Voltage gated ion channels shape subthreshold synaptic integration in principal neurons of the medial superior olive

Principal neurons of the medial superior olive (MSO) encode low-frequency sound localization cues by comparing the relative arrival time of sound to the two ears. In mammals, MSO neurons display biophysical specializations, such as voltage-gated sodium (Na[subscript v]) and potassium (K[subscript v]) channels that enable them to detect these cues with microsecond precision. In this dissertation electrophysiological techniques were used to examine the specific channel properties and functional role these channels play in MSO neurons following hearing onset. In addition, computational models that incorporated these physiological data were used to further study how the specific properties of these channels facilitate MSO function. Experiments in this dissertation showed that Na[subscript v] channels are heavily expressed in the persisomatic region of MSO neurons, but unlike those expressed in other neurons they minimally contribute to action potential generation. This is likely due to the low percentage of channels available for activation at the resting membrane potential. Current clamp recordings determined that Na[subscript v] channels counterbalance K[subscript v] channels voltage rectification by boosting near action potential threshold excitatory post-synaptic potentials (EPSPs). Further, computational modeling revealed that synaptic inputs are larger at the soma with Na[subscript v] channels restricted to the soma than when they are evenly distributed throughout the soma and dendrites. During the first few weeks after hearing onset current clamp experiments showed EPSP duration decreased while the temporal resolution for detecting the arrival time of synaptic inputs increased. These changes in EPSP duration are due in part to both the development of faster membrane response properties and increases in the expression of low voltage-activated K[subscript v] channels (K[subscript LVA]). Further investigation determined these channels display a somatically enriched distribution and act to counterbalance the distortions that result from dendritic cable filtering. This is accomplished by K[subscript LVA] actively decreasing the duration of EPSPs in a voltage dependent manner. Computational modeling confirmed these results as well as illustrating their effects on the integration of mono- versus bilateral excitation. Together these findings indicate that the expression of specialized Na[subscript v] and K[subscript v] channels facilitate the neuron’s computational task, detecting and comparing the relative timing of synaptic inputs used in low frequency sound localization.