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Title: Mechanisms of plasticity in the vestibular system
Author: Guilding, Clare
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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This thesis describes a series of experiments in rat, designed to investigate the underlying molecular causes of VC. The role of the stress systems in the adaptive down-regulation of GABA receptors during compensation is investigated using biochemical and in vitro electrophysiological techniques. The results demonstrate that the down-regulation of GABA receptor efficacy in ipsilesional MVN neurones observed after 4h of compensation following a unilateral labyrinthecytomy (UL) is dependent on activation of glucocorticoid receptors. The enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids from inert forms, and is found to be present in the central vestibulo-oculomotor centres of the brainstem and cerebellum. This suggests that this modulatory enzyme is likely to be involved in regulating the exposure of these centres to circulating glucocorticoids. The results show that the levels of 11β-HSD1 activity in the vestibulo-cerebellum and MVN are stable over the 4h period after UL, disapproving the hypothesis that changes in enzyme modulatory activity may occur in parallel with the deafferentation induced changes in the properties of the ipsilesional MVN over this time. The relative importance of intrinsic membrane properties versus synaptic inputs, to the spontaneous firing rate of ipsilateral MVN neurones is investigated at varying times following UL. The endogenous activity of MVN neurones is assessed by their spontaneous activity recorded in brainstem slices perfused with a cocktail of neurotransmitter antagonists to block synaptic transmission. The results demonstrate a significant increase in excitability of lesioned rostral MVN neurones at 4h post-UL, which is maintained primarily by changes in the intrinsic pacemaker properties of these neurones. At 48h and 1wk post-UL the significant increase in excitability of lesioned rostral MVN neurones is sustained, however by this time it is maintained by an increased excitatory synaptic input onto the neurones. Thus different mechanisms are utilised in the initiation and maintenance of processes involved in VC.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available