Synaptic Transmission & Signal Representation at the Calyx of Held

The ability to localize the source of a sound plays a vital role for survival and communication in the animal kingdom. While the available timing and loudness cues in this task are often subtle, many species perform it remarkably precise. The underlying neuronal structures have to transmit and represent the auditory information from both ears at high acuity to the centers of sound localization in the brainstem. As part of this pathway the synapses of Held are likely to be specialized for this acuity by their extraordinary size. In my doctorate I investigated whether these synapses accurately transmit the incoming information with respect to its quantity and timing. Further the representation of auditory information was investigated using a recently developed class of nonparametric models, the multilinear models.

We found that action potentials are transmitted faithfully at one type of synapse, the calyx of Held, but not at another type, the endbulbs of Held. To obtain this finding it was necessary to develop a statistical test that can detect the occurrence of failures of transmission under the presence of noise. This method was tested and calibrated using simulated voltage recordings which closely mimicked the real data.

Concerning the timing of synaptic transmission we found that - contrary to previous belief - the delay introduced by synaptic transmission varies as a function of the rate of transmission events at the synapse. Using specialized stimulus paradigms the dynamics of the transmission delay were measured. This allowed us to devise a phenomenological model of the transmission delay which was used to quantify the single spike increases of transmission delay and captured 67\% of the explainable variance. The explainable variance was estimated by simulating the noise induced variability in transmission delay and appropriately correcting the total variance. The changes in transmission delay are large enough to provide constraints for future models of sound localization in following neuronal stages.

Lastly, we investigated the stimulus representation at the calyx of Held, which is useful for modeling the localization of high frequency sounds based on differences in stimulus intensity between the ears. A nonparametric class of models, the multilinear models, was chosen which allows sub-millisecond predictions, flexible regularization, and meaningful interpretation of the parameters. A member of this class, the context model was able to explain 75\% of the explainable variance on average. An important tool in quantifying the model performance is the predictive power whose asymptotic properties were explored formally in some detail. The parameters of the context model also provided some structural insights concerning the sources of inhibition which could be attributed to processes of the inner ear rather than subsequent neuronal interactions.