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This dissertation, Maturation Profile of GABA-ergic Inhibition in the Vestibular Nucleus: Role in Developmental Plasticity and Spatial Recognition by Huijing, Hu, 扈慧静, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: 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, evaluat

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