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postgraduate thesis: Regulatory role of perineuronal chondroitin sulfates and semaphorin 3A in developing vestibular circuitry

TitleRegulatory role of perineuronal chondroitin sulfates and semaphorin 3A in developing vestibular circuitry
Authors
Issue Date2017
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Kwan, P. [關佩宜]. (2017). Regulatory role of perineuronal chondroitin sulfates and semaphorin 3A in developing vestibular circuitry. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.
AbstractPerineuronal nets (PN) are implicated in restricting neural plasticity with the maturation of neural circuits. Our study of the central vestibular nucleus (VN) found consolidation of PN around GABAergic interneurons, especially the parvalbumin-expressing ones, as from postnatal day (P)9 of Sprague Dawley (SD) rats. This was accompanied by progressive localization of semaphorin 3A (Sema3A) to chondroitin sulfate moieties (CS) of PN. We hypothesized that PNCS binding of Sema3A limits the action of Sema3A as a plasticity-inducing factor in the VN. We tested for structural plasticity in VN explant cultures following treatment with chondroitinase ABC (ChABC) and/or Sema3A. Time-lapse video recording of explant cultures and timed fixation of parallel cultures were assessed for neurite arborization and growth. Compared with null treatment controls, increase in these parameters suggested involvement of CS and Sema3A in controlling structural plasticity of VN neurons in the growth phase. To find if PN-CS/Sema3A bears behavioral consequences, the rats were assessed for developmental emergence of negative geotaxis and air-righting as read-outs of the maturation of the circuit for graviception. ChABC/Sema3A treatment of the rat VN at P6 resulted in delayed display of both negative geotaxis and air-righting. The delay notably correlated with postponed formation of PN after ChABC treatment, revealing that PN consolidation around VN interneurons is a key step in the maturation of the vestibular circuitry for graviception. To find if PN-CS/Sema3A impacts on pre- or postsynaptic events at the circuit level, whole-cell patch-clamp recordings of miniature excitatory post-synaptic AMPA receptor-mediated current (mEPSC) from VN interneurons was performed in brainstem slice preparations of P7/P9 rats following control versus test treatment with ChABC/Sema3A in the VN of P6 rats. We found significant increase in frequency, but not in amplitude of mEPSCs by P9, following the test treatment. Together with the enhanced trafficking and presentation of GluA2-containing AMPAR at the surface of neurons as observed following ChABC/Sema3A treatment in culture, the results suggest plasticity triggered by sema3A at excitatory synapses onto otherwise PN-enwrapped PV-neurons in the VN circuit. Our results provide evidence for the role of PN-CS-Sema3A in controlling structural and circuit plasticity at the interneuron level with impacts on the developmental display of graviceptive behaviour.
DegreeDoctor of Philosophy
SubjectChondroitin sulfates
Semaphorins
Vestibular nuclei
Dept/ProgramBiomedical Sciences
Persistent Identifierhttp://hdl.handle.net/10722/257614

 

DC FieldValueLanguage
dc.contributor.authorKwan, Pui-yi-
dc.contributor.author關佩宜-
dc.date.accessioned2018-08-08T06:35:28Z-
dc.date.available2018-08-08T06:35:28Z-
dc.date.issued2017-
dc.identifier.citationKwan, P. [關佩宜]. (2017). Regulatory role of perineuronal chondroitin sulfates and semaphorin 3A in developing vestibular circuitry. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR.-
dc.identifier.urihttp://hdl.handle.net/10722/257614-
dc.description.abstractPerineuronal nets (PN) are implicated in restricting neural plasticity with the maturation of neural circuits. Our study of the central vestibular nucleus (VN) found consolidation of PN around GABAergic interneurons, especially the parvalbumin-expressing ones, as from postnatal day (P)9 of Sprague Dawley (SD) rats. This was accompanied by progressive localization of semaphorin 3A (Sema3A) to chondroitin sulfate moieties (CS) of PN. We hypothesized that PNCS binding of Sema3A limits the action of Sema3A as a plasticity-inducing factor in the VN. We tested for structural plasticity in VN explant cultures following treatment with chondroitinase ABC (ChABC) and/or Sema3A. Time-lapse video recording of explant cultures and timed fixation of parallel cultures were assessed for neurite arborization and growth. Compared with null treatment controls, increase in these parameters suggested involvement of CS and Sema3A in controlling structural plasticity of VN neurons in the growth phase. To find if PN-CS/Sema3A bears behavioral consequences, the rats were assessed for developmental emergence of negative geotaxis and air-righting as read-outs of the maturation of the circuit for graviception. ChABC/Sema3A treatment of the rat VN at P6 resulted in delayed display of both negative geotaxis and air-righting. The delay notably correlated with postponed formation of PN after ChABC treatment, revealing that PN consolidation around VN interneurons is a key step in the maturation of the vestibular circuitry for graviception. To find if PN-CS/Sema3A impacts on pre- or postsynaptic events at the circuit level, whole-cell patch-clamp recordings of miniature excitatory post-synaptic AMPA receptor-mediated current (mEPSC) from VN interneurons was performed in brainstem slice preparations of P7/P9 rats following control versus test treatment with ChABC/Sema3A in the VN of P6 rats. We found significant increase in frequency, but not in amplitude of mEPSCs by P9, following the test treatment. Together with the enhanced trafficking and presentation of GluA2-containing AMPAR at the surface of neurons as observed following ChABC/Sema3A treatment in culture, the results suggest plasticity triggered by sema3A at excitatory synapses onto otherwise PN-enwrapped PV-neurons in the VN circuit. Our results provide evidence for the role of PN-CS-Sema3A in controlling structural and circuit plasticity at the interneuron level with impacts on the developmental display of graviceptive behaviour. -
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.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject.lcshChondroitin sulfates-
dc.subject.lcshSemaphorins-
dc.subject.lcshVestibular nuclei-
dc.titleRegulatory role of perineuronal chondroitin sulfates and semaphorin 3A in developing vestibular circuitry-
dc.typePG_Thesis-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineBiomedical Sciences-
dc.description.naturepublished_or_final_version-
dc.date.hkucongregation2017-
dc.identifier.mmsid991043982881003414-

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