| dc.contributor.advisor | Dresbach, Thomas Prof. Dr. | |
| dc.contributor.author | Pofantis, Ermis | |
| dc.date.accessioned | 2019-10-10T09:48:33Z | |
| dc.date.available | 2020-04-09T22:50:02Z | |
| dc.date.issued | 2019-10-10 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0005-126D-D | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-7598 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Mover affects a subpool of primed synaptic vesicles in the mouse calyx of Held | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Brose, Nils Prof. Dr. | |
| dc.date.examination | 2019-04-11 | |
| dc.description.abstracteng | Neuronal communication is a complex process; synapses must be formed, neurotransmitter has to be released at precise time points and it has to be “sensed” by the receiving end of a synapse with an equal accuracy. In this highly coordinated ballet of proteins any change may result in disharmony and eventually in pathology. Therefore, any new addition during the course of evolution must be fulfilling a specific purpose. A relatively new protein in the evolutionarily highly-conserved presynaptic apparatus, since it is vertebrate specific, is Mover. It is attached to synaptic vesicles and interacts with Calmodulin and Bassoon, another vertebrate-specific active zone protein. Mover’s expression levels vary throughout the brain, suggesting a modulatory function at the operation of the synapses.
Here, I aimed to elucidate Mover’s role in synaptic transmission in the calyx of Held, a central glutamatergic synapse, using a Mover knockout (ko) mice. To this end, I recorded spontaneous and evoked excitatory postsynaptic currents (epscs) from brainstem slices using a whole-cell patch clamp configuration.
In the ko evoked epscs were slightly smaller, and took longer to reach the same steady-state levels as the wild-type upon high frequency stimulation. Applying a blind-source separation technique termed non-negative tensor factorization allowed me to distinguish between different subpools of vesicles. This analysis gave rise to a model in which the absence of Mover reduces the release probability of a subpool of vesicles, termed “tight-state” vesicles –referring to the conformation of the snare complex and its associated proteins. Additionally, the size of this pool is significantly increased, indicating a compensatory mechanism. In contrast, the loose-state synaptic vesicles, the functional precursors of the tight-state ones, are unaffected by the absence of Mover.
These findings suggest that Mover modulates the initial release probability, by specifically influencing the subpool of these tight-state vesicles. | de |
| dc.contributor.coReferee | Moser, Tobias Prof. Dr. | |
| dc.contributor.thirdReferee | Neher, Erwin Prof. Dr. | |
| dc.contributor.thirdReferee | Dean, Camin Ph.d. | |
| dc.contributor.thirdReferee | Pardo, Luis A. Dr. | |
| dc.subject.eng | neuroscience | de |
| dc.subject.eng | biology | de |
| dc.subject.eng | synaptic transmission | de |
| dc.subject.eng | synaptic plasticity | de |
| dc.subject.eng | calyx of Held | de |
| dc.subject.eng | presynapse | de |
| dc.subject.eng | Mover | de |
| dc.subject.eng | synaptic priming | de |
| dc.subject.eng | superpriming | de |
| dc.subject.eng | presynaptic proteins | de |
| dc.subject.eng | brain | de |
| dc.subject.eng | mouse | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-126D-D-0 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.description.embargoed | 2020-04-09 | |
| dc.identifier.ppn | 1678722685 | |