Some Forms of cAMP-Mediated Long-Lasting Potentiation Are Associated with Release of BDNF and Nuclear Translocation of Phospho-MAP Kinase
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Long-lasting forms of synaptic plasticity like the late phase of LTP (L-LTP) typically require an elevation of cAMP, the recruitment of the cAMP-dependent protein kinase (PKA), and ultimately the activation of transcription and translation; some forms also require brain-derived neurotrophic factor (BDNF). Both cAMP and BDNF can activate mitogen-activated protein kinase (MAPK/ERK), which also plays a role in LTP. However, little is known about the mechanisms whereby cAMP, BDNF, and MAPK interact. We find that increases in cAMP can rapidly activate the BDNF receptor TrkB and induce BDNF-dependent long-lasting potentiation at the Schaffer collateral-CA1 synapse in hippocampus. Surprisingly, in these BDNF-dependent forms of potentiation, which are also MAPK dependent, TrkB activation is not critical for the activation of MAPK but instead appears to modulate the subcellular distribution and nuclear translocation of the activated MAPK.
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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 [17]
Cites
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
Sweatt, J. D. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00054.x · Cited by 1,131 · see citing works
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 · see citing works
Martin, K. C., Michael, D., Rose, J. C., Barad, M., Casadio, A., Zhu, H., & Kandel, E. R. (1997) · Neuron · doi:10.1016/s0896-6273(00)80330-x · Cited by 545 · see citing works
Self-citationDepolarization and cAMP Elevation Rapidly Recruit TrkB to the Plasma Membrane of CNS Neurons
Meyer-Franke, A., Wilkinson, G. A., Kruttgen, A., Hu, M., Munro, E., Hanson, M. G., Reichardt, L. F., & Barres, B. A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80586-3 · Cited by 516 · see citing works
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Cited by
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Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms
Pittenger, C., & Duman, R. S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301574 · Cited by 1,795 · see citing works
Self-citationMAPK cascade signalling and synaptic plasticity
Thomas, G. M., & Huganir, R. L. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1346 · Cited by 1,454 · see citing works
Modelling schizophrenia using human induced pluripotent stem cells
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., et al. (2011) · Nature · doi:10.1038/nature09915 · Cited by 1,375 · 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
Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, M. J., Cao, L., Zuzga, D. S., Francis, J. S., Fitzsimons, H. L., Jiao, X., Bland, R. J., Klugmann, M., Banks, W. A., Drucker, D. J., et al. (2003) · Nature Medicine · doi:10.1038/nm919 · Cited by 851 · 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
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
Protein 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
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
Vaynman, S., & Gomez-Pinilla, F. (2005) · Neurorehabilitation and Neural Repair · doi:10.1177/1545968305280753 · Cited by 420 · 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
Vaynman, S., & Gomez‐Pinilla, F. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20979 · Cited by 299 · see citing works
Larson, J., & Munkácsy, E. (2015) · Brain Research · doi:10.1016/j.brainres.2014.10.034 · Cited by 285 · see citing works
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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
Ninan, I., Bath, K. G., Dagar, K., Perez-Castro, R., Plummer, M. R., Lee, F. S., & Chao, M. V. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1405-10.2010 · Cited by 180 · see citing works
Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder
Kapczinski, F., Frey, B. N., Kauer-Sant’Anna, M., & Grassi-Oliveira, R. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.7.1101 · Cited by 181 · see citing works
The Role of Extracellular Regulated Kinases I/II in Late-Phase Long-Term Potentiation
Rosenblum, K., Futter, M., Voss, K., Erent, M., Skehel, P. A., French, P., Obosi, L., Jones, M. W., & Bliss, T. V. P. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05432.2002 · Cited by 155 · 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
Tronson, N. C., Schrick, C., Guzman, Y. F., Huh, K. H., Srivastava, D. P., Penzes, P., Guedea, A. L., Gao, C., & Radulovic, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5619-08.2009 · Cited by 136 · 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
Sharma, S. K., Sherff, C. M., Shobe, J., Bagnall, M. W., Sutton, M. A., & Carew, T. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03899.2003 · Cited by 125 · see citing works
Disorders of memory and plasticity in psychiatric disease
Pittenger, C. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.4/cpittenger · Cited by 92 · see citing works
Self-citationCell biology of BDNF and its relevance to schizophrenia
Lu, B., & Martinowich, K. (2008) · Novartis Foundation Symposia · doi:10.1002/9780470751251.ch10 · Cited by 92 · see citing works
Neurotrophic factors in Parkinson’s disease are regulated by exercise: Evidence-based practice
da Silva, P. G. C., Domingues, D. D., de Carvalho, L. A., Allodi, S., & Correa, C. L. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.02.017 · Cited by 87 · 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
Smolen, P., Baxter, D. A., & Byrne, J. H. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.072470 · Cited by 61 · see citing works
Eggert, S., Kins, S., Endres, K., & Brigadski, T. (2022) · Biological Chemistry · doi:10.1515/hsz-2021-0330 · Cited by 46 · see citing works
Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp
Mariga, A., Glaser, J., Mathias, L., Xu, D., Xiao, M., Worley, P., Ninan, I., & Chao, M. V. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.064 · Cited by 45 · see citing works
CPEB4 knockout mice exhibit normal hippocampus-related synaptic plasticity and memory
Tsai, L.-Y., Chang, Y.-W., Lin, P.-Y., Chou, H.-J., Liu, T.-J., Lee, P.-T., Huang, W.-H., Tsou, Y.-L., & Huang, Y.-S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084978 · Cited by 35 · 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
Weng, W., Chen, Y., Wang, M., Zhuang, Y., & Behnisch, T. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00247 · Cited by 14 · see citing works
ERK signaling is required for eye-specific retino-geniculate segregation
Naska, S., Cenni, M. C., Menna, E., & Maffei, L. (2004) · Development · doi:10.1242/dev.01212 · Cited by 14 · see citing works
Stojanovic, T., Velarde Gamez, D., Schuld, G. J., Bormann, D., Cabatic, M., Uhrin, P., Lubec, G., & Monje, F. J. (2022) · Cells · doi:10.3390/cells11020261 · Cited by 8 · see citing works
- Authors
- Patterson, S. L., Pittenger, C., Morozov, A., Martin, K. C., Scanlin, H., Drake, C., & Kandel, E. R.
- Affiliations
- Columbia University (US)
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Cornell University (US)
- Corresponding author
- Kandel, Eric R
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 32
- Issue
- 1
- Pages
- 123-140
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2019438547
- Cited by
- 334
- References
- 5
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 11 · 2017: 8 · 2016: 15 · 2015: 9 · 2014: 24 · 2013: 13 · 2012: 9
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2t32gm008464-31)
- National Institute of General Medical Sciences (GM08464-05/06)
- 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
- cyclic AMP, brain-derived neurotrophic factor, TrkB receptor, MAPK/ERK pathway, nuclear translocation, synaptic plasticity, long-term potentiation, Schaffer collateral-CA1 synapses, hippocampus, protein kinase A
- MeSH terms
- Cyclic AMP, Animals, Cell Nucleus, Dendrites, Colforsin, Ligands, Membrane Potentials, Mice, Inbred BALB C, Mice, Inbred C57BL, Neuronal Plasticity, Phosphorylation, Theta Rhythm, Microscopy, Immunoelectron, Presynaptic Terminals, Long-Term Potentiation, Mice, Knockout, Brain-Derived Neurotrophic Factor, Excitatory Postsynaptic Potentials, Receptor, trkB, Mitogen-Activated Protein Kinases, Active Transport, Cell Nucleus, Mice
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