., & Kalivas, P. W. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720157.x · Cited by 133
Mechanism of altered synaptic strength due to experience: relation to long-term potentiation
Foster, T. C., Gagné, J., & Massicotte, G. (1996) · Brain Research · doi:10.1016/0006-8993(96)00707-x · Cited by 131
Experience-Dependent Regulation of the Immediate-Early Gene Arc Differs across Brain Regions
Kelly, M. P., & Deadwyler, S. A. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-16-06443.2003 · Cited by 130
Acquisition of a novel behavior induces higher levels of Arc mRNA than does overtrained performance
Kelly, M. P., & Deadwyler, S. A. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00605-4 · Cited by 116
Tsai, K., Chen, S., Ma, Y., Hsu, W., & Lee, E. H. Y. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062405399 · Cited by 105
Myers, M. M., Brunelli, S. A., Shair, H. N., Squire, J. M., & Hofer, M. A. (1989) · Developmental Psychobiology · doi:10.1002/dev.420220105 · Cited by 96
Lee, E. H. Y., Hsu, W., Ma, Y., Lee, P. J., & Chao, C.-C. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.03032.x · Cited by 91
Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat
Verstynen, T., Tierney, R. P., Urbanski, T., & Tang, A. C. (2001) · Neuroreport · doi:10.1097/00001756-200110080-00008 · Cited by 63
Neonatal exposure to novelty enhances long‐term potentiation in CA1 of the rat hippocampus
Tang, A. C., & Zou, B. (2002) · Hippocampus · doi:10.1002/hipo.10017 · Cited by 56
Richter‐Landsberg, C., & Gorath, M. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990501)56:3 · Cited by 52
Synaptic plasticity in rat hippocampus associated with learning
Reempts, J. V., Dikova, M., Werbrouck, L., Clincke, G., & Borgers, M. J. (1992) · Behavioural Brain Research · doi:10.1016/s0166-4328(05)80211-6 · Cited by 39
Grimwood, S., Richards, P., Murray, F., Harrison, N., Wingrove, P. B., & Hutson, P. H. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0752455.x · Cited by 39
Infantile Handling Eliminates Reversal Learning Deficit in Rats Prenatally Exposed to Alcohol
Lee, M. H., & Rabe, A. (1999) · Alcohol · doi:10.1016/s0741-8329(98)00067-6 · Cited by 39
Decreased NGFI-A gene expression in the hippocampus of cognitively impaired aged rats
Yau, J. L. W., Olsson, T., Morris, R., Noble, J., & Seckl, J. R. (1996) · Molecular Brain Research · doi:10.1016/s0169-328x(96)00220-3 · Cited by 33
Nilsson (1999) · doi:10.1002/(sici)1097-4695(19990615)39:4
Research works printed but not linked: 2
- Hinde R.A., 1986, Development of Anti‐Social and Prosocial Behaviour, 13
- O'Leary S.K., 2002, Persistence of environmental enrichment effects after prenatal alcohol exposure on Morris water maze performance, Dev. Psychobiol., 41, 318
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Huppert, F. A. (2009) · Applied Psychology: Health and Well-Being · doi:10.1111/j.1758-0854.2009.01008.x · Cited by 1,583
Socioeconomic status and the brain: mechanistic insights from human and animal research
Hackman, D. A., Farah, M. J., & Meaney, M. J. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2897 · Cited by 1,409
Self-citationEpigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239
Self-citationStress effects on memory: An update and integration
Schwabe, L., Joëls, M., Roozendaal, B., Wolf, O. T., & Oitzl, M. S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.07.002 · Cited by 714
Kaufman, J., Yang, B.-Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., Krystal, J. H., & Gelernter, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.026 · Cited by 692
Metadata
- Authors
- Bredy, T. W., Zhang, T. Y., Grant, R. J., Diorio, J., & Meaney, M. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- McGill University (CA)
- Corresponding author
- Meaney, Michael J.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-09
- Volume
- 20
- Issue
- 5
- Pages
- 1355-1362
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2136757585
- Cited by
- 196
- References
- 59
- Citations by year
- 2026: 5 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 11 · 2017: 3 · 2016: 9 · 2015: 21 · 2014: 7 · 2013: 11 · 2012: 15
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- maternal care, environmental enrichment, hippocampus, NMDA receptor, NR2B subunit, AMPA receptors, glutamate receptor subunits, synaptophysin, synaptic density, spatial learning and memory, peripubertal period, synaptic plasticity, gene expression
- MeSH terms
- Age Factors, Animals, Environment, Female, Hippocampus, Male, Maternal Behavior, Receptors, Glutamate, Gene Expression Regulation, Developmental, Maze Learning, Rats, Long-Evans, Protein Subunits, Rats
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