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The presynaptic protein Mover buffers synaptic plasticity at the hippocampal mossy fiber synapse

dc.contributor.advisorDresbach, Thomas Prof. Dr.
dc.contributor.authorViotti, Julio Santos
dc.date.accessioned2018-03-12T10:12:30Z
dc.date.available2018-03-12T10:12:30Z
dc.date.issued2018-03-12
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-002E-E37F-F
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-6771
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc570de
dc.titleThe presynaptic protein Mover buffers synaptic plasticity at the hippocampal mossy fiber synapsede
dc.typedoctoralThesisde
dc.contributor.refereeMoser, Tobias Prof. Dr.
dc.date.examination2017-11-21
dc.description.abstractengThe increase in the complexity of brains in evolution is accompanied by a surprisingly small number of new synaptic proteins, in particular when considering the remarkably wider range of behavioral responses a primate shows in comparison with a roundworm. However, a few vertebrate-specific synaptic proteins arose. These proteins may convey specialization and complexity to vertebrate nervous systems, for example by increasing vesicle reloading speed, and maintaining or eliminating a synapse. Vertebrate-specific proteins, together with more elaborate circuits, could bridge the gap between simple and complex behaviors. But intricate machineries lead to complicated maintenance and, as a result, malfunctions occur. One of these vertebrate-specific proteins, Synuclein, is involved in Parkinson’s disease. Another one, called Mover, is strongly upregulated in schizophrenia. Mover is a synaptic vesicle-attached phosphoprotein, regulated by activity, and binds the conserved Calmodulin and the vertebrate-specific active zone protein Bassoon. Mover is differentially expressed at subsets of synapses. Knockdown of Mover in the calyx of Held leads to an acceleration of vesicle reloading after synaptic depression and to an increased calcium sensitivity of release. In this study, I have used a Mover knockout mouse line to investigate the role of Mover in the hippocampal mossy fiber to CA3 pyramidal cell synapse and Schaffer collateral to CA1 synapse through extra- and intracellular electrophysiological recordings. While Schaffer collateral synapses were unchanged by the knockout, the mossy fibers showed strongly increased facilitation. The effect of Mover knockout in facilitation was both calcium- and age-dependent, having a stronger effect at higher calcium concentrations and in younger animals. Increasing cAMP levels by forskolin potentiated equally both wildtype and knockout mossy fiber synapses, but occluded the increased facilitation observed in the knockout. Blockade of Kainate receptors also occluded most of the increased facilitation observed in the absence of Mover. These discoveries suggest that a) Mover has distinct roles at different synapses; b) generally acts to dampen the extent of presynaptic events; c) acts as a brake that can be released during low activity. I suggest a model in which Mover inhibits the Kainate receptor/cAMP pathway, which explains the observed results and supports the proposed role of Mover dynamically buffering synaptic strength. The results presented here are discussed in light of a possible role of this vertebrate-specific protein in scenarios such as schizophrenia, epilepsy, superpriming, synaptic plasticity and memory formation.de
dc.contributor.coRefereeMüller, Michael Prof. Dr.
dc.contributor.thirdRefereeNeher, Erwin Prof. Dr.
dc.contributor.thirdRefereeDean, Camin Dr.
dc.contributor.thirdRefereeBrose, Nils Prof. Dr.
dc.subject.engSynapsede
dc.subject.engHippocampusde
dc.subject.engMossy Fiberde
dc.subject.engSchaffer Collateralde
dc.subject.engCA3de
dc.subject.engCA1de
dc.subject.engMoverde
dc.subject.engSynaptic Plasticityde
dc.subject.engFacilitationde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-002E-E37F-F-5
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn1015725643


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