Date

2013

Document Type

Dissertation

Degree

Doctor of Philosophy

Department

Integrative Biology

First Adviser

Burger, R. Michael

Other advisers/committee members

Lu, Yong; Falk, Matthias; Haas, Julie

Abstract

Sound localization is a critically important task for many animals including humans. Due to physical constraints acting on the circuits that process sound localization cues, many neural specializations have evolved. One of the key features and the focus of this dissertation is inhibitory input. To assess the impact of inhibition, I employ in vitro patch clamp techniques to observe cellular and synaptic physiology in brainstem circuits dedicated to sound localization processing. Using a mammalian model, I test the impact that GABAB receptor (GABABR) activation has on the inputs to the medial superior olive (MSO), the first area where sound localization computations take place. Activation of GABABRs modulates both excitatory and inhibitory inputs such that the magnitude of these inputs is decreased and the time course of inhibitory inputs is slowed. The functional significance of this modulation was tested using a bilateral stimulation protocol, which simulates the coincidence of in vivo excitatory inputs. Here, activation of GABABRs increased the sensitivity of MSO neurons to simulated interaural time disparity (ITD), the main cue for low frequency sound localization. To expand on these results, a computational model was used to show that each GABABR dependent modulation had a beneficial impact on ITD sensitivity in the MSO. In an avian system, I described the synaptic activity involving the superior olivary nucleus (SON), which provides the main inhibitory input in the avian sound localization circuit. At the SON itself, synaptic transmission consists of both GABA- and glycinergic components where glycine release is the result of co-release with GABA. I also show that functional glycine receptors localize at brainstem nuclei and that high frequency stimulation results in the release glycine onto nucleus magnocellularis neurons, a feature of the avian brainstem that has not been observed previously. In related experiments, I evaluate possible interactions that may occur when both GABA and glycine receptor systems are activated simultaneously. Here, a pre-activation of GlyRs leads the a decrease in conductance through the GABAAR likely due to changes in Cl- ion concentrations which manipulate the driving force of the ion.

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