GABA(B) and Trk receptor signaling mediates long-lasting inhibitory synaptic depression

In many areas of the nervous system, excitatory and inhibitory synapses are reconfigured during early development. We have previously described the an atomical refinement of an inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive in the developing gerbil a uditory brain stem. Furthermore, these inhibitory synapses display an age-d ependent form of long-lasting depression when activated at a low rate, sugg esting that this process could support inhibitory synaptic refinement. Sinc e the inhibitory synapses release both glycine and GABA during maturation, we tested whether GABAB receptor signaling could initiate the decrease in s ynaptic strength. When whole cell recordings were made from lateral superio r olive neurons in a brain slice preparation, the long-lasting depression o f medial nucleus of the trapezoid body-evoked inhibitory potentials was eli minated by the GABAB receptor antagonist, SCH-50911. In addition, inhibitor y potentials could be depressed by repeated exposure to the GABAB receptor agonist, baclofen. Since GABAB receptor signaling may not account entirely for inhibitory synaptic depression, we examined the influence of neurotroph in signaling pathways located in the developing superior olive. Bath applic ation of brain-derived neurotrophic factor or neurotrophin-3 depressed evok ed inhibitory potentials, and use-dependent depression was blocked by the t yrosine kinase antagonist, K-252a. We suggest that early expression of GABA ergic and neurotrophin signaling mediates inhibitory synaptic plasticity, a nd this mechanism may support the anatomical refinement of inhibitory conne ctions.