Neurotrophins and Time: Different Roles for TrkB Signaling in Hippocampal Long-Term Potentiation
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We examined the role of TrkB ligands in hippocampal long-term potentiation (LTP) using function-blocking TrkB antiserum (Ab) and Trk-IgG fusion proteins. Incubation of hippocampal slices with TrkB Ab had no effect on basal synaptic transmission, short-term plasticity, or LTP induced by several trains of tetanic stimulation. The TrkB Ab-treated slices, however, showed significant deficits in LTP induced by either theta-burst stimulation (TBS) or "pairing." Slices exposed to the same number of inducing stimuli, delivered either as TBS or as a single 100 Hz epoch, only exhibited TrkB-sensitive LTP when TBS was used, indicating that the temporal pattern of stimulation determines the neurotrophin dependence. The late phase of LTP (2-3 hr) was also significantly impaired in slices pretreated with TrkB Ab or a TrkB-IgG. The application of a TrkB-IgG 30 min after LTP induction caused previously potentiated synaptic transmission to return to baseline levels, indicating that TrkB ligands are required to maintain LTP for up to 1 hr after induction. Taken together, these results indicate that both the temporal patterns of synaptic activity and the different temporal phases of synaptic enhancement are important in determining the neurotrophin dependence of plasticity in the hippocampus.
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The nature of this BDNF requirement varies depending on the induction protocol.
“A late phase of LTP has been shown to require BDNF (12–14), although the nature of this requirement varies depending on the induction protocol (15–18).”
From Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines (2008) · cites this paper as [16]
Cites
Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons
Frey, U., Huang, Y.-Y., & Kandel, E. R. (1993) · Science · doi:10.1126/science.8389057 · Cited by 1,218 · see citing works
Intracellular injections of EGTA block induction of hippocampal long-term potentiation
Lynch, G., Larson, J., Kelso, S., Barrionuevo, G., & Schottler, F. (1983) · Nature · doi:10.1038/305719a0 · Cited by 1,116 · see citing works
Ernfors, P., Wetmore, C., Olson, L., & Persson, H. (1990) · Neuron · doi:10.1016/0896-6273(90)90090-3 · Cited by 819 · see citing works
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 · see citing works
Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events
Larson, J., & Lynch, G. (1986) · Science · doi:10.1126/science.3704635 · Cited by 597 · cited 1× · see citing works
“We confirmed frequency stimulation (pairing; Bliss and Lomo, 1973; Larson and Lynch, 1986; Gustafsson et al., 1987).”
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 · cited 1× · see citing works
“The pattern of decaying potentiation evident in the 1995; Figurov et al., 1996; Korte et al., 1996; Patterson et al., 1996).”
Blockade of Endogenous Ligands of TrkB Inhibits Formation of Ocular Dominance Columns
Cabelli, R. J., Shelton, D. L., Segal, R. A., & Shatz, C. J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80348-7 · Cited by 306 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · see citing works
Neurotrophin regulation of neural circuit development and function
Park, H., & Poo, M.-M. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3379 · Cited by 2,060 · see citing works
Neurotrophins as synaptic modulators
Poo, M.-M. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049004 · Cited by 1,775 · see citing works
Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition
Vaynman, S., Ying, Z., & Gomez‐Pinilla, F. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03720.x · Cited by 1,460 · see citing works
BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity
Kowiański, P., Lietzau, G., Czuba, E., Waśkow, M., Steliga, A., & Moryś, J. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0510-4 · Cited by 1,359 · see citing works
NEUROTROPHINS AND SYNAPTIC PLASTICITY
McAllister, A. K., Katz, L. C., & Lo, D. C. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.295 · Cited by 1,337 · see citing works
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193 · see citing works
Cleavage of proBDNF by tPA/Plasmin Is Essential for Long-Term Hippocampal Plasticity
Pang, P. T., Teng, H. K., Zaitsev, E., Woo, N. T., Sakata, K., Zhen, S., Teng, K. K., Yung, W.-H., Hempstead, B. L., & Lu, B. (2004) · Science · doi:10.1126/science.1100135 · Cited by 1,136 · see citing works
TrkB signalling pathways in LTP and learning
Minichiello, L. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2738 · Cited by 1,055 · see citing works
BDNF and synaptic plasticity, cognitive function, and dysfunction
Lu, B., Nagappan, G., & Lu, Y. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_9 · Cited by 1,043 · see citing works
BDNF and Activity-Dependent Synaptic Modulation: Figure 1.
