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bioRxiv · 10.1101/619783

Presynaptic modulation of inhibitory synaptic feedback via GABAB receptors in the avian cochlear nucleus angularis

Eisenbach, S. L.·Soueidan, S. E.·MacLeod, K. M.
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Abstract

Inhibition plays multiple critical roles in the neural processing of sound. In the avian auditory brain stem, the cochlear nuclei receive their principal inhibitory feedback from the superior olivary nucleus (SON) in lieu of local inhibitory circuitry. In the timing pathway, GABAergic inhibitory feedback underlies gain control to enhance sound localization. In the cochlear nucleus angularis (NA), which processes intensity information, how the inhibitory feedback is integrated is not well understood. Using whole cell patch-clamp recordings in chick brain stem slices, we investigated the effects of GABA release on the inhibitory (presumed SON) and excitatory (8th nerve) synaptic inputs onto NA neurons. Pharmacological activation of the metabotropic GABAB receptors with baclofen profoundly suppressed both evoked excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). Baclofen similarly reduced the frequency of spontaneous IPSCs and EPSCs, but had no significant effect on the current kinetics or amplitudes, indicating a presynaptic locus of modulation. Trains of IPSCs showed substantial transient and sustained short-term synaptic facilitation. Baclofen application reduced the initial IPSC amplitude, but enhanced the relative facilitation over the train via changes in release probability. Comparable levels of GABAB receptor mediated blockade also shifted short-term synaptic plasticity of EPSCs toward less depression. Evoked (but not spontaneous) release of GABA was sufficient to suppress basal release at inhibitory synapses in slices. Overall, the modulation of excitatory and inhibitory inputs of NA neurons via GABAB receptor activation appears to parallel that in the timing pathway.\n\nNew and NoteworthyAvian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity and provide level information for gain control feedback via the superior olivary nucleus. This GABAergic inhibitory feedback was itself modulated in NA via presynaptic, metabotropic GABAB receptor mediated suppression. Excitatory transmission was modulated by the same receptors, suggesting parallel homosynaptic and heterosynaptic mechanisms in both cochlear nuclei.

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Eisenbach, S. L., Soueidan, S. E., MacLeod, K. M.. 2019-05-14. Presynaptic modulation of inhibitory synaptic feedback via GABAB receptors in the avian cochlear nucleus angularis. https://doi.org/10.1101/619783

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