Due to its great importance in learning and memory, the hippocampus has received a lot of attention from studies investigating synaptic plasticity, the molecular correlates of learning and memory. Corticosterone (CaRT) is the endogenous glucocorticoid in rodents and is of high physiological significance to the organism. In response to stress the glucocorticoid concentration rises rapidly, releasing the hormone into the blood and allowing it to exert its actions on the level of the pituitary, the hypothalamus and the hippocampus. Interestingly, learning and memory are also subject to glucocorticoid actions in the hippocampus and the duration of increased glucocorticoid exposure has opposite effects on these measures: while long- term CORT exposure or chronic stress often leads to impairments of learning or memory, short-term CORT exposure has been shown to enhance or facilitate learning and memory. All of these studies have ascribed an important role to the N-methyl-D-aspartate receptor (NMDAR) in modulating CORT-induced changes in synaptic plasticity. Against this background this project aimed at the understanding of rapid CORT-induced effects on synaptic NMDAR-mediated transmission in the rat hippocampus. Using patch-clamp technique it could be shown that CORT rapidly caused an increase in NMDAR-mediated transmission in the hippocampus and that this effect was independent of protein synthesis but dependent on calcium and CaMKII activation. Accordingly, increased levels of phosphorylated CaMKII at its autophosphorylation site Thr286 following CaRT exposure were monitored. Furthermore, increased CaMKII-dependent surface expression of NMDARs following CORT exposure was observed, indicating that CORT induces trafficking of NMDARs. Accordingly, it could be shown that CORT exposure led to an increased association of GluN2B-containing receptors with the motor protein KIF-17. This finding was further corroborated by increased CORT-induced binding of NMDARs to the postsynaptic anchor protein PSD-95. Furthermore, increases in basal NMDAR-mediated transmission were accompanied by changes in the synaptic cluster size of PSD-95 in response to CORT treatment.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:550309 |
| Date | January 2012 |
| Creators | Riedemann, Maria-Therese |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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