Lu, B. (2003) · Learning & Memory · doi:10.1101/lm.54603 · Cited by 945 · see citing works
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., et al. (1999) · Nature Neuroscience · doi:10.1038/6374 · Cited by 946 · see citing works
Murer, M. G., Yan, Q., & Raisman-Vozari, R. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00014-9 · Cited by 874 · see citing works
Farmer, J., Zhao, X., van Praag, H., Wodtke, K., Gage, F. H., & Christie, B. R. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.09.029 · Cited by 836 · see citing works
BDNF regulates eating behavior and locomotor activity in mice
Kernie, S. G., Liebl, D. J., & Parada, L. F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.6.1290 · Cited by 806 · see citing works
Ying, S.-W., Futter, M., Rosenblum, K., Webber, M. J., Hunt, S. P., Bliss, T. V. P., & Bramham, C. R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01532.2002 · Cited by 784 · see citing works
Postsynaptic BDNF‐TrkB signaling in synapse maturation, plasticity, and disease
Yoshii, A., & Constantine‐Paton, M. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20765 · Cited by 744 · see citing works
Identification of a Signaling Pathway Involved in Calcium Regulation of BDNF Expression
Shieh, P. B., Hu, S.-C., Bobb, K., Timmusk, T., & Ghosh, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)81011-9 · Cited by 693 · see citing works
Antidepressant drugs act by directly binding to TRKB neurotrophin receptors
Casarotto, P. C., Girych, M., Fred, S. M., Kovaleva, V., Moliner, R., Enkavi, G., Biojone, C., Cannarozzo, C., Sahu, M. P., Kaurinkoski, K., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.034 · Cited by 663 · see citing works
Bekinschtein, P., Cammarota, M., Igaz, L. M., Bevilaqua, L. R. M., Izquierdo, I., & Medina, J. H. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.025 · Cited by 633 · see citing works
Dynamic visualization of local protein synthesis in hippocampal neurons
Aakalu, G., Smith, W. B., Nguyen, N., Jiang, C., & Schuman, E. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00295-1 · Cited by 611 · see citing works
Self-citationProtein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines
Tanaka, J.-I., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Science · doi:10.1126/science.1152864 · Cited by 615 · see citing works
Wang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., et al. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03058-x · Cited by 527 · see citing works
Mechanism of TrkB-Mediated Hippocampal Long-Term Potentiation
Minichiello, L., Calella, A. M., Medina, D. L., Bonhoeffer, T., Klein, R., & Korte, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00942-x · Cited by 506 · see citing works
BDNF and Hippocampal Synaptic Plasticity
Leal, G., Bramham, C. R., & Duarte, C. B. (2017) · Vitamins and Hormones · doi:10.1016/bs.vh.2016.10.004 · Cited by 425 · see citing works
Levine, E. S., Crozier, R. A., Black, I. B., & Plummer, M. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10235 · Cited by 412 · see citing works
Vaynman, S., Ying, Z., & Gomez-Pinilla, F. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.001 · Cited by 396 · see citing works
Adachi, M., Barrot, M., Autry, A. E., Theobald, D., & Monteggia, L. M. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.09.019 · Cited by 380 · see citing works
BDNF mechanisms in late LTP formation: A synthesis and breakdown
Panja, D., & Bramham, C. R. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.024 · Cited by 336 · see citing works
Autocrine BDNF-TrkB signalling within a single dendritic spine
Harward, S. C., Hedrick, N. G., Hall, C. E., Parra-Bueno, P., Milner, T. A., Pan, E., Laviv, T., Hempstead, B. L., Yasuda, R., & McNamara, J. O. (2016) · Nature · doi:10.1038/nature19766 · Cited by 325 · see citing works
Neurobiology of local and intercellular BDNF signaling
Sasi, M., Vignoli, B., Canossa, M., & Blum, R. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1964-4 · Cited by 324 · see citing works
Alonso, M., Vianna, M. R. M., Depino, A. M., Mello e Souza, T., Pereira, P., Szapiro, G., Viola, H., Pitossi, F., Izquierdo, I., & Medina, J. H. (2002) · Hippocampus · doi:10.1002/hipo.10035 · Cited by 339 · see citing works
Bourne, J. N., & Harris, K. M. (2011) · Hippocampus · doi:10.1002/hipo.20768 · Cited by 318 · see citing works
Role of the brain‐derived neurotrophic factor at glutamatergic synapses
Carvalho, A. L., Caldeira, M. V., Santos, S. D., & Duarte, C. B. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707509 · Cited by 290 · see citing works
