Dr. Eckhard Friauf

NP05:
Prof. Dr. Eckhard Friauf

L-VGCC subtypes during development of inhibitory and excitatory circuitry in the central auditory system.

University of Kaiserslautern, Germany

We can demonstrate a long-lasting research expertise in the development of the central auditory system of mammals. Our research focuses on the analysis of the development of auditory brainstem structure and function. The emphasis of our work is laid on the superior olivary complex, where input from the two ears converges for the first time in the central auditory system. This binaural input is analyzed to localize sound sources in space. One unique feature of the system is the anatomical organization of the inputs, which are excitatory from the ipsilateral ear and inhibitory from the contralateral ear. The postsynaptic elements in the lateral superior olive thus compute interaural intensity differences. The topography of the inputs is exquisite, i.e., the cochleotopic frequency map is very precisely maintained in both inputs, and neurons with the same characteristic frequency terminate on the same postsynaptic target neuron. Exact axonal target finding and synapse stabilization and refinement ultimately lead to the exquisitely tuned microcircuitry. How the exquisite organization is achieved during development is still unclear. Previous work in our group has demonstrated that the inhibitory, glycinergic input is excitatory during early development when synapse maturation occurs. The transiently excitatory input triggers Ca2+ influx which is mediated through L-VGCCs. The Ca2+ influx is thought to provide a trophic s ignal that leads to the activity-dependent augmentation and stabilization of the synapses. When the microcircuitry is maintained in organotypic slice cultures, activation of L-VGCCs is required to keep the system alive, pointing to the vital importance of these Ca2+ channels. Within this network, we want to specify the role of individual members of the L-VGCCs for development and maintenance of inhibitory microcircuits.

The methodological repertoire of our team covers electrophysiology and optical recordings with voltage-sensitive dyes in brain slices, neurohistological techniques such as immunohistochemistry and in situ hybridization, proteomic approaches (2D-gel electrophoresis and mass spectrometry), and state-of-the-art molecular biology (RT-PCR and large-scale gene expression analyses). Training will be provided to the NPs in all of these methodologies. Training of graduate students in research activities is a major aspect of our team. We contribute to the education in biology, biochemistry, and biophysics. Training is provided in small groups directly at the research setups, allowing intensive hands-on practice. Our team participates in the Graduate Research School "Cellular membrane transport" which is a major focus of our graduate program. Weekly journal clubs, progress reports, and discussion groups are all being held in English and train extensively in soft skills. The 'International School of Graduate Studies' at our university provides an umbrella organization for all PhD students.

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L-type calcium channels in health and diseaseknipper@uni-tuebingen.de