Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.
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.
Gubellini
Paolo
P
Laboratoire Interactions Cellulaires, Neurodégénérescence et Neuroplasticité, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6186, 13402 Marseille Cedex 20, France. paolo.gubellini@lncf.cnrs-mrs.fr
Ben-Ari
Yehezkel
Y
Gaïarsa
Jean-Luc
JL
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009414:Nerve Growth Factors / Q000502:physiology*; D009473:Neuronal Plasticity; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009414:Nerve Growth Factors; D005680:gamma-Aminobutyric Acid; D011505:Protein-Tyrosine Kinases