The cellular and synaptic location of activated TrkB in mouse hippocampus during limbic epileptogenesis
Open accessAbstract
Understanding the mechanisms of limbic epileptogenesis in cellular and molecular terms may provide novel therapeutic targets for its prevention. The neurotrophin receptor tropomyosin-related kinase B (TrkB) is thought to be critical for limbic epileptogenesis. Enhanced activation of TrkB, revealed by immunodetection of enhanced phosphorylated TrkB (pTrkB), a surrogate measure of its activation, has been identified within the hippocampus in multiple animal models. Knowledge of the cellular locale of activated TrkB is necessary to elucidate its functional consequences. Using an antibody selective to pTrkB in conjunction with confocal microscopy and cellular markers, we determined the cellular and subcellular locale of enhanced pTrkB induced by status epilepticus (SE) evoked by infusion of kainic acid into the amygdala of adult mice. SE induced enhanced pTrkB immunoreactivity in two distinct populations of principal neurons within the hippocampus-the dentate granule cells and CA1 pyramidal cells. Enhanced immunoreactivity within granule cells was found within mossy fiber axons and giant synaptic boutons. By contrast, enhanced immunoreactivity was found within apical dendritic shafts and spines of CA1 pyramidal cells. A common feature of this enhanced pTrkB at these cellular locales is its localization to excitatory synapses between excitatory neurons, presynaptically in the granule cells and postsynaptically in CA1 pyramidal cells. Long-term potentiation (LTP) is one cellular consequence of TrkB activation at these excitatory synapses that may promote epileptogenesis.
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Limbic epileptogenesis involves a partially-understood molecular cascade that results in aberrant neuronal connectivity and chronic recurrent spontaneous seizures.
“Development of TLE or limbic epileptogenesis [4, 5] involves a partially-understood molecular cascade [6] that results in aberrant neuronal connectivity [7, 8] from a multi-architecture neuronal network of the limbic system connected to hippocampal formation [9] that contributes to a systemic process in the brain that leads to chronic recurrent spontaneous seizures [10].”
From Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1 (2015) · cites this paper as [5]
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Cites
Abràmoff, M. D., Magalhães, P. J., & Ram, S. J. (2004) · Utrecht University Repository (Utrecht University) · Cited by 11,816 · see citing works
Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP
Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042 · see citing works
The distribution of tau in the mammalian central nervous system.
Binder, L. I., Frankfurter, A., & Rebhun, L. I. (1985) · The Journal of cell biology · doi:10.1083/jcb.101.4.1371 · Cited by 1,588 · see citing works
Epilepsy: A Comprehensive Textbook
Vaughn, B. V. (1998) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-199805000-00039 · Cited by 1,390 · see citing works
Conner, J. M., Lauterborn, J. C., Yan, Q., Gall, C. M., & Varon, S. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-07-02295.1997 · Cited by 1,097 · 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 Activity-Dependent Synaptic Modulation: Figure 1.
Lu, B. (2003) · Learning & Memory · doi:10.1101/lm.54603 · Cited by 945 · see citing works
Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat
Ishizuka, N., Weber, J., & Amaral, D. G. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.902950407 · Cited by 899 · see citing works
Essential Role for TrkB Receptors in Hippocampus-Mediated Learning
Minichiello, L., Korte, M., Wolfer, D., Kühn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Lipp, H.-P., Bonhoeffer, T., & Klein, R. (1999) · Neuron · doi:10.1016/s0896-6273(00)80853-3 · Cited by 799 · see citing works
Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons
Verkhratsky, A. (2004) · Physiological Reviews · doi:10.1152/physrev.00004.2004 · Cited by 709 · see citing works
Synaptic plasticity at hippocampal mossy fibre synapses
Nicoll, R. A., & Schmitz, D. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1786 · Cited by 653 · see citing works
Amaral, D. G., & Dent, J. A. (1981) · The Journal of Comparative Neurology · doi:10.1002/cne.901950106 · Cited by 606 · see citing works
Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene.
