| dc.description.abstracteng | The central auditory pathway contains highly specialized giant presynaptic nerve terminals specialized to preserve temporal information carried by acoustic signals (Oertel et al., 1999). One of them, the endbulbs of Held, are large and highly branched axosomatic endings arising from auditory nerve fibers that converge onto bushy cells in the anterior ventral cochlear nucleus (AVCN). In addition, bushy cells receive a number of inhibitory inputs from of non-cochlear origin. The vertebrate-specific presynaptic protein Mover was identified as an interaction partner of the active zone protein Bassoon and suggested to have a regulatory role in the control of release probability (Pr) (Kremer et al., 2007; Körber, 2011). Based on these findings the present study aimed to further investigate the localization and role of Mover with a particular focus endbulbs of Held. Mover immunofluorescence signals of Mover were present at endbulbs of Held as well as at inhibitory synapses around bushy cells. Mean fluorescence intensities of Mover signals in endbulbs of Held were broadly distributed over different cells but were similar between converging endbulbs onto one bushy cell providing an, albeit indirect, correlation between the Mover level and Pr which support the suggestion for the role of Mover in regulation of Pr. In order to study whether Mover is regulated by activity in auditory nerve fibers (ANF) Mover fluorescence intensities were compared in wild-type and knock-out Otoferlin mice, the latter one are lacking activity in ANF. A reduction of Mover fluorescence intensities by 35% was found indicating an activity dependent regulation of Mover in endbulbs of Held. To further elucidate the role of Mover a Mover knock-out mouse as generated. Using electrophysiology and patch clamp recordings from bushy cells in auditory brainstem slices the synaptic transmission at the endbulbs of Held in Mover knock-out animals was studied. Analysis of spontaneous miniature excitatory postsynaptic currents (mEPSCs) revealed an increased quantal size and area of mEPSCs in Mover knock-out animals. However, kinetics of mEPSCs remained unchanged suggesting that the amount of AMPA receptor is increased. Yet, further experiments have to be performed to study the consequences of these changes for synaptic transmission upon evoked action potentials. | de |