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dc.contributor.advisor Moser, Tobias Prof. Dr. de
dc.contributor.author Mendoza Schulz, Alejandro de
dc.date.accessioned 2013-06-20T08:10:11Z de
dc.date.available 2013-06-20T08:10:11Z de
dc.date.issued 2013-06-20 de
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-0020-5E42-8 de
dc.language.iso eng de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc 570 de
dc.title The role of the presynaptic scaffold protein Bassoon in synaptic transmission at the mouse endbulb of Held synapse de
dc.type doctoralThesis de
dc.contributor.referee Moser, Tobias Prof. Dr. de
dc.date.examination 2013-06-07 de
dc.description.abstracteng Endbulbs of Held are large calyceal presynaptic terminals of auditory nerve fibers driving bushy cells in the AVCN. These synapses transmit precisely timed auditory signals up to high frequencies that provide the basis for downstream computation of sound localization and for speech perception (Oertel, 1997, 2005). The underlying molecular mechanisms in these ultrafast processes are largely unknown. The presented study analyzed functional and structural changes upon genetic disruption of bassoon, a large presynaptic scaffold protein in the cytomatrix of the active zone by studying the partial deletion mutant Bsn∆Ex4/5 (Altrock et al., 2003). Piccolo expression at active zones was upregulated, and RIM2 and Munc13-1 remained present at mutant active zones. Endbulb terminal and active zones were normal in number; however, postsynaptic densities (PSDs) were enlarged and the vesicle number in close proximity to the presynaptic plasma membrane per µm PSD reduced. In in vitro electrophysiological experiments in auditory brainstem slices, bushy cell miniature EPSCs exhibited larger amplitudes with unchanged kinetics. By applying a minimal stimulation technique, the amplitude of evoked EPSCs recorded from bushy cells was found unaltered while EPSC kinetics was attenuated. Short-term depression in response to train stimulation was increased in the mutants; most pronounced at 100 Hz compared to 200 Hz and 333 Hz. These findings and a reduced rate of recovery after short-term depression suggest that the rate of vesicle replenishment is compromised in the absence of full-length bassoon. The size of the readily releasable pool of vesicles was reduced and release probability was increased as estimated with the method of cumulative EPSCs (Schneggenburger et al., 1999). In consequence, delayed/asynchronous release was increased in the mutant synapses during and after train stimulation. Even though synaptic depression was significantly stronger in mutant synapses, bushy cells compensated for the loss of input and fired with comparable reliability during high frequency stimulation. Auditory brainstem responses from bassoon mutants show synchronous activity from globular bushy cells (as indicated by almost normal wave 2) despite almost complete lack of synchronous activity in the auditory nerve (Khimich et al., 2005; Buran et al., 2010). Additionally to convergence that presumably contributes to this process, restoration of synchronous activity at the level of the AVCN is due to homeostatic plasticity in bushy cells encompassing increased intrinsic excitability and synaptic upscaling. This is manifest in increased mEPSC amplitudes and an enhanced response to depolarizing current injection in mutant bushy cells. In conclusion, the data reported here suggest that bassoon plays an important role in promoting vesicular replenishment and a large standing readily releasable pool. Moreover, bushy cells maintain reliability of transmission in a homeostatic fashion in response to partial auditory deprivation. de
dc.contributor.coReferee Neher, Erwin Prof. Dr. de
dc.subject.eng Bassoon de
dc.subject.eng endbulb of Held de
dc.subject.eng vesicular replenishment de
dc.subject.eng cytomatrix of the active zone de
dc.subject.eng synaptic transmission de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-0020-5E42-8-2 de
dc.affiliation.institute Biologische Fakultät für Biologie und Psychologie de
dc.subject.gokfull Biologie (PPN619462639) de
dc.identifier.ppn 749872675 de

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