Transcriptional Mechanisms Involved in Long-term Potentiation of Hippocampal Neurons

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Embargoed until 2019-03-31
Copyright: Bliim, Nicola
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Abstract
Long-term potentiation (LTP), the persistent strengthening of synaptic connections following high frequency stimulation, is a form of synaptic plasticity proposed to underlie memory formation and consolidation. Despite decades of extensive study our understanding of the molecular mechanisms underpinning LTP remains incomplete. Whilst many of the protein components involved in the mechanisms of LTP have been extensively described the long non-protein-coding RNAs (lncRNAs) remain largely unexplored. Expression of lncRNAs is particularly enriched in the mammalian brain where they potentially impact LTP through regulation of epigentetic processes, transcription, mRNA splicing and translation. Characterisation of all the proteins and lncRNAs involved in LTP may elucidate the molecular mechanisms underlying memory formation and consolidation as well as provide greater insight into perturbation of these processes in developmental and neurodegenerative diseases. This study aimed to comprehensively analyse the transcriptome of primary hippocampal neurons, from neonatal mice, undergoing LTP induction in order to identify and quantify the protein-coding genes and ncRNAs expressed during LTP induction. Furthermore, this project aimed to investigate the transcriptomic changes that result from inhibition of LTP through disruption of synaptic adhesion. Analysis of transcriptome sequencing data led to identification of 64 differentially expressed genes, including four unannotated noncoding lincRNAs, across four distinct LTP conditions. Among those genes four distinct expression patterns could be identified. Gene Ontology (GO) analysis identified numerous enriched GO terms including those associated with intracellular signalling, transcriptional and translational regulation, as well as numerous clusters associated with immune response. The novel unannotated transcripts identified in this study were characterised as putative long intervening non-coding RNAs (lincRNAs), two of which demonstrated potential micropeptide expression. Future studies will determine the role and function of these putative lincRNAs in the induction of LTP. Meta-analysis comparing the results of the present study with those of a recent study on LTP induction in rat hippocampal neurons found no common differentially expressed genes.
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Author(s)
Bliim, Nicola
Supervisor(s)
Janitz, Michael
Sytnyk, Vladimir
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Publication Year
2017
Resource Type
Thesis
Degree Type
Masters Thesis
UNSW Faculty
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