Determinants of Synaptic Integration in Cerebellar Neurons

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atmire.migration.oldid973
dc.contributor.advisorTurner, Ray W.
dc.contributor.authorEngbers, Jordan David Thomas
dc.date.accessioned2013-05-10T22:09:53Z
dc.date.available2013-11-12T08:00:13Z
dc.date.issued2013-05-10
dc.date.submitted2013en
dc.description.abstractThe integration of synaptic inputs by neurons relies on protein channels that conduct specific ions. Cav3 calcium (Ca2+) channels can amplify excitatory postsynaptic potentials (EPSPs) while Ca2+-activated potassium (KCa) channels decrease EPSP amplitude. By comparison, inhibitory postsynaptic potentials (IPSPs) can activate hyperpolarization-activated (HCN) channels that generate a rebound excitatory current at the end of an inhibitory stimulus. This thesis examines how Cav3, KCa, and HCN channels control synaptic integration in cerebellar Purkinje cells and deep cerebellar nuclei (DCN) neurons. These two populations of neurons are central to cerebellar function and represent a dichotomy of synaptic processing, as Purkinje cells receive primarily excitatory inputs, while DCN neurons receive mainly inhibitory inputs. I tested the hypothesis that Cav3-mediated Ca2+ current activates KCa channels to control the summation of parallel fibre EPSPs in Purkinje cells. Patch clamp recordings from in vitro slices of rat cerebellum showed that Cav3 current activates intermediate conductance KCa (KCa3.1) channels, which have previously never been found in central neurons. KCa3.1 channels are activated at hyperpolarized membrane voltages, due to an extended Cav3 channel window current, and suppress summation of low-frequency EPSPs. Dynamic clamp experiments and computer simulations revealed that the Cav3-KCa3.1 complex increases the signal-to-noise ratio for sensory-like parallel fibre inputs undergoing short-term facilitation by selectively suppressing background inputs. In DCN neurons, I tested the hypothesis that Cav3 and HCN channels control the frequency and timing of rebound bursts following inhibition by IPSPs. The results demonstrate that Cav3 and HCN currents are activated during physiological levels of hyperpolarization and modulate rebound bursts. A novel model of a DCN neuron showed that Cav3 current is solely responsible for generation of the rebound burst, while HCN channels increase burst frequency and temporal precision. Together, this research demonstrates how a novel Cav3-KCa3.1 channel complex participates in the processing of excitatory inputs, and identifies a new synergistic interaction between ion channels that enables processing of inhibitory inputs. These findings illustrate the importance of ion channel interactions for signal processing in the cerebellum, with far reaching implications for neural circuits throughout the brain.en_US
dc.identifier.citationEngbers, J. D. (2013). Determinants of Synaptic Integration in Cerebellar Neurons (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25604en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25604
dc.identifier.urihttp://hdl.handle.net/11023/710
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.subjectPhysiology
dc.subject.classificationCerebellumen_US
dc.subject.classificationPurkinjeen_US
dc.subject.classificationDeep Cerebellar Nucleien_US
dc.subject.classificationCav3 channelen_US
dc.subject.classificationT-typeen_US
dc.subject.classificationKCa3.1en_US
dc.subject.classificationParallel Fibreen_US
dc.subject.classificationHCNen_US
dc.subject.classificationrebound bursten_US
dc.subject.classificationsynaptic processingen_US
dc.titleDeterminants of Synaptic Integration in Cerebellar Neurons
dc.typedoctoral thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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