Cole, T., Wenzel, H., Kafer, K. E., Schwartzkroin, P., & Palmiter, R. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.4.1716 · Cited by 560 · see citing works
Löscher, W. (2002) · Epilepsy Research · doi:10.1016/s0920-1211(02)00073-6 · Cited by 510 · see citing works
Schauwecker, P. E., & Steward, O. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4103 · Cited by 510 · 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
Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system
Yan, Q., Rosenfeld, R. D., Matheson, C. R., Hawkins, N., Lopez, O. T., Bennett, L., & Welcher, A. A. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00613-6 · Cited by 498 · see citing works
Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions
VanLandingham, K., Heinz, E. R., Cavazos, J. E., & Lewis, D. V. (1998) · Annals of Neurology · doi:10.1002/ana.410430403 · Cited by 444 · see citing works
Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice
Lehnart, S. E., Mongillo, M., Bellinger, A. M., Lindegger, N., Chen, B.-X., HSUEH, W. H., Reiken, S. R., Wronska, A., Drew, L., Ward, C. W., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35346 · Cited by 413 · see citing works
Huber, G., & Matus, A. I. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-01-00151.1984 · Cited by 326 · see citing works
Croll, S. D., Suri, C., Compton, D. L., Simmons, M. V., Yancopoulos, G. D., Lindsay, R. M., Wiegand, S. J., Rudge, J., & Scharfman, H. E. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00296-1 · Cited by 310 · see citing works
Conditional Deletion of TrkB but Not BDNF Prevents Epileptogenesis in the Kindling Model
He, X.-P., Kotloski, R. J., Nef, S., Luikart, B. W., Parada, L. F., & McNamara, J. O. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.019 · Cited by 304 · see citing works
Self-citationMultiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism
Yeckel, M. F., Kapur, A., & Johnston, D. (1999) · Nature Neuroscience · doi:10.1038/10180 · Cited by 295 · see citing works
Zinc-Mediated Transactivation of TrkB Potentiates the Hippocampal Mossy Fiber-CA3 Pyramid Synapse
Huang, Y. Z., Pan, E., Xiong, Z., & McNamara, J. O. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.026 · Cited by 275 · see citing works
Self-citationWatson, F. L., Heerssen, H. M., Moheban, D. B., Lin, M. Z., Sauvageot, C. M., Bhattacharyya, A., Pomeroy, S. L., & Segal, R. A. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07889.1999 · Cited by 272 · see citing works
Suppressed Epileptogenesis in BDNF Mutant Mice
Kokaia, M., Ernfors, P., Kokaia, Z., Elmér, E., Jaenisch, R., & Lindvall, O. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1024 · Cited by 271 · see citing works
The risk of epilepsy following febrile convulsions
Annegers, J. F., Hauser, W. A., Elveback, L. R., et al. (1979) · Neurology · doi:10.1212/wnl.29.3.297 · Cited by 256 · see citing works
Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice
Li, T., Ren, G., Lusardi, T. A., Wilz, A., Lan, J. Q., Iwasato, T., Itohara, S., Simon, R. P., & Boison, D. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33737 · Cited by 251 · see citing works
Qian, J., & Noebels, J. L. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.089276 · Cited by 201 · see citing works
Li, H., Armando, I., Yu, P., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33637c1 · Cited by 190 · see citing works
Walter, C., Murphy, B. L., Pun, R. Y. K., Spieles-Engemann, A. L., & Danzer, S. C. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0431-07.2007 · Cited by 189 · see citing works
Binder, D. K., Routbort, M. J., & McNamara, J. O. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04616.1999 · Cited by 188 · see citing works
Self-citationPan, E., Zhang, X., Huang, Z., Krężel, A., Zhao, M., Tinberg, C. E., Lippard, S. J., & McNamara, J. O. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.019 · Cited by 187 · see citing works
Self-citationTrk Receptors Function As Rapid Retrograde Signal Carriers in the Adult Nervous System
