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postgraduate thesis: Maturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognition

TitleMaturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognition
Authors
Issue Date2011
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Hu, H. [扈慧静]. (2011). Maturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4729733
AbstractInhibitory 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.
DegreeDoctor of Philosophy
SubjectGABA - Receptors
Vestibular nuclei
Neurons
Rats - Physiology
Dept/ProgramPhysiology
Persistent Identifierhttp://hdl.handle.net/10722/208424

 

DC FieldValueLanguage
dc.contributor.authorHu, Huijing-
dc.contributor.author扈慧静-
dc.date.accessioned2015-03-09T02:47:48Z-
dc.date.available2015-03-09T02:47:48Z-
dc.date.issued2011-
dc.identifier.citationHu, H. [扈慧静]. (2011). Maturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognition. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4729733-
dc.identifier.urihttp://hdl.handle.net/10722/208424-
dc.description.abstractInhibitory 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.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshGABA - Receptors-
dc.subject.lcshVestibular nuclei-
dc.subject.lcshNeurons-
dc.subject.lcshRats - Physiology-
dc.titleMaturation profile of GABA-ergic inhibition in the vestibular nucleus : role in developmental plasticity and spatial recognition-
dc.typePG_Thesis-
dc.identifier.hkulb4729733-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplinePhysiology-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4729733-
dc.date.hkucongregation2011-

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