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Title: The role of the AMPA receptor subunit GluR1 and nitric oxide in experience-dependent plasticity and memory formation
Author: Dachtler, James
ISNI:       0000 0004 2750 0021
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2010
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Neocortical and hippocampal synaptic long-term potentiation (LTP) initially requires the AMPA receptor subunit GluR1, while late-phase LTP depends upon nitric oxide synthase (NOS). To investigate whether this was relevant to in vivo ED potentiation, GluR1 and/or NOS knockout mice were deprived of all whiskers but the D1 to induce barrel cortex synaptic potentiation, which was quantified by single unit recordings. In deprived cortex, D1 whisker responses potentiated approximately 40% less in GluR1 and NOS3 knockout mice than wild-type mice. Potentiation in the NOS1 knockout was influenced by gender; female NOS1 knockout potentiation was similar to wild-types, yet was absent in male NOS1 knockout mice. The ED potentiation in GluR1 knockout mice was dependent upon NOS, supporting LTP studies. However, NOS1 was more important for potentiation. Thus, while potentiation occurred in the GluR1/NOS3 double knockout mice, it was completely absent in the GluR1/NOS1 double knockout. To determine the interaction between GluR1 and NO activity in memory, behavioural studies examined their impact on spatial and contextual memory. The results partly confirmed earlier findings that retention of contextual fear conditioning was sensitive to GluR1 deletion. However, this was only the case in male GluR1 knockout mice. Female GluR1 KO mice were unimpaired. In a spatial radial arm watermaze task, GluR1 knockout mice acquired the location of a submerged platform more slowly than wild-types. Nevertheless, spatial reference memory was comparable to wild-type mice at the end of training and was not influenced by gender. In contrast to predictions, GluR1-indepdnent reference memory was not dependent upon NOS. Therefore while emotional learning requires GluR1 in male mice, spatial reference memory can form in its absence in both genders and is insensitive to NOS antagonism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available