Abstract

Back in 1907, Lord Rayleigh suggested in his pioneering studies that interaural level differences (ILDs) are used for the localization of high frequency sounds and interaural time differences (ITDs) are used for localization of low frequency sounds (Rayleigh 1907) which was later termed the ‘Duplex theory’ in sound localization. Over the last century, the duplex theory came up against its limits with the presence of ILDs between low frequency sounds in the near-field and ITDs in the envelope of modulated high- frequency sounds. The goal of this doctoral thesis was to further read between the lines of the Duplex theory by studying in study 1 the role of precisely-timed inhibition in the LSO (lateral superior olive), a nucleus in the auditory brainstem of mammals that is equipped to decode ILDs and on the other hand in study 2 to study the role of effective envelope information (created through non-linear cochlear filtering) in low frequency MSO (medical superior olive) neurons, another nucleus in the auditory brainstem of mammals that is well-known for its modulation by ITDs. In the LSO, by disentangling amplitude effects from effects specifically related to input timing, we demonstrate that the timing of inhibition controls spiking with microsecond precision throughout high frequency click trains, resulting in input timing-specific modulation of neuronal output. Furthermore, our data reveal that spiking is facilitated when contralateral inputs are functionally leading excitation within a precise time window. Importantly, our data suggest that post-inhibitory facilitation (PIF) can support ILD maintenance when excitatory inputs are weak. In addition, in vitro whole-cell recordings in mature LSO neurons confirm a reduction in the firing threshold due to prior hyperpolarization giving rise to PIF of otherwise sub-threshold synaptic events. This facilitatory effect based on microsecond precise differences between excitation and inhibition could therefore promote spatial sensitivity of faint sounds. In study 2, since low frequency neurons in the MSO are sensitive to both fine structure and effective envelopes, our goal was to disentangle the contribution of effective envelopes and stimulus fine structure on ITD sensitivity through methodological post-hoc analyses. In order to identify the impact of effective envelopes (ergo the “effective energy” within the spectral content) we presented a battery of frozen broadband noise stimuli at various ITDs. Specifically, these stimuli share the same spectral contents (i.e., same carrier frequencies) but vary in their respective envelopes (i.e., their amplitude fluctuations across the stimulus). Our data reveal that the interplay of effective envelopes and temporal fine structure of the stimulus not only impacts relative spike timing but also dynamically affects overall ITD sensitivity in low frequency MSO neurons. Importantly, each event within the effective envelope that the neuron responds to (i.e., fast energy rise within the relevant sound spectrum with regard to the neuron’s tuning) can contain a unique spectral composition. Since it is unlikely that all four functional inputs to the MSO exhibit identical tuning, the strength of individual functional inputs to the MSO and therefore the underlying coincidence mechanism can vary between events. Interestingly, within each stimulus, we were able to identify specific events where spike timing was neatly matching the temporal displacement of the monaural envelope across ITDs. The findings of this study show that effective envelopes play a crucial role for binaural integration in low frequency MSO neurons with strong evidence for its regulation through pre- and short-time adaptation which suggests that the tuning of relative inputs (inhibition/excitation) could be individually adapted across the stimulus. Specifically, we detected spiking phenomena in MSO neurons that can be attributed to effects of preceding inhibition similar to our findings for the LSO.