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Learning deficit in BDNF mutant mice.
Abstract
Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of high-frequency synaptic transmission and long-term potentiation in the hippocampus, processes that are also thought to be involved in the learning of spatial tasks such as the Morris water maze. In order to determine whether BDNF is required for normal spatial learning, mice carrying a deletion in one copy of the BDNF gene were subjected to the Morris water maze task. Young adult BDNF mutant mice were significantly impaired compared with wild-type mice, requiring twice the number of days to reach full performance. Aged wild-type mice performed significantly worse than young wild-type mice and the effect was even more pronounced in the BDNF mutant mice, which did not learn at all. Although there was no difference in mean swimming speed between BDNF mutant and wild-type mice, we cannot exclude the possibility that developmental or peripheral deficits also contribute to the learning deficits in these mice. In situ hybridization and RNase protection analysis revealed that BDNF mRNA expression was indeed decreased in BDNF mutant mice. Furthermore, a pronounced effect of age on BDNF mRNA expression was seen, displayed as both a reduced level of mRNA expression and a reduced or entirely absent layer-specific expression pattern in the cerebral cortex of aged animals. Thus, our data suggest that BDNF expression may be linked to learning.
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“The importance of BDNF to hippocampal neuroplasticity is epitomized by animal studies, which have found that the manipulation of BDNF expression directly impacts upon performance in spatial and contextual memory tasks (Linnarsson et al., 1997; Alonso et al., 2002; Heldt et al., 2007; Peters et al., 2010), and also that the downregulation of BDNF inhibits AE induced improvements in spatial memory”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Linnarsson et al., 1997
Citations
Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
Physiology of the Neurotrophins
Lewin, G. R., & Barde, Y. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.19.030196.001445 · Cited by 1,959
Neurotrophins and Neuronal Plasticity
Thoenen, H. (1995) · Science · doi:10.1126/science.270.5236.593 · Cited by 1,927
Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H., & Bonhoeffer, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8856 · Cited by 1,426
Long-Lasting Neurotrophin-Induced Enhancement of Synaptic Transmission in the Adult Hippocampus
Kang, H., & Schuman, E. M. (1995) · Science · doi:10.1126/science.7886457 · Cited by 1,354
Patterson, S. L., Abel, T., Deuel, T. A. S., Martin, K. C., Rose, J. C., & Kandel, E. R. (1996) · Neuron · doi:10.1016/s0896-6273(00)80140-3 · Cited by 1,233
Figurov, A., Pozzo-Miller, L. D., Olafsson, P., Wang, T., & Lu, B. (1996) · Nature · doi:10.1038/381706a0 · Cited by 1,106
Mice lacking brain-derived neurotrophic factor develop with sensory deficits
Ernfors, P., Lee, K.-F., & Jaenisch, R. (1994) · Nature · doi:10.1038/368147a0 · Cited by 1,067
Self-citationRegional distribution of brain‐derived neurotrophic factor mRNA in the adult mouse brain.
Hofer, M., Pagliusi, S. R., Hohn, A., Leibrock, J., & Barde, Y. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07423.x · Cited by 1,039
A Requirement for Local Protein Synthesis in Neurotrophin-Induced Hippocampal Synaptic Plasticity
Kang, H., & Schuman, E. M. (1996) · Science · doi:10.1126/science.273.5280.1402 · Cited by 996
Neurotrophins regulate dendritic growth in developing visual cortex
McAllister, A. K., Lo, D. C., & Katz, L. C. (1995) · Neuron · doi:10.1016/0896-6273(95)90171-x · Cited by 959
BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease
Phillips, H. S., Hains, J. M., Armanini, M., Laramee, G. R., Johnson, S. A., & Winslow, J. W. (1991) · Neuron · doi:10.1016/0896-6273(91)90273-3 · Cited by 921
Zafra, F., Hengerer, B., Leibrock, J., Thoenen, H., & Lindholm, D. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07564.x · Cited by 897
Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype?
Gerlai, R. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)20020-7 · Cited by 881
Multiple promoters direct tissue-specific expression of the rat BDNF gene
Timmusk, T., Palm, K., Metsis, M., Reintam, T., Paalme, V., Saarma, M., & Persson, H. (1993) · Neuron · doi:10.1016/0896-6273(93)90335-o · Cited by 858
Ernfors, P., Wetmore, C., Olson, L., & Persson, H. (1990) · Neuron · doi:10.1016/0896-6273(90)90090-3 · Cited by 819
Self-citationPotentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF
Lohof, A. M., Ip, N. Y., & Poo, M.-M. (1993) · Nature · doi:10.1038/363350a0 · Cited by 755
Isackson, P. J., Huntsman, M. M., Murray, K. D., & Gall, C. M. (1991) · Neuron · doi:10.1016/0896-6273(91)90234-q · Cited by 711 · cited 1×
“, 1990) or lesion-induced limbic seizures (Isackson et al., 1991), BDNF ml7NA is up-regulated in the cortex and hippocampus.”
BackgroundLevine, E. S., Dreyfus, C. F., Black, I. B., & Plummer, M. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.8074 · Cited by 611
Zafra, F., Ċastrén, E., Thoenen, H., & Lindholm, D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.22.10037 · Cited by 580
Inhibition of Ocular Dominance Column Formation by Infusion of NT-4/5 or BDNF
Cabelli, R. J., Hohn, A., & Shatz, C. J. (1995) · Science · doi:10.1126/science.7886458 · Cited by 566
Synaptic development of the cerebral cortex: implications for learning, memory and mental illness
(1994) · Progress in Brain Research · doi:10.1016/s0079-6123(08)60543-9 · Cited by 565
Patterson, S. L., Grover, L. M., Schwartzkroin, P. A., & Bothwell, M. (1992) · Neuron · doi:10.1016/0896-6273(92)90067-n · Cited by 555
Widespread Expression of BDNF But Not NT3 by Target Areas of Basal Forebrain Cholinergic Neurons
PHILLIPS, H. S., Hains, J. M., Laramee, G. R., Rosenthal, A., & Winslow, J. W. (1990) · Science · doi:10.1126/science.1688328 · Cited by 539
Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex.