Bhattacharyya, A., Watson, F. L., Bradlee, T. A., Pomeroy, S. L., Stiles, C. D., & Segal, R. A. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-18-07007.1997 · Cited by 182 · see citing works
Sayın, Ü., Osting, S., Hagen, J., Rutecki, P. A., & Sutula, T. P. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02759.2003 · Cited by 166 · see citing works
Binder, D. K., Routbort, M. J., RYAN, T. E., Yancopoulos, G. D., & McNamara, J. O. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-04-01424.1999 · Cited by 163 · see citing works
Self-citationDifferential Utilization of Trk Autophosphorylation Sites
Segal, R. A., Bhattacharyya, A., Rua, L. A., Alberta, J. A., Stephens, R. M., Kaplan, D. R., & Stiles, C. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.33.20175 · Cited by 160 · see citing works
Mouri, G., Jimenez-Mateos, E. M., Engel, T., Dunleavy, M., Hatazaki, S., Paucard, A., Matsushima, S., Taki, W., & Henshall, D. C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.061 · Cited by 149 · see citing works
The cholinergic system, nerve growth factor and the cytoskeleton
Niewiadomska, G., Mietelska‐Porowska, A., & Mazurkiewicz, M. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.02.024 · Cited by 142 · see citing works
TrkB as a Potential Synaptic and Behavioral Tag
Lü, Y., Ji, Y., Ganesan, S., Schloesser, R. J., Martinowich, K., Sun, M., Mei, F., Chao, M. V., & Lu, B. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2707-11.2011 · Cited by 130 · see citing works
Facilitation of kindling by prior induction of long-term potentiation in the perforant path
Sutula, T. P., & Steward, O. (1987) · Brain Research · doi:10.1016/0006-8993(87)90245-9 · Cited by 123 · see citing works
Intradentate colchicine retards the development of amygdala kindling
Dasheiff, R. M., & McNamara, J. O. (1982) · Annals of Neurology · doi:10.1002/ana.410110405 · Cited by 114 · see citing works
Self-citationXu, B., Michalski, B., Racine, R. J., & Fahnestock, M. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.044 · Cited by 100 · see citing works
Gruart, A., Sciarretta, C., Valenzuela‐Harrington, M., Delgado-Garcia, J. M., & Minichiello, L. (2007) · Learning & Memory · doi:10.1101/lm.428307 · Cited by 97 · see citing works
Spencer-Segal, J. L., Waters, E. M., Bath, K. G., Chao, M. V., McEwen, B. S., & Milner, T. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0910-11.2011 · Cited by 92 · see citing works
Danzer, S. C., & McNamara, J. O. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3846-04.2004 · Cited by 90 · see citing works
Self-citationIs Refractory Epilepsy Preventable?
Arroyo, S., Brodie, M. J., AVANZINI, G., Baumgartner, C., Chiron, C., Dulac, O., French, J. A., & Serratosa, J. M. (2002) · Epilepsia · doi:10.1046/j.1528-1157.2002.38501.x · Cited by 90 · see citing works
Metaplasticity of Mossy Fiber Synaptic Transmission Involves Altered Release Probability
Goussakov, I. V., Fink, K., Elger, C. E., & Beck, H. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03434.2000 · Cited by 88 · see citing works
Savage, D., Rigsbee, L., & McNamara, J. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-02-00408.1985 · Cited by 83 · see citing works
Self-citationHe, X., Minichiello, L., Klein, R., & McNamara, J. O. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-17-07502.2002 · Cited by 82 · see citing works
Self-citationCharacterization of neuronal death induced by focally evoked limbic seizures in the C57BL/6 mouse
Araki, T., Simon, R. P., Taki, W., Lan, J., & Henshall, D. C. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10356 · Cited by 79 · see citing works
Disruption of TrkB-Mediated Phospholipase Cγ Signaling Inhibits Limbic Epileptogenesis
He, X. P., Pan, E., Sciarretta, C., Minichiello, L., & McNamara, J. O. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5821-09.2010 · Cited by 76 · see citing works
Self-citationsAPPα antagonizes dendritic degeneration and neuron death triggered by proteasomal stress
Copanaki, E., Chang, S., Vlachos, A., Tschäpe, J., Müller, U., Kögel, D., & Deller, T. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.04.007 · Cited by 74 · see citing works
