As mentioned before, the work of this thesis is divided into four chapters, which represent four independent studies that were conducted. They are related by the common theme of synaptic inhibition, which either represented a crucial element in the neuronal processing task that we investigated (Chapter 1, 2 and 4) or we examined the response properties of the inhibitory source (Chapter 3).
Chapter 1:
Glycinergic inhibition has been recently identified to play a crucial role in tuning the ITD sensitivity of MSO neurons (Brand and Grothe 2001, Grothe 2003). However, it is unknown by which mechanism glycine is able to facilitate the ITD tuning. Specifically, it is unclear whether the phase-locked glycinergic inputs interact with the likewise phase-locked excitatory inputs as discrete events or if tonic inhibition is sufficient to explain the observed effects. We addressed this question by performing in vivo extra-cellular recordings from the
MSO of the anesthetized Gerbil. We studied the importance of timing of the endogenous glycinergic inputs by tonic iontophoretical application of glycine or the glycine-antagonist strychnine during the presentation of pure-tone stimuli with varying ITDs. Moreover, by demonstrating a BF-dependency of best ITDs in MSO neurons, the results of this work provide strong evidence for the population-rate-coding model, which has been previously mainly based on data from higher brain centers.
For this study, I performed all MSO recordings and pharmacological experiments except for the subset of experiments of strychnine applications, which were performed by A. Brand and O. Behrend. I performed the data analysis as well as figure design and preparation. The manuscript was written by me and B. Grothe, who also devised the concept of the study and was responsible for the design of the pharmacological experiments.
Chapter 2:
Because of the small size and distant location of the MSO combined with the small action potential sizes and big field potentials surrounding the MSO, in vivo studies on ITD
processing are typically conducted in the IC. However, the level of convergence of inputs from different areas is rather high in the IC, making it difficult to draw direct conclusions about ITD processing in MSO cells. Similar to the IC, DNLL neurons receive direct projections from the MSO, however the level of convergence is supposedly much lower in the DNLL compared to the IC because of the smaller number of input nuclei to the DNLL. By conducting in vivo extra-cellular recordings in the DNLL of anesthetized gerbils, we assessed
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DNLL as a surrogate model nucleus to investigate ITD processing. Subsequently, we indirectly investigated the relative effective timing of inhibition and net excitation in the MSO by recording from DNLL neurons. Also, we collected data on IID sensitivity in low-frequency DNLL neurons and compared this data to the IID sensitivity of the LSO.
The data for this study were obtained by I. Siveke, me, A. Seidl and S. Baudoux. I recorded and analyzed all data on IID sensitive cells. Data analysis on ITD sensitivity was performed by I. Siveke and me. I. Siveke, I and B. Grothe wrote the manuscript. Experimental design was devised by I. Siveke, me and B. Grothe.
Chapter 3:
In this study, we determined physiological properties of MNTB neurons by in vivo extra-
cellular single cell recordings in anesthetized gerbils. In particular, we assessed the range of spontaneous activity rates in MNTB neurons in order to implement these data in subsequent simulations of spontaneous activity in in vitro experiments. This way, we were able to
measure a realistic measurement of recovery times of response adaptation in MNTB cells in vitro. We subsequently compared the obtained values to the recovery times determined in vivo. Moreover, the introduction of spontaneous activity in the in vitro experiments allowed a
re-assessment of the transmission fidelity of the calyx of Held synapse.
I contributed to this study by performing the in vivo experiments and by analyzing most of the in vivo data. In vitro data was obtained and analyzed by J. Hermann. The manuscript was
written by A. Klug and J. Hermann and was revised by me, H. von Gersdorff and B. Grothe. A. Klug, H. von Gersdorff, J. Hermann and I designed the experiments, while A. Klug and B. Grothe devised the study.
Chapter 4:
Here, we examined the potential role of the reciprocal inhibition between the DNLLs on the perceptual suppression of echo directional information. After determining the existence of PI in E/I cells in the gerbil DNLL with in vivo extra-cellular single cell recordings, we assessed
the effects of the DNLL PI on the responses of de novo E/I IC cells to trailing signals with a
physiologically realistic computer model of the auditory brainstem. An ideal observer that relied solely on the output of the model ICs was not only able to identify echoes, but exhibited suppression of echo directional information in a manner that closely agreed with percepts of human subjects that were tested on the same stimuli as the model.
The physiological data was collected by me, B. Saunier-Rebori, I. Siveke, and T. Zahn. The model was designed and built by T. Zahn and I made modifications on the parameter settings and the read-out; I conducted all model simulations. The behavioral experiments were designed by L. Wiegrebe, B. Grothe and me and I conducted these experiments. I
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analyzed the data together with B. Saunier-Rebori, I. Siveke, F. Felmy and A. Klug. The manuscript was written by me, G. Pollak, F. Felmy and B. Grothe. The experiments were designed by G. Pollak, B. Grothe, F. Felmy and A. Klug. T.P. Zahn, B. Saunier-Rebori and I share first authorship for this publication.
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RESULTS
The result section is divided into 4 chapters, of which each chapter represents an independent manuscript that is published in a peer-reviewed international journal.
Chapter 1: Interaural time difference processing in the medial superior olive: the role of
glycinergic inhibition (2008) by Pecka M, Brand A, Behrend O, and Grothe B.
Journal of Neuroscience 28(27):6914-25.
Chapter 2: Binaural response properties of low-frequency neurons in the gerbil dorsal
nucleus of the lateral lemniscus (2006) by Siveke I, Pecka M, Seidl AH, Baudoux S, and Grothe B. Published in the Journal of Neurophysiology
96:1425-1440.
Chapter 3: Synaptic transmission at the calyx of Held under in vivo-like activity levels
(2007) by Hermann J, Pecka M, von Gersdorff H, Grothe B, and Klug A. Published in the Journal of Neurophysiology 98:807-820.
Chapter 4: Inhibiting the inhibition: a neuronal network for sound localization in
reverberant environments (2007) by Pecka M, Zahn TP, Saunier-Rebori B, Siveke I, Felmy F, Wiegrebe L, Klug A, Pollak GD, and Grothe B. Published in the Journal of Neuroscience 27(7):1782-1790.
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CHAPTER 1
Behavioral/Systems/Cognitive