| In the mammalian auditory system, perception of the azimuthal location of a sound is associated with disparities in the timing and level of a sound reaching the two ears: the interaural time difference (ITD) and the interaural level difference (ILD). ITD and ILD information are first encoded in the brainstem nuclei, the medial superior olive (MSO) and the lateral superior olive (LSO), respectively. In the past, it has been assumed that ITD and ILD sensitivity in the brainstem nuclei result from timing and level differences in activities of bilateral afferent inputs. However, several experimental observations suggest that cellular factors may also contribute to encoding ITDs and ILDs in the MSO and LSO. These observations include (1) the rate-ITD sensitivity of an MSO cell depends on sound level (Goldberg and Brown, 1969), which is likely related to level-dependent inhibition; (2) Synaptic inhibition can alter best ITDs in the MSO (Brand et al., 2002); (3) LSO cells show distinct chopper discharge patterns in response to tone-burst stimuli (Tsuchitani and Johnson, 1985), which is likely related to specific membrane properties.;In this thesis, a single-neuron modeling approach is used to provide quantitative explanations for these three observations. Simulations of the level dependence of the ITD sensitivity in the MSO indicate that inhibition adjusts the net excitation input level and allows a cell to maintain a robust ITD-tuning to sound level. Simulations of the shift of the best ITD by inhibition show that the interplay between depolarizing sodium currents and hyperpolarizing inhibitory currents affects the ITD-tuning of an MSO cell. Simulations of the chopper discharge pattern in the LSO indicate that LSO cells are heterogeneous in their membrane properties, and that this heterogeneity leads to differences in their rate-ILD responses and in their sensitivities to envelope-modulated stimuli. Together, the model results lead to the conclusion that ITD and ILD-dependent responses in the MSO and LSO are influenced by their synaptic and membrane properties, which may allow dynamic tuning of the auditory system in natural acoustic environments. Further, model results make testable predictions, which upon experimental testing will enrich our understanding of the neural basis of sound localization. |