Larson, J., & Munkácsy, E. (2015) · Brain Research · doi:10.1016/j.brainres.2014.10.034 · Cited by 285 · see citing works
Noble, E. E., Billington, C. J., Kotz, C. M., & Wang, C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00776.2010 · Cited by 284 · see citing works
Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning
Catlow, B. J., Song, S., Paredes, D. A., Kirstein, C. L., & Sanchez-Ramos, J. (2013) · Experimental Brain Research · doi:10.1007/s00221-013-3579-0 · Cited by 266 · see citing works
Corticosterone effects on BDNF expression in the hippocampus. Implications for memory formation
Schaaf, M. J. M., De Kloet, E. R., & Vreugdenhil, E. (2000) · Stress · doi:10.3109/10253890009001124 · Cited by 270 · see citing works
Neurotrophin-evoked depolarization requires the sodium channel NaV1.9
Blum, R., Kafitz, K. W., & Konnerth, A. (2002) · Nature · doi:10.1038/nature01085 · Cited by 266 · see citing works
Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity.
Edelmann, E., Leßmann, V., & Brigadski, T. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.043 · Cited by 248 · see citing works
BDNF activates mTOR to regulate GluR1 expression required for memory formation
Slipczuk, L., Bekinschtein, P., Katche, C., Cammarota, M., Izquierdo, I., & Medina, J. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006007 · Cited by 246 · see citing works
Form follows function: BDNF and its involvement in sculpting the function and structure of synapses
Zagrebelsky, M., & Korte, M. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.029 · Cited by 241 · see citing works
LTP consolidation: Substrates, explanatory power, and functional significance
Lynch, G., Rex, C. S., & Gall, C. M. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.027 · Cited by 214 · see citing works
Suppression of hippocampal plasticity‐related gene expression by sleep deprivation in rats
Guzman‐Marin, R., Ying, Z., Suntsova, N., Methippara, M., Bashir, T., Szymusiak, R., Gomez‐Pinilla, F., & McGinty, D. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.115287 · Cited by 206 · see citing works
Exercise induces BDNF and synapsin I to specific hippocampal subfields
Vaynman, S., Ying, Z., & Gómez‐Pinilla, F. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20077 · Cited by 203 · see citing works
Exercise augmentation of exposure therapy for PTSD: rationale and pilot efficacy data
Powers, M. B., Medina, J. L., Burns, S., Kauffman, B. Y., Monfils, M., Asmundson, G. J. G., Diamond, A., McIntyre, C., & Smits, J. A. J. (2015) · Cognitive Behaviour Therapy · doi:10.1080/16506073.2015.1012740 · Cited by 194 · see citing works
Du, J., Feng, L., Yang, F., & Lu, B. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.6.1423 · Cited by 178 · see citing works
Evers, M. R., Salmen, B., Bukalo, O., Rollenhagen, A., Bösl, M. R., Morellini, F., Bartsch, U., Dityatev, A., & Schachner, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-16-07177.2002 · Cited by 172 · see citing works
Koponen, E., Võikar, V., Riekki, R., Saarelainen, T., Rauramaa, T., Rauvala, H., Taira, T., & Castrén, E. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.01.006 · Cited by 170 · see citing works
Wibrand, K., Messaoudi, E., Håvik, B., Steenslid, V., Løvlie, R., Steen, V. M., & Bramham, C. R. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04687.x · Cited by 153 · see citing works
Deprived of habitual running, rats downregulate BDNF and TrkB messages in the brain
Widenfalk, J., Olson, L., & Thorén, P. (1999) · Neuroscience Research · doi:10.1016/s0168-0102(99)00051-6 · Cited by 156 · see citing works
Molecular Mechanisms of Early and Late LTP
Baltaci, S. B., Mogulkoc, R., & Baltaci, A. K. (2019) · Neurochemical Research · doi:10.1007/s11064-018-2695-4 · Cited by 152 · see citing works
Panja, D., Kenney, J. W., D’Andrea, L., Zalfa, F., Vedeler, A., Wibrand, K., Fukunaga, R., Bagni, C., Proud, C. G., & Bramham, C. R. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.016 · Cited by 143 · see citing works
Shulga, A., Thomas-Crusells, J., Sigl, T., Blaesse, A., Mestres, P., Meyer, M., Yan, Q., Kaila, K., Saarma, M., Rivera, C., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5268-07.2008 · Cited by 137 · see citing works
The Biological Functions and Signaling Mechanisms of the p75 Neurotrophin Receptor
Kraemer, B. R., Yoon, S. O., & Carter, B. D. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_6 · Cited by 125 · see citing works
BDNF in the dentate gyrus is required for consolidation of “pattern-separated” memories.
