Title:
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Investigations into region-specific and activity-dependent gene expression in the mammalian hippocampus
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The hippocampus is a brain region involved in the creation of certain types of memory. The work that contributes to this thesis concerns molecular biological investigations into the functioning of this region and can be divided into two parts. First, the analysis of genes which are restricted in expression to the hippocampus would not only go some way to explain the functional characteristics of this region, but would also provide genetic elements capable of directing spatially restricted expression of transgenes for the purpose of informatively perturbing the formation of memory. A variety of techniques such as degenerate PCR and subtractive hybridisation were therefore applied in an attempt to identify such transcripts. While two novel genes were cloned together with several exhibiting hippocampus-enrichment, none were exclusively expressed in this tissue. Secondly, temporary amnesia occurs in patients who have undergone electroconvulsive therapy as a treatment for severe depression. One potential explanation for this is a saturation of the synaptic plasticity that may underlie memory (known as long-term potentiation or LTP). A subtractive hybridisation technique has been applied to a rat model of this treatment to investigate the possibility that the occlusion of LTP is maintained by long-term changes in hippocampus gene expression; induced gene expression may also be responsible for the anti-depressive effects of this treatment.
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