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 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.
Kotak
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Center for Neural Science, New York University, New York, New York 10003, USA.
DiMattina
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Sanes
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005849:Gerbillinae; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018080:Receptors, GABA-B / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D019208:Brain-Derived Neurotrophic Factor; D018755:GABA Agonists; D018756:GABA Antagonists; D009025:Morpholines; D018080:Receptors, GABA-B; D017475:Receptors, Nerve Growth Factor; D001418:Baclofen