Role of the Cav3-Kv4 Complex in Cerebellar Granule Cells

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atmire.migration.oldid4800
dc.contributor.advisorTurner, Ray
dc.contributor.authorRizwan, Arsalan
dc.contributor.committeememberZamponi, Gerald
dc.contributor.committeememberWhelan, Patrick
dc.date.accessioned2016-08-29T17:26:48Z
dc.date.available2016-08-29T17:26:48Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractThe cerebellum has a simple anatomy and a comparatively small number of neuronal classes connected by clearly defined excitatory and inhibitory projections. The cerebellum is thus an ideal area to study signal processing in neurons and how this behaviour contributes to overall circuit function. A key factor in how the postsynaptic machinery of a neuron converts the information it receives into an output is determined by their intrinsic level of excitability, which in turn determines the pattern or frequency of nerve impulse (spike) discharge. The intrinsic excitability of neurons is determined by the complement of ion channels expressed in the membrane. A low voltage-gated potassium channel of the Kv4 family that is important to regulating spike output in numerous CNS cells is highly expressed in granule cells. The Kv4 channels and low voltage-gated calcium channels of the Cav3 family are known to interact with each other in stellate cells of the cerebellum, whereby the influx of calcium ions enhances the efflux of potassium ions to reduce cell excitability. Thus, any change in the degree of this interaction can fine-tune the role of the Cav3-Kv4 complex in modifying membrane excitability and signal processing via Kv4 channels. This PhD project investigated the hypothesis that the differential expression of a Cav3-Kv4 channel complex and resulting Kv4 availability regulates granule cell excitability, spike output, and learning across the cerebellar lobules. This study used in vitro slices of rat cerebellum to conduct immunocytochemistry and electrophysiological voltage- and current-clamp recordings in the granule cells. Indeed, using immunocytochemistry, this study uncovered differential expression of the Cav3-Kv4 complex across the cerebellar lobules. The electrophysiology work also uncovered key differences in the postsynaptic expression and activity of the Cav3-Kv4 complex between anterior and posterior cerebellum that shapes the processing of mossy fibre input by granule cells. The synaptic plasticity data also revealed a novel NMDAR-mGluR-ERK-Kv4 interplay in cerebellar granule cells that functions to regulate postsynaptic excitability and synaptic responses to mossy fiber input. Overall, this study advances our understanding of the ionic mechanisms that underlie differential signal processing across cerebellar lobules.en_US
dc.identifier.citationRizwan, A. (2016). Role of the Cav3-Kv4 Complex in Cerebellar Granule Cells (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27686en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27686
dc.identifier.urihttp://hdl.handle.net/11023/3228
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.facultyMedicine
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectNeuroscience
dc.subject.classificationCerebellumen_US
dc.subject.classificationIon Channelsen_US
dc.subject.classificationGranule cellsen_US
dc.titleRole of the Cav3-Kv4 Complex in Cerebellar Granule Cells
dc.typedoctoral thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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