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The Journal of Neuroscience, March 29, 2006, 26(13):3496-3504; doi:10.1523/JNEUROSCI.3792-05.2006

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Development/Plasticity/Repair
Hippocampal Long-Term Potentiation Is Supported by Presynaptic and Postsynaptic Tyrosine Receptor Kinase B-Mediated Phospholipase C Signaling

Annette Gärtner,^1 * Dorit G. Polnau,^1 * Volker Staiger,¹ Carla Sciarretta,² Liliana Minichiello,² Hans Thoenen,¹ Tobias Bonhoeffer,¹ and Martin Korte^1,3

¹Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany, and ²European Molecular Biology Laboratory, Mouse Biology Programme, 00016 Monterotondo, Italy, and ³Technical University Braunschweig, Zoological Institute, 38106 Braunschweig, Germany

Correspondence should be addressed to Dr. Martin Korte, Technical University Braunschweig, Zoological Institute, Mendelssohnstrasse 4, 38106 Braunschweig, Germany. Email: m.korte{at}tu-bs.de

Neurotrophins have been shown to play a critical role in activity-dependent synaptic plasticity such as long-term potentiation (LTP) in the hippocampus. Although the role of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor [tyrosine receptor kinase B (TrkB)] is well documented, it still remains unresolved whether presynaptic or postsynaptic activation of TrkB is involved in the induction of LTP. To address this question, we locally and specifically interfered with a downstream target of the TrkB receptor, phospholipase C (PLC). We prevented PLC signaling by overexpression of the PLC pleckstrin homology (PH) domain with a Sindbis virus vector. The isolated PH domain has an inhibitory effect and thereby blocks endogenous PLC signaling and consequently also IP₃ production. Surprisingly, concurrent presynaptic and postsynaptic blockade of PLC signaling was required to reduce LTP to levels comparable with those in TrkB and BDNF knock-out mice. Blockade of presynaptic or postsynaptic signaling alone did not result in a significant reduction of LTP.

Key words: synaptic plasticity; hippocampus; long-term potentiation; neurotrophins; neurotrophin receptors; intracellular signaling

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Received Sept. 8, 2005; revised Jan. 4, 2006; accepted Jan. 22, 2006.

Correspondence should be addressed to Dr. Martin Korte, Technical University Braunschweig, Zoological Institute, Mendelssohnstrasse 4, 38106 Braunschweig, Germany. Email: m.korte{at}tu-bs.de

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