Cellular and Network Substrates of Neuronal Excitability in Relation to Epileptic Seizures

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dc.contributor.advisorZamponi, Gerald W.
dc.contributor.advisorFederico, Paolo
dc.contributor.authorKhosravani, Houman
dc.date.accessioned2016-01-30T21:04:15Z
dc.date.available2016-01-30T21:04:15Z
dc.date.issued2007-07
dc.descriptionBibliography: p. 166-208en
dc.description.abstractBrain function is, in part, maintained by an appropriate balance between excitatory and inhibitory elements. In relation to excitability, factors such as the complement and distribution of ion channels, properties and composition of synaptic proteins, and dynamics affecting network synchrony all interact to modulate neuronal firing and network activity. In this dissertation, I present a series of three focused studies at the level of ion channels (T-type calcium channels), synaptic transmission (prion protein), and network activity (high frequency oscillations) that affect neuronal excitability. With regards to Cav3.2 T-type voltage-gated calcium channels, I demonstrate that novel missense mutations, as identified in patients with idiopathic generalized epilepsies, can result in alteration of channel biophysical properties. The majority of mutants altered gating properties consistent with greater channel activity. However, most of these biophysical alterations were not large in magnitude suggesting that the role of these channels in relation to other cellular processes may be affected. At the level of synapses, I describe a novel interaction/modulation of NMDA receptor currents by the endogenous prion protein (PrP). Using PrP-null mice, I show that loss of PrP results in enhanced synaptic NMDA currents with greater amplitude and prolonged deactivation kinetics. These changes do not seem to be related to developmental effects and possibly involve an NMDA receptor subunit switch to functional receptors containing NR2D. At the network level, I show that high frequency oscillations in field recordings in vitro and in the EEG from patients with epilepsy are localized to the seizure onset zone and increase over time during the immediate pre-seizure period. This knowledge can be used to better localized seizures for surgical resection, thereby improving seizure control in intractable patients. These three topics and their relevance to hyperexcitable states are discussed in the context of epileptiform seizure activity and neurological disease.en_US
dc.format.extentxii, 208 leaves : ill. ; 30 cm.en
dc.identifier.citationKhosravani, H. (2007). Cellular and Network Substrates of Neuronal Excitability in Relation to Epileptic Seizures (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/15505en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/15505
dc.identifier.urihttp://hdl.handle.net/1880/51068
dc.language.isoeng
dc.publisher.facultyGraduate Studies
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.titleCellular and Network Substrates of Neuronal Excitability in Relation to Epileptic Seizures
dc.typedoctoral thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 2126 627942996
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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