Castrén, E., Zafra, F., Thoenen, H., & Lindholm, D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.20.9444 · Cited by 513
Spatial learning and motor deficits in aged rats
Gage, F. H., Dunnett, S. B., & Björklund, A. (1984) · Neurobiology of Aging · doi:10.1016/0197-4580(84)90084-8 · Cited by 507
BDNF, and NT-4/5 enhance glutamatergic synaptic transmission in cultured hippocampal neurones
Lemann, V., Gottmann, K., & Heumann, R. (1994) · NeuroReport · doi:10.1097/00001756-199412300-00007 · Cited by 402
Wetmore, C., Ernfors, P., Persson, H., & Olson, L. (1990) · Experimental Neurology · doi:10.1016/0014-4886(90)90068-4 · Cited by 370
Korte, M., Griesbeck, O., Gravel, C., Carroll, P., Staiger, V, Thoenen, H., & Bonhoeffer, T. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12547 · Cited by 351
Otto, T., Eichenbaum, H., Wible, C. G., & Wiener, S. I. (1991) · Hippocampus · doi:10.1002/hipo.450010206 · Cited by 311
The induction of LTP increases BDNF and NGF mRNA but decreases NT-3 mRNA in the dentate gyrus
Castrén, E., Pitkänen, M., Sirviö, J., Parsadanian, A., Lindholm, D., Thoenen, H., & Riekkinen, P. J. (1993) · NeuroReport · doi:10.1097/00001756-199307000-00014 · Cited by 308
Neurotrophins and activity-dependent development of the neocortex
Bonhoeffer, T. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80017-1 · Cited by 297
Biffo, S., Offenhäuser, N., Carter, B. D., & Barde, Y. (1995) · Development · doi:10.1242/dev.121.8.2461 · Cited by 270
Correlation between the Pharmacology of Long-Term Potentiation and the Pharmacology of Memory
Izquierdo, I., & Medina, J. H. (1995) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1995.1002 · Cited by 230
Edwards, F. A. (1995) · Physiological Reviews · doi:10.1152/physrev.1995.75.4.759 · Cited by 180
Synaptic plasticity: hippocampal LTP
Larkman, A. U., & Jack, J. (1995) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(95)80045-x · Cited by 173
Fischer, W., Sirevaag, A. M., Wiegand, S. J., Lindsay, R. M., & Björklund, A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8607 · Cited by 170
Synaptic structure and function: Dynamic organization yields architectural precision
Burns, M. E., & Augustine, G. J. (1995) · Cell · doi:10.1016/0092-8674(95)90160-4 · Cited by 170
Brain-derived neurotrophic factor expression after long-term potentiation
Dragunow, M., Beilharz, E. J., Mason, B., Lawlor, P. A., Abraham, W. C., & Gluckman, P. D. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90420-p · Cited by 156
Involvement of LTP in memory: Are we “searching under the street light”?
Barnes, C. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90166-3 · Cited by 155
Schoups, A. A., Elliott, R. C., Friedman, W., & Black, I. B. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(95)00043-d · Cited by 145
Ċastrén, E., Berzaghi, M. D. P., Lindholm, D., & Thoenen, H. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1124 · Cited by 101
Histology of the Nervous System
Guillery, R. W. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80029-4 · Cited by 76
Research works printed but not linked: 4
- Blöchl A., 1995, Life and Death in the Newous System, 260
- Galuske R. A. W., 1994, Chronic infusion of brain‐derived neurotrophic factor induces paradoxical ocular dominance shifts in the kitten visual cortex, Soc. Neurosci. Abstc, 20, 312
- Cmesbeck O., 1995, Characterization of brain‐derived neurotrophic factor (BDNF) secretion from hippocampal neumns, Soc. Neurosci. Abstx, 21, 417.12
- Purves D., 1988, A Trophic Theory of Neuronal Organization
Cited by
Sorted by citations
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,015
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888
Long-Term Potentiation and Memory
Lynch, M. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00014.2003 · Cited by 2,074
Binder (2004) · doi:10.1080/08977190410001723308 · Cited by 1,481
Brain foods: The effects of nutrients on brain function.
Gómez-Pinilla, F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2421 · Cited by 1,372
Metadata
- Authors
- Linnarsson, S., Björklund, A., & Ernfors, P.
- Affiliations
- Karolinska Institutet (SE)
- Lund University (SE)
- Corresponding author
- Linnarsson, Sten
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 1997-12
- Volume
- 9
- Issue
- 12
- Pages
- 2581-2587
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2136761139
- Cited by
- 471
- References
- 44
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 9 · 2017: 16 · 2016: 20 · 2015: 25 · 2014: 25 · 2013: 29 · 2012: 30
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancerfonden
- Vetenskapsrådet
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, BDNF knockout mice, spatial learning, Morris water maze, hippocampus, long-term potentiation, synaptic transmission, BDNF mRNA expression, age-related decline, cerebral cortex, learning deficits
- MeSH terms
- Age Factors, Animals, Mice, Inbred BALB C, Mice, Neurologic Mutants, Retention, Psychology, RNA, Messenger, Spatial Behavior, Long-Term Potentiation, Gene Expression Regulation, Developmental, Maze Learning, Brain-Derived Neurotrophic Factor, Mice
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