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Title: Investigating the molecular mechanisms underlying recognition memory
Author: Scott , Hannah
ISNI:       0000 0004 5923 8718
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Recognition memory provides us with the ability to judge if we have encountered something before. Communication between the periprhinal cortex (PRh), hippocampus (HPC) and medial prefrontal cortex (mPFC) is essential when associated information needs to be recollected, such as where we have seen an object previously. To investigate the nature of the information flow from the HPC to the mPFC, the direct pathway was selectively inhibited. Intriguingly, this did not affect the rats' performance in an object-in-place task, which suggests that alternative, indirect routes carry information between the two regions. This dissertation further aimed to investigate the mechanisms that regulate gene expression, a process required for the consolidation of long-term recognition memory. Inhibition of DNA methylation in the HPC through infusion of the DNA methyl transferase (DNMT) inhibitor 5-aza-2 -deoxycytidine impaired performance in the object-in-place task with a 24 h delay. No such effect was observed when infusions were made into the mPFC or the PRh. In contrast, infusion of an alternative DNMT inhibitor, RG 1 08 into the PRh impaired both associative recognition memory and familiarity discrimination. The results indicate a role for DNA methylation in the HPC and the PRh in recognition memory and suggest the two DNMT inhibitors may operate through different mechanisms. Lastly, changes in the PRh transcriptome I h after exposure to novel or highly familiar objects were examined using RNA sequencing. Differential gene expression analysis compared to na'ive rats indicated upregulation of transcription factors as well as of genes associated with MAPK and neurotrophin signalling, providing further evidence for an involvement of these cellular processes in recognition memory. Two further genes, Fchol and Gipr, were found to be differentially regulated between rats that had seen novel and those that had explored familiar objects, and may thus represent further factors required for the consolidation of recognition memory.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available