The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 536-540
Copyright ©2001 by the American Physiological Society

RAPID COMMUNICATION

GABA_B and Trk Receptor Signaling Mediates Long-Lasting Inhibitory Synaptic Depression

 ¹Center for Neural Science and  ²Department of Biology, New York University, New York, New York 10003

Kotak, Vibhakar C., Christopher DiMattina, and Dan H. Sanes. GABA_B and Trk Receptor Signaling Mediates Long-Lasting Inhibitory Synaptic Depression. J. Neurophysiol. 86: 536-540, 2001. In many areas of the nervous system, excitatory and inhibitory synapses are reconfigured during early development. We have previously described the anatomical refinement of an inhibitory projection from the medial nucleus of the trapezoid body to the lateral superior olive in the developing gerbil auditory brain stem. Furthermore, these inhibitory synapses display an age-dependent form of long-lasting depression when activated at a low rate, suggesting that this process could support inhibitory synaptic refinement. Since the inhibitory synapses release both glycine and GABA during maturation, we tested whether GABA_B receptor signaling could initiate the decrease in synaptic strength. When whole cell recordings were made from lateral superior olive neurons in a brain slice preparation, the long-lasting depression of medial nucleus of the trapezoid body-evoked inhibitory potentials was eliminated by the GABA_B receptor antagonist, SCH-50911. In addition, inhibitory potentials could be depressed by repeated exposure to the GABA_B receptor agonist, baclofen. Since GABA_B receptor signaling may not account entirely for inhibitory synaptic depression, we examined the influence of neurotrophin signaling pathways located in the developing superior olive. Bath application of brain-derived neurotrophic factor or neurotrophin-3 depressed evoked inhibitory potentials, and use-dependent depression was blocked by the tyrosine kinase antagonist, K-252a. We suggest that early expression of GABAergic and neurotrophin signaling mediates inhibitory synaptic plasticity, and this mechanism may support the anatomical refinement of inhibitory connections.