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Title: Genetic and neural changes in zebrafish and how they contribute to different behaviours
Author: Lupton, Charlotte
ISNI:       0000 0004 5921 840X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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How particular neural circuits within the brain control cognition and behaviour is one of the major and yet frequently, unanswerable questions within neuroscience. Over recent years, zebrafish have become an increasingly popular model in which to study behavioural neuroscience due to their vast behavioural repertoire, combined with their ease of recording and manipulation. Recently, two independent genetic systems, the exostosin family of glycosyltransferases, encoded by the EXT genes, and the neuropeptide kisspeptin, encoded by the KISS1 gene, have been implicated in a variety of behaviours within mammals, and more recently, zebrafish (ext and Kiss1 respectively). Abnormalities in exostosin1 in humans (EXT1) has been linked to mental retardation (MR) and austistic-like tendencies in mice (Ext1), whereas, preliminary studies in the zebrafish have suggested defects within aggression. The kisspeptin system is a known regulator of reproduction in a wide variety of mammalian species, and dysfunction leads to variety of manifestations, including infertility. Surprisingly, a recent study has detailed the insignificant role of the kisspeptin system in controlling reproduction in zebafish and instead, another study has linked kisspeptin to aberrations in innate fear after exposure to alarm substance (AS). Inspite of notable findings regarding the behavioural function of the ext2 and Kiss1 genes in zebrafish, an in depth and broader characterization of their function is needed. Using an existing mutant zebrafish line which carries a mutation within the ext2 gene, and robust behavioural assays, I show how heterozygous zebrafish harbouring this mutation, show possible defects in their aggression tendencies, as seen previously, but also within anxiety-like behaviour in the zebrafish. Furthermore, I employed the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology to generate novel mutations within the Kiss1 gene, and its receptor, Kiss1rb. Fish harbouring mutations within kisspeptin 1, were found to have differences compared to control fish in their regulation of fear after exposure to AS. Additionally, mutants also displayed anomalies during the active avoidance paradigm, suggesting that kisspeptin may have a novel role in learning in the zebrafish. In conclusion, this study details the possible differences seen in behaviour following the manipulation of two discrete genetic systems in the zebrafish.
Supervisor: Watt, Penelope J. ; Roehl, Henry ; Jesuthasan, Suresh Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available