Three leaves of erratum inserted inside front cover. / Bibliography: leaves 178-210. / x, 210 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The mature oophorectomised rat is a well-recognised model of post menopausal bone loss, and has been used in this thesis to study the effects of estradiol on bone cells in vivo. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1995

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

In rats, the subnuclei of the inferior olive (IO) and thalamus exist topographic spatial representation to sinusoidal horizontal linear translations along either the antero-posterior or interaural direction. To examine the effect of GABAergic neurotransmission within the vestibular nucleus on the establishment of gravity-related topographic spatial representation in relay station of the central vestibular pathway, GABAA receptor antagonist bicuculline was used to chronically perturb GABA transmission within the vestibular nucleus of postnatal rats. Implantation of bicuculline-loaded or saline-loaded Elvax slice onto the dorsal surface of vestibular nucleus was performed in P1 rats which were allowed to recover into adulthood. Fos protein expression was used as an indicator to identify central neurons responsive to horizontal linear accelerations. In stationary or labyrinthectomized rats, Fos-immunoreactive (ir) neurons were either absent or sporadically scattered throughout the IO and thalamic subnuclei, indicating that the Fos expression in these neural area was otolithic in origin. In the saline control group, Fos expression induced by horizontal antero-posterior linear acceleration was observed in both the IO and thalamus. Responsive IO subnuclei include β subnucleus of IO and dorsomedial cell column while those in the thalamus include central medial nucleus, paracentral nucleus, mediodorsal nucleus, central lateral nucleus, zona incerta and subparafascicular nucleus of thalamus. For-ir neurons responsive to horizontal interaural linear acceleration were found in those IO subnuclei and thalamic subnuclei. When compared with the saline-treated group, the number of Fos-ir IO neurons responsive to horizontal linear acceleration was significantly lower in adult rats perturbed with bicuculline at P1. Besides, the pattern of Fos expression in both the IO and thalamus was altered in adult rats pretreated with bicuculline. In the utricle-related thalamic subnuclei, the postnatal time when Fos-ir neurons were found triggered by otolithic stimulation was delayed and the number of these Fos-ir neurons was fewer in the bicuculline-treated group than those in the saline-treated group. To investigate whether there exists a critical period for postnatal establishment of topographic spatial representation in the IO and thalamus, implantation of bicuculline-loaded Elvax slice onto the vestibular nucleus was carried out in P14 rats. The topographic spatial representation in IO and thalamus of those rats were unchanged as compared with adult rats pretreated with saline at P14. These results indicate that the GABAergic neuronal circuit in the vestibular nucleus plays an important role in postnatal establishment of topographic spatial representation in the central vestibular system. Most importantly, we documented the occurrence of a postnatal critical period (between P1 and P14) during which GABAergic transmission regulated the formation of a gravity-related spatial framework in the brain. / published_or_final_version / Physiology / Master / Master of Philosophy

Vestibular system (VN) is involved in the spatial recognition of animals. Animals with impaired VN were observed with poor spatial navigation abilities. The purpose of this thesis is to study the effect of muscimol on the spatial recognition of rats. It was found that the neonatal diffusion of muscimol to the VN significantly affected the spatial recognition of rats during dead reckoning test. In the light probe test, which distal visual cues were available, the treated rats spent significantly less time searching for the food pellet (student’s t-test: p<0.001). The return time was significantly higher in treated group than the sham control groupwhen they were tested in in the dark probe test (student’s t-test: p<0.001), which animals were limited to idiothetic cues. Similarly, the heading angles were significantly higher in all three different conditions, light/dark probe and new location tests (light: p<0.001; dark: p<0.001; new location: p<0.01). This finding suggests that neonatal diffusion of muscimol affects the development of vestibular nuclei and that thevestibular system is important for the processing of vestibular informationin spatial recognition. / published_or_final_version / Physiology / Master / Master of Medical Sciences

Inhibitory synaptic transmission within the vestibular circuits plays an essential regulatory role in coordinating vestibular functions. The maturation profile of γ- aminobutyric acid (GABA) synapses in the vestibular system remains unknown. To address this, we first used double immunohistochemistry to document the postnatal expression profile of GABAA receptors in canal-related and saccule-related vestibular nuclear neurons of rats. The proportion of Fos / GABAA receptors α1 subunit doublelabeled neurons progressively increased with age. Whole-cell patch-clamp experiments on brainstem slice preparations were also employed to characterize the developmental properties of these synapses within the medial vestibular nucleus. The frequency of GABAA receptor-mediated miniature inhibitory postsynaptic currents (IPSC) progressively increased during the first two postnatal weeks and reached a plateau thereafter. This is in agreement with an increase in sensitivity to GABAA receptor α1 subunit agonist zolpidem during the same period. The rise time and decay time however decreased by 2-fold. These results suggest that change in the composition of GABAA receptor occurs during the functional maturation of medial vestibular neurons. To further investigate whether GABA receptors contribute to synaptic plasticity in the developing vestibular nucleus, two stimulus protocols were used. Repetitive depolarizing pulses induced long-lasting decrease in the frequency of GABAA receptormediated spontaneous IPSCs between P3 and P7. The probability of inducing such frequency decline of sIPSCs decreased after the first postnatal week. High frequency stimulation on the other hand, induced long-term depression (LTD) of GABAA receptormediated evoked IPSCs between P3 and P5. The probability of inducing LTD decreased after P14. These results indicate that LTD at GABAergic synapses could be easily induced in developing medial vestibular neurons before maturation of GABAergic synaptic transmission. To examine if GABAergic transmission within the vestibular nucleus is crucial for establishment of gravity-related spatial organization, an intervention approach was adopted to perturb GABAergic transmission within the postnatal vestibular nucleus. A slice of Elvax loaded with either GABAA receptor agonist muscimol or antagonist bicuculline was inserted into the fourth ventricle and covered the bilateral vestibular nuclei at different ages. Expression of Fos protein in functionally activated neurons was used to demarcate the topographic spatial map in the inferior olive. The spatial map in subnuclei IOβ and DMCC was disturbed in each adult rat that was implanted with bicuculline- or muscimol-loaded Elvax at P1. However, no change was observed in adult rats that were pretreated with bicuculline or muscimol at P14 or P21. Vestibularrelated behavior tests were also performed. The acquisition of negative geotaxis, an otolith-related orientation reflex, was delayed in postnatal rats pretreated with bicuculline but was advanced in those rats pretreated with muscimol. Furthermore, the acquisition of motor learning, evaluated by rotarod test, was impaired in adult rats treated with bicuculline or muscimol. Taken together, our results indicated that maturation of GABAergic transmission within the vestibular nucleus play important roles in development of spatial recognition and vestibular-related behavior. / published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

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Not available / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences