Cited by 506Neuroscience and Neuropharmacology ResearchNerve injury and regenerationMemory and Neural Mechanisms

Mechanism of TrkB-Mediated Hippocampal Long-Term Potentiation

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Minichiello, Liliana, Calella, Anna Maria, Medina, Diego L., Bonhoeffer, Tobias, Klein, Rüdiger, Korte, Martin·2002·Neuron

Abstract

The TrkB receptor tyrosine kinase and its ligand, BDNF, have an essential role in certain forms of synaptic plasticity. However, the downstream pathways required to mediate these functions are unknown. We have studied mice with a targeted mutation in either the Shc or the phospholipase Cgamma (PLCgamma) docking sites of TrkB (trkB(SHC/SHC) and trkB(PLC/PLC) mice). We found that hippocampal long-term potentiation was impaired in trkB(PLC/PLC) mice, but not trkB(SHC/SHC) mice. BDNF stimulation of primary neurons derived from trkB(PLC/PLC) mice fully retained their ability to activate MAP kinases, whereas induction of CREB and CaMKIV phosphorylation was strongly impaired. The opposite effect was observed in trkB(SHC/SHC) neurons, suggesting that MAPKs and CREB act in parallel pathways. Our results provide genetic evidence that TrkB mediates hippocampal plasticity via recruitment of PLCgamma, and by subsequent phosphorylation of CaMKIV and CREB.

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  • Deletion of the tyrosine residue in TrkB mediating PLCγ signaling disrupts LTP.

    “These effects appear to be specifically mediated by signaling through the phospholipase Cγ (PLCγ) signaling pathway, since deletion of the tyrosine residue in TrkB mediating this signaling disrupts LTP79.”
  • TrkB effects on LTP are specifically mediated by PLCγ signaling.

    “These effects appear to be specifically mediated by signaling through the phospholipase Cγ (PLCγ) signaling pathway, since deletion of the tyrosine residue in TrkB mediating this signaling disrupts LTP79.”

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Authors
Minichiello, L., Calella, A. M., Medina, D. L., Bonhoeffer, T., Klein, R., & Korte, M.
Affiliations
  • European Molecular Biology Laboratory (IT)
  • Max Planck Society (DE)
Corresponding author
Minichiello, Liliana
Venue
Neuron
Publisher
Elsevier BV
Published
2002-09
Volume
36
Issue
1
Pages
121-137
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1966100684
Cited by
506
References
63
Citations by year
2026: 9 · 2025: 11 · 2024: 28 · 2023: 18 · 2022: 22 · 2021: 27 · 2020: 18 · 2019: 21 · 2018: 20 · 2017: 23 · 2016: 23 · 2015: 20 · 2014: 23 · 2013: 30 · 2012: 23
FWCI
7.32
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
European Commission
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
TrkB receptor, brain-derived neurotrophic factor, hippocampal long-term potentiation, synaptic plasticity, phospholipase C-gamma, Shc adaptor protein, MAPK signaling, CREB phosphorylation, parallel signaling pathways
MeSH terms
Src Homology 2 Domain-Containing, Transforming Protein 1, Animals, Binding Sites, DNA-Binding Proteins, Fetus, Hippocampus, Isoenzymes, Mice, Transgenic, Mutation, Neurons, Type C Phospholipases, Proteins, Transcription Factors, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Immediate-Early Proteins, Brain-Derived Neurotrophic Factor, Receptor, trkB, Mitogen-Activated Protein Kinases, Active Transport, Cell Nucleus, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Mice, Early Growth Response Protein 1, Phospholipase C gamma, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Shc Signaling Adaptor Proteins

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