B13 until 12/2013
About project B13 (completed 12/2013)
Project title: The MNTB – an inhibitory hub in theauditory brainstem and its timing
Principal investigators: Lars Kunz, Benedikt Grothe
Summary: For the funding period 2010-2013 we had proposed to study the role of the medial nucleus of the trapezoid body (MNTB) as central inhibitory hub in the brainstem. MNTB neurons target several auditory nuclei involved in precise spatio-temporal auditory processing. To be able to accomplish this function MNTB neurons as well as their sources of inputs show many specializations for fast and high-fidelity processing (e.g. the calyx of Held). In detail, we had proposed to investigate the timing in the MNTB itself and the mechanisms allowing precise temporal information transmission in principle MNTB neurons (e.g. quantification of absolute delays between input and output, solving the problem of contingent failures in action potential firing and the role of inhibitory glycinergic inputs onto MNTB neurons). Furthermore, our studies were intended to provide the basis for related in vivo projects.
To address these questions we had to establish new ways of stimulating MNTB neurons to circumvent a major problem with electric stimulation, the co-stimulation of fibers of passage running through the MNTB and other structures of interest. Light-controlled stimulation using new photo-switchable channel modifiers had been proposed as tools that would allow stimulation of MNTB neurons independently of the fibers of passage. These compounds were provided by the group of D. Trauner (Z3). With the project progressing we realized that the approach using the proposed photo-switchable ligands was not suitable for auditory brainstem neurons due to their low input resistance (5-100 MΩ) and that we thus would have to establish alternative techniques. Though, illuminating neurons incubated with these photo-switchable compounds entailed activation of neuronal activity, these compounds have not shown the properties needed for our model system regarding speed, reversibility and channel specificity <...>