Adolescence as a vulnerable period for the effects of intrinsic and extrinsic regulators of neurogenesis on cognitive behaviour

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dc.contributor.advisor Nolan, Yvonne M. en
dc.contributor.advisor Cryan, John F. en
dc.contributor.advisor O'Leary, Olivia en O'Leary, James Daniel 2018-05-14T11:46:27Z 2018-05-14T11:46:27Z 2017 2017
dc.identifier.citation O'Leary, J. D. 2017. Adolescence as a vulnerable period for the effects of intrinsic and extrinsic regulators of neurogenesis on cognitive behaviour. PhD Thesis, University College Cork. en
dc.identifier.endpage 352 en
dc.description.abstract Postnatal hippocampal neurogenesis is the birth of new neurons within the dentate gyrus that occurs throughout the lifespan. In adulthood, these new neurons have been shown to be necessary for cognitive tasks such as spatial and contextual memory. It is well established that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors, such as intracellular signalling molecules, exercise, inflammation and stress. Moreover, levels of adult hippocampal neurogenesis do not remain constant throughout life. Indeed, levels of hippocampal neurogenesis and integration of new neurons within the dentate gyrus are up to four times higher during adolescence than during adulthood. The first aim of this thesis (addressed in Chapter 2) was to explore the extent and involvement of Tlx in motor, cognitive and anxietyrelated behaviour. A spontaneous deletion of Tlx, a key intrinsic regulator of neurogenesis, was demonstrated to impair motor, cognitive and anxiety-related behaviours during adolescence and adulthood. The second aim of this thesis (addressed in Chapters 3 and 4) was to investigate the impact of adolescent-initiated exercise on hippocampal plasticity and contextual and cued fear conditioning as well as pattern separation in adulthood. It was demonstrated that adult-initiated exercise enhanced both contextual and cued fear conditioning, while conversely, exercise that began in adolescence did not affect performance in these tasks and these differential effects were accompanied by differential expression of plasticity-related genes in the hippocampus in adulthood. Moreover, adult and adolescent-initiated exercise enhanced cognitive flexibility and dendritic complexity of immature neurons in the dentate gyrus. The third aim of this thesis (addressed in Chapter 5) was to examine the impact of chronically elevated IL-1β on adult hippocampal neurogenesis and pattern separation. It was shown that chronic lentiviral-mediated overexpression of IL-1β within the dorsal hippocampus impaired neurogenesis and performance in its associated cognition, while sparing neurogenesis independent cognition. Finally, the fourth aim of this thesis (addressed in Chapter 6) was to explore the impact of chronic IL-1β, chronic unpredictable stress exposure, or a combination of an initial chronic IL-1β insult was examined following exposure to chronic unpredictable stress on learning and memory and depressive-like behaviours. It was shown that exposure to chronically elevated IL1β and chronic stress independently impair certain types of learning and memory and increased depressive-like behaviour. However, exposure to a sequential ‘two-hit’ of chronically elevated hippocampal IL-1β and chronic stress did not produce an exacerbated phenotype. In summary (Chapter 7), disruption of intrinsic regulators of neurogenesis, such as Tlx, or exposure to extrinsic factors, such as exercise or adverse stimuli, like inflammation and stress, and the consequent effect on cognition may provide insight into why adolescence is a vital period for correct conditioning of hippocampal function in later life. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2018, James Daniel O'Leary. en
dc.rights.uri en
dc.subject Cognition en
dc.subject Hippocampus en
dc.subject Touchscreen operant behaviour en
dc.subject Learning and memory en
dc.title Adolescence as a vulnerable period for the effects of intrinsic and extrinsic regulators of neurogenesis on cognitive behaviour en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text available en Not applicable en
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Anatomy and Neuroscience en Medicine en
dc.check.type No Embargo Required
dc.check.reason Not applicable en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Embargo not applicable (If you have not submitted an e-thesis or do not want to request an embargo) en
dc.internal.conferring Summer 2018 en
dc.internal.ricu APC Microbiome Institute en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1537/IE/The nuclear receptor TLX as a cell intrinsic regulator underlying inflammation and stress-induced changes in hippocampal neurogenesis: relevance to cognitive disorders/ en

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© 2018, James Daniel O'Leary. Except where otherwise noted, this item's license is described as © 2018, James Daniel O'Leary.
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