Show simple item record

dc.contributor.authorVickers, Catherine Anneen
dc.date.accessioned2018-01-31T11:39:22Z
dc.date.available2018-01-31T11:39:22Z
dc.date.issued2005en
dc.identifier.urihttp://hdl.handle.net/1842/27580
dc.description.abstracten
dc.description.abstractThe major receptor for excitatory neurotransmission in the central nervous system is the n-methyl-D-aspartate (NMDA) receptor. Previous work has shown this receptor to be important in development, synaptic plasticity, learning and memory, and ischaemia. Studies have shown that this receptor can be linked to networks of signalling proteins through binding to a scaffolding protein Postsynaptic Density Protein 95 (PSD-95). This complex of proteins is termed the NMDA receptor complex (NRC). This thesis examined the role of PSD-95 in excitatory signalling and synaptic plasticity in several areas of the brain, with particular focus on the corticostriatal system. A combination of anatomical, biochemical and electrophysiological techniques were used to address this central question. Previous work in the laboratory had reported a localised increase in dendritic spine density in mice with a mutation in PSD-95. Anatomical analysis of striatal neurones revealed a decrease in spine density along the dendrites in mice with mutated PSD-95. Further to this, experiments addressed the role of PSD-95 in corticostriatal synaptic plasticity. Electrophysiological recordings from striatal spiny cells revealed no strong phenotype in the PSD-95 mutant mouse with regard to alterations in excitatory postsynaptic potential (EPSP) amplitude post trains of cortical stimulation. However, there was significant increase in the duration of the EPSPs in the PSD-95 mutants with respect to wild type. In the final set of experiments, a proteomic approach was used to assess the expression levels of proteins in the NRC in specific regions of the mouse brain in wild type and PSD-95 mutants. Analysis revealed there to be no difference in expression levels of associated proteins within the forebrain (striatum, hippocampus and cortex) of wild type animals, but that the cerebellum showed expression levels that differed to the other areas. However, analysis of mice with a mutation in PSD-95 revealed there to be alterations in the expression levels and phosphorylation states of NRC associated proteins. These proteins were altered throughout the forebrain regions analysed, along with the cerebellum. They included proteins known to be important in NMDA receptor dependant signalling and synaptic plasticity. Moreover, analysis of expression levels of specific NRC associated proteins believed to have roles in global ischaemia, revealed further alterations in PSD-95 mutant mice that had been subjected to global ischaemia.en
dc.description.abstractThe data reported in this thesis address the roles of PSD-95 in excitatory signalling. The data reveal that PSD-95 is important in several aspects of neuronal connectivity, but that its effects can be specific to different areas of the brain. Moreover, the data suggest that the removal of an important protein from a signalling network can affect other signalling molecules within the same network.en
dc.publisherThe University of Edinburghen
dc.relation.isreferencedbyAlready catalogueden
dc.subjectAnnexe Thesis Digitisation Project 2017 Block 16en
dc.titleThe role of postsynaptic density protein 95 (PSD-95) in excitatory signallingen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelen
dc.type.qualificationnamePhD Doctor of Philosophyen


Files in this item

This item appears in the following Collection(s)

Show simple item record