Bekinschtein, P., Kent, B. A., Oomen, C. A., Clemenson, G. D., Gage, F. H., Saksida, L. M., & Bussey, T. J. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.027 · Cited by 124 · see citing works
Banerjee, R., Ghosh, A. K., Ghosh, B., Bhattacharyya, S., & Mondal, A. C. (2013) · Clinical Medicine Insights: Pathology · doi:10.4137/cpath.s12530 · Cited by 135 · see citing works
Deciphering Proneurotrophin Actions
Hempstead, B. L. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-45106-5_2 · Cited by 106 · see citing works
Alme, M. N., Wibrand, K., Dagestad, G., & Bramham, C. R. (2007) · Neural Plasticity · doi:10.1155/2007/26496 · Cited by 103 · see citing works
Cazorla, M., Jouvenceau, A., Rose, C., Guilloux, J.-P., Pilon, C., Dranovsky, A., & Prémont, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009777 · Cited by 99 · see citing works
Neurotrophic Factors and Their Potential Applications in Tissue Regeneration
Xiao, N., & Le, Q.-T. (2016) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-015-0376-4 · Cited by 93 · see citing works
Remondes, M., & Schuman, E. M. (2003) · Learning & Memory · doi:10.1101/lm.59103 · Cited by 81 · see citing works
Self-citationCheng, Q., & Yeh, H. H. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.037846 · Cited by 73 · see citing works
The requirement of BDNF for hippocampal synaptic plasticity is experience‐dependent
Aarse, J., Herlitze, S., & Manahan‐Vaughan, D. (2016) · Hippocampus · doi:10.1002/hipo.22555 · Cited by 74 · see citing works
Bramham, C. R. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)63025-8 · Cited by 69 · see citing works
Wang, Y., Qi, J.-S., Kong, S., Sun, Y., Fan, J., Jiang, M., & Chen, G. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.04.007 · Cited by 39 · see citing works
Ozawa, T., Yamada, K., & Ichitani, Y. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.01.034 · Cited by 31 · see citing works
- Authors
- Kang, H., Welcher, A. A., Shelton, D., & Schuman, E. M.
- Affiliations
- California Institute of Technology (US)
- Amgen (United States) (US)
- Genentech (US)
- Corresponding author
- Schuman, Erin M
- ORCID
- Schuman, Erin M
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1997-09
- Volume
- 19
- Issue
- 3
- Pages
- 653-664
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2023390598
- Cited by
- 481
- References
- 7
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 18 · 2017: 7 · 2016: 22 · 2015: 16 · 2014: 25 · 2013: 23 · 2012: 11
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- California Institute of Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neurotrophins, TrkB signaling, hippocampal long-term potentiation, theta burst stimulation, pairing, late-phase LTP, synaptic plasticity, synaptic transmission
- MeSH terms
- Animals, Antibody Specificity, Binding, Competitive, Electrophysiology, Hippocampus, Immunoglobulin G, Male, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Rabbits, Time Factors, Signal Transduction, Gene Expression, 3T3 Cells, Rats, Sprague-Dawley, Receptors, Nerve Growth Factor, Long-Term Potentiation, Brain-Derived Neurotrophic Factor, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Mice, Rats
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