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

Abstract

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 brainderived 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.

Developmental Plasticity of Inhibitory Circuitry

“…Mechanisms that may underlie inhibitory plasticity will be discussed, including the possibility that it is limited to the early period when GABA/glycine release is excitatory (BenAri, 2002) or that corelease of another substance alters synapses that produce inhibition (Gillespie et al, 2005). Alternatively, inhibitory synapses may decline in strength through long-term depression (Kotak et al, 2001;Chang et al, 2003), or an as-yet undiscovered mechanism may be responsible. Whatever the mechanism, it is clear that inhibitory plasticity plays an important role in activity-dependent modification of developing circuits.…”

The Mammalian Interaural Time Difference Detection Circuit Is Differentially Controlled by GABAB Receptors during Development

“…Several days after hearing onset, GABA B R activation does not alter postsynaptic conductances. However, as indicated by the intracellular GABA B R immunoreactivity, these receptors might be involved in long-term changes of synaptic efficacy (Kotak et al, 2001;Yevenes et al, 2003).…”

“…Presynaptically situated GABA B Rs modulate the release probability of inhibitory and excitatory neurotransmitters by depressing Ca 2ϩ currents (Wojcik and Neff, 1984;Isaacson, 1998;Takahashi et al, 1998). Additionally, GABA B Rs can be indirectly involved in long-term plastic changes of synaptic efficacy (Kotak et al, 2001;Kamikubo et al, 2007). In the mature auditory brainstem, GABA B Rs primarily contribute to the dynamic regulation of transmitter release.…”

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

“…The pathway through which this Ca 2ϩ rise is translated into long-term changes of synaptic efficacy involves the activation of protein kinases (Kano and Konnerth, 1992;Kano et al, 1996). Although a considerable body of evidence indicates that brain-derived neurotrophic factor (BDNF) and associated protein tyrosine kinases (PTKs) contribute to the induction of glutamatergic LTP (O'Dell et al, 1991;Grant et al, 1992;Huang and Hsu, 1999), little is known about their possible role in the induction and/or maintenance of synaptic plasticity at inhibitory synapses (Kotak et al, 2001).…”