Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574725
Title: Understanding the neurobiology of executive dysfunction in psychiatric disorders
Author: Wallace, Joanne
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2012
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Abstract:
Both schizophrenia and bipolar disorder are characterised by deficits in cognitive function, particularly in those executive functions subserved by the prefrontal cortex. In order to further our understanding of the neuropathophysiology of cognitive deficits in psychiatric disorders, this thesis examined structural and functional changes in the prefrontal cortex (PFC) in rodent models mimicking some aspects of schizophrenia and bipolar disorder. Chosen models were subchronic phencyclidine (PCP), chronic administration of corticosterone to flatten the glucocorticoid rhythm (CORT) and maternal immune activation (MIA). These models mimic glutamate hypofunction, hypothalamo-pituitary adrenal axis dysfunction and maternal infection, respectively. Behavioural studies established that PCP induced a selective deficit in attentional set shifting whilst CORT and MIA induced reversal learning deficits. In vitro electrophysiological studies established a novel model for measuring synaptic transmission in the infralimbic (IL) region of the medial prefrontal cortex (mPFC). Synaptic transmission was shown to be mediated by glutamate and γ-aminobutyric acid (GABA) and to be subject to inhibitory modulation by serotonin (5-HT) and noradrenaline (NA). Differential changes in both basal synaptic transmission and in the monoaminergic modulation of synaptic transmission were evident in the three animal models. Immunohistochemical studies showed that the three animal models induced differential changes in the numbers of particular subtypes of GABAergic interneurones, suggesting that GABAergic activity in the mPFC was altered. These studies demonstrate that models of select features of psychiatric disorders, glutamate hypofunction, HPA axis dysfunction, and prenatal infection, induce deficits in executive function present in psychiatric disorders. These differential behavioural outcomes might be explained by differential changes in synaptic transmission in the mPFC and in the expression of GABAergic interneurones in the mPFC induced in the three models.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.574725  DOI: Not available
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