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

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Abstract
In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent long-term potentiation (LTPGABA-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 GABAA 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 LTPGABA-A. The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTPGABA-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 LTPGABA-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 LTPGABA-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.