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Bioinformatics and genetics analysis of experience dependent plasticity in the mouse barrel cortex

Pervolaraki, Eleftheria 2008. Bioinformatics and genetics analysis of experience dependent plasticity in the mouse barrel cortex. PhD Thesis, Cardiff University.

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Formation of neuronal circuits represent memories, making synaptic plasticity the root of learning and memory (Buonomano and Merzenich 1998). Neuronal plasticity has been studied using facial vibrissae deprivation paradigm in rodents (Fox 1992). Whisker deprivation alters the balance of activity in cortical neurons and their responses to sensory input, providing good grounds to study experience dependent plasticity (Simons and Land 1987 Fox 1992). Alterations in gene expression underpinning changes in cortical activity have been investigated in this thesis. The molecular signature underlying the temporal effect of repeated anaesthesia was identified and provided a fertile area for future work, revealing the necessity to separate anaesthesia from deprivation induced changes. Changes in gene expression were gender specific, with the females exhibiting quicker neuronal organisation. Taking under consideration the two confounding factors anaesthesia and gender, a new normalisation protocol was developed underpinning investigations of plasticity dependent transcriptional alterations. The present study confirmed the two molecular mechanisms underlining synaptic plasticity (Shi et al. 1999) with early time points (Day 1) revealing alterations of existing synaptic proteins and later time points (Day 8 and 16) indicating neurotransmitter release regulating gene expression. Day 8 was identified as the critical time point for plasticity, exhibiting the peak of transcriptional changes. Gender specificity was evident, indicating a role for hormonal-dependent gene expression, which future studies should consider. Ontological analysis has confirmed the role of Ca2+ trafficking (via AMPARs and NMDARs) and calcium dependent binding (involving molecules like Calmodulin) in a variety of pathways, such as transporter activity, channel activity and neurogenesis, associated with gene transcription and regulation of plasticity. A significant up-regulation of the expression profiles of transcripts associated with plasticity, NOS1, NOS3 and Bassoon was observed at Day 8 in wild type mice. GluRl-/- mice revealed the direct relationship of these genes with the GluR 1 subunit of AMPA receptors. A delayed up-regulation was detected after 16 days, suggesting a plausible delayed compensatory mechanism in the absence of the GluRl subunit of the AMPA receptor. Gene ontology provided a functional footprint for plasticity even in the GluRl-/- mice, known to exhibit impaired post-synaptic plasticity (Schmitt et al. 2005).

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
ISBN: 9781303218866
Funders: MRC
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:31

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