Mutual Regulation of Src Family Kinases and the Neurotrophin Receptor TrkB
Huang, Y. Z., & McNamara, J. O. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.091041 · Cited by 69 · see citing works
Self-citationLearning induces neurotrophin signaling at hippocampal synapses
Chen, L. Y., Rex, C. S., Sanaiha, Y., LYNCH, G. S., & Gall, C. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912973107 · Cited by 66 · see citing works
Danzer, S. C., Kotloski, R. J., Walter, C., Hughes, M., & McNamara, J. O. (2008) · Hippocampus · doi:10.1002/hipo.20426 · Cited by 64 · see citing works
Self-citationShimizu, H., Fukaya, M., Yamasaki, M., Watanabe, M., Manabe, T., & Kamiya, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802175105 · Cited by 62 · see citing works
Factors predictive of outcome in patients with de novo status epilepticus
Tsai, M., Chuang, Y., Chang, H.-W., Chang, W.-N., Lai, S.-K., Huang, C.-R., Tsai, N., Wang, H.-F., Lin, Y.-J., & Lu, C.-H. (2008) · QJM · doi:10.1093/qjmed/hcn149 · Cited by 56 · see citing works
Kainate receptors and the induction of mossy fibre long-term potentiation
Bortolotto, Z. A., Lauri, S. E., Isaac, J. T. R., & Collingridge, G. L. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2002.1216 · Cited by 51 · see citing works
The apical shaft of CA1 pyramidal cells is under GABAergic interneuronal control
Papp, E., Leinekugel, X., Henze, D. A., Lee, J. D., & Buzsáki, G. (2001) · Neuroscience · doi:10.1016/s0306-4522(00)00584-4 · Cited by 46 · see citing works
Dunleavy, M., Shinoda, S., Schindler, C. K., Ewart, C., Dolan, R. D., Gobbo, O. L., Kerskens, C., & Henshall, D. C. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090119 · Cited by 44 · see citing works
Danzer, S. C., He, X., & McNamara, J. O. (2004) · Hippocampus · doi:10.1002/hipo.10190 · Cited by 43 · see citing works
Self-citationBDNF Signaling during Learning Is Regionally Differentiated within Hippocampus
Chen, L. Y., Rex, C. S., Pham, D. T., LYNCH, G. S., & Gall, C. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3549-10.2010 · Cited by 40 · see citing works
Shc-binding site in the TrkB receptor is not required for hippocampal long-term potentiation
Körte, M., Minichiello, L., Klein, R., & Bonhoeffer, T. (2000) · Neuropharmacology · doi:10.1016/s0028-3908(99)00273-7 · Cited by 37 · see citing works
Differences in two mice strains on kainic acid-induced amygdalar seizures
Kasugai, M., 赤池, 浩., Imamura, S.-I., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.067 · Cited by 29 · see citing works
Merchenthaler (1999) · doi:10.1002/(sici)1096-9861(19990111)403:2
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- Authors
- Helgager, J., Liu, G., & McNamara, J. O.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- Corresponding author
- McNamara, James O.
- ORCID
- McNamara, James O.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2012-12-17
- Volume
- 521
- Issue
- 3
- Pages
- 499-521
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC3527653
- OpenAlex
- W2015799055
- Cited by
- 17
- References
- 66
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM008441)
- National Institute of Neurological Disorders and Stroke (R01NS056217, NS056217)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- TrkB, status epilepticus, kainic acid, hippocampus, dentate gyrus granule cells, CA1 pyramidal neurons, excitatory synapses, synaptic localization, long-term potentiation, neurotrophin receptors, amygdala, dendritic spines
- MeSH terms
- Animals, Disease Models, Animal, Female, Immunohistochemistry, Kainic Acid, Limbic System, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, Pilocarpine, Protein-Tyrosine Kinases, Status Epilepticus, Synapses, Long-Term Potentiation, Pyramidal Cells, Excitatory Amino Acid Agonists, Muscarinic Agonists, Dentate Gyrus, Mossy Fibers, Hippocampal, Receptor, trkB, Green Fluorescent Proteins, Mice, CA1 Region, Hippocampal
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