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The Journal of Neuroscience, June 15, 2005, 25(24):5796-5802; doi:10.1523/JNEUROSCI.0824-05.2005

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Development/Plasticity/Repair
Endogenous Neurotrophins Are Required for the Induction of GABAergic Long-Term Potentiation in the Neonatal Rat Hippocampus

Paolo Gubellini,¹ Yehezkel Ben-Ari,² and Jean-Luc Gaïarsa²

¹Laboratoire "Interactions Cellulaires, Neurodégénérescence et Neuroplasticité," Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6186, 13402 Marseille Cedex 20, France, and ²Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale Unité 29, 13273 Marseille Cedex 09, France

In the developing rat hippocampus, GABAergic synapses undergo a Ca²⁺-dependent long-term potentiation (LTP_GABA-A); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA_A receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP_GABA-A. The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP_GABA-A, whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP_GABA-A. On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP_GABA-A, whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

Key words: BDNF; development; k-252a; Lavendustin A; neurotrophins; protein tyrosine kinase; synaptic plasticity

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Received Aug 4, 2004; revised May 10, 2005; accepted May 14, 